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Abbott and Enanta Announce Advancement of Hepatitis C Collaboration
Initiation of Phase 2 Clinical Trial Investigating Three Individual HCV Antivirals
ABBOTT PARK, Ill. and WATERTOWN, Mass., March 2
ABBOTT PARK, Ill. and WATERTOWN, Mass., March 2 /PRNewswire-FirstCall/ -- Abbott (NYSE: ABT) and Enanta Pharmaceuticals announced today the advancement of their Hepatitis C (HCV) collaboration into Phase 2 clinical trials. The trial will evaluate three HCV antiviral agents, including the investigational protease inhibitor ABT-450, part of the Abbott-Enanta collaboration, and polymerase inhibitors ABT-333 and ABT-072 currently being developed exclusively by Abbott. Each antiviral agent will be dosed individually in combination with the current standard of care (SOC).
ABT-450 was discovered as part of an alliance between Abbott and Enanta. ABT-333 and ABT-072, both discovered internally at Abbott, are part of the company's ongoing non-nucleoside polymerase inhibitor development program.
"Our scientists are working diligently to advance the treatment of Hepatitis C, which is a serious global epidemic that affects 170 million people worldwide," said John M. Leonard, M.D., senior vice president, Global Pharmaceutical Research and Development, Abbott. "As a global leader in the development of antiviral therapies, we are focused on building an industry-leading pipeline for the treatment of HCV and are well-positioned to explore multiple potent and new classes of HCV therapies that hold promise for patients."
While significant progress has been made in HCV treatment, there are limitations in efficacy and safety for the current standard of care. An extended duration of treatment (24 or 48 week course of a combination of pegylated alpha interferon and ribavirin) still results in a less-than 50% cure rate in those with HCV genotype 1. Additionally, the side-effects from interferon therapy can be highly problematic, often including depression and flu-like symptoms.
"Initiating Phase 2 is a key step in advancing our HCV collaboration," said Jay R. Luly, Ph.D., president and CEO of Enanta Pharmaceuticals. "We look forward to working with Abbott to advance our shared vision of creating breakthrough treatments for HCV infection."
The objectives of the Phase 2 study are to assess the safety, tolerability, pharmacokinetics, and antiviral activity of multiple dose strengths of ABT-450 or ABT-333 or ABT-072, each dosed individually in treatment-naïve adults infected with HCV genotype 1, the most common and difficult to treat form of the infection in the developed world. Initial antiviral activity will be evaluated via a 3-day monotherapy period. Subsequently, each antiviral agent will be administered with pegIFN/RBV (SOC) for 12-weeks, followed by treatment with SOC alone for an additional 36-weeks. Participants will then be monitored for sustained virologic response (SVR).
About Hepatitis C Virus
Hepatitis C is a liver disease affecting over 170 million people worldwide. The virus is spread through direct contact with the blood of an infected person. Hepatitis C increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death. Liver disease associated with HCV infection is growing rapidly, and current therapies only provide sustained benefit in about half of patients with the genotype 1 form of the virus. Specifically targeted antiviral therapies for HCV, such as NS3/4a protease inhibitors and non-nucleoside polymerase inhibitors, may have the potential to increase the proportion of patients in whom the virus can be eradicated.
About Enanta
Enanta Pharmaceuticals is a research and development company that uses its novel chemistry approach and drug discovery capabilities to create best in class small molecule drugs in the infectious disease field. Enanta is developing novel protease, NS5A, polymerase, and cyclophilin-based inhibitors targeted against the Hepatitis C virus (HCV). Additionally, the Company has created a new class of macrolide antibiotics, called Bicyclolides, which overcomes bacterial resistance. Antibacterial focus areas include superbugs, respiratory tract infections, and intravenous and oral treatments for hospital and community MRSA. Enanta is a privately held company headquartered in Watertown, MA. Enanta's news releases and other information are available on the company's web site at www.enanta.com.
About Abbott
Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs approximately 83,000 people and markets its products in more than 130 countries.
Abbott's news releases and other information are available on the company's web site at www.abbott.com.
SOURCE Abbott
Thursday, March 4, 2010
0abott and Enanta Launch Study of 3 Oral HCV Driugs in Phase 2
0abott and Enanta Launch Study of 3 Oral HCV Driugs in Phase 2
ABBOTT PARK, Ill. and WATERTOWN, Mass., March 2 /PRNewswire-FirstCall/
-- Abbott (NYSE: ABT) and Enanta Pharmaceuticals announced today the
advancement of their Hepatitis C (HCV) collaboration into Phase 2
clinical trials. The trial will evaluate three HCV antiviral agents,
including the investigational protease inhibitor ABT-450, part of the
Abbott-Enanta collaboration, and polymerase inhibitors ABT-333 and
ABT-072 currently being developed exclusively by Abbott. Each
antiviral agent will be dosed individually in combination with the
current standard of care (SOC).
ABT-450 was discovered as part of an alliance between Abbott and
Enanta. ABT-333 and ABT-072, both discovered internally at Abbott, are
part of the company's ongoing non-nucleoside polymerase inhibitor
development program.
"Our scientists are working diligently to advance the treatment of
Hepatitis C, which is a serious global epidemic that affects 170
million people worldwide," said John M. Leonard, M.D., senior vice
president, Global Pharmaceutical Research and Development, Abbott. "As a global leader in the development of antiviral therapies, we are
focused on building an industry-leading pipeline for the treatment of
HCV and are well-positioned to explore multiple potent and new classes qof HCV therapies that hold promise for patients."
While significant progress has been made in HCV treatment, there are
limitations in efficacy and safety for the current standard of care. An
extended duration of treatment (24 or 48 week course of a combination
of pegylated alpha interferon and ribavirin) still results in a
less-than 50% cure rate in those with HCV genotype 1. Additionally, the
side-effects from interferon therapy can be highly problematic, often
including depression and flu-like symptoms.
"Initiating Phase 2 is a key step in advancing our HCV collaboration,"
said Jay R. Luly, Ph.D., president and CEO of Enanta Pharmaceuticals.
"We look forward to working with Abbott to advance our shared vision of creating breakthrough treatments for HCV infection."
The objectives of the Phase 2 study are to assess the safety,
tolerability, pharmacokinetics, and antiviral activity of multiple dose
strengths of ABT-450 or ABT-333 or ABT-072, each dosed individually in
treatment-naïve adults infected with HCV genotype 1, the most common
and difficult to treat form of the infection in the developed world.
Initial antiviral activity will be evaluated via a 3-day monotherapy period. Subsequently, each antiviral agent will be administered with pegIFN/RBV (SOC) for 12-weeks, followed by treatment with SOC alone for
an additional 36-weeks. Participants will then be monitored for
sustained virologic response (SVR).
About Hepatitis C Virus
Hepatitis C is a liver disease affecting over 170 million people
worldwide. The virus is spread through direct contact with the blood
of an infected person. Hepatitis C increases a person's risk of
developing chronic liver disease, cirrhosis, liver cancer and death.
Liver disease associated with HCV infection is growing rapidly, and
current therapies only provide sustained benefit in about half of
patients with the genotype 1 form of the virus. Specifically targeted
antiviral therapies for HCV, such as NS3/4a protease inhibitors and
non-nucleoside polymerase inhibitors, may have the potential to
increase the proportion of patients in whom the virus can be eradicated.
About Enanta
Enanta Pharmaceuticals is a research and development company that uses
its novel chemistry approach and drug discovery capabilities to create
best in class small molecule drugs in the infectious disease field.
Enanta is developing novel protease, NS5A, polymerase, and
cyclophilin-based inhibitors targeted against the Hepatitis C virus
(HCV). Additionally, the Company has created a new class of macrolide
antibiotics, called Bicyclolides, which overcomes bacterial resistance.
Antibacterial focus areas include superbugs, respiratory tract
infections, and intravenous and oral treatments for hospital and
community MRSA. Enanta is a privately held company headquartered in
Watertown, MA. Enanta's news releases and other information are
available on the company's web site at www.enanta.com.
About Abbott
Abbott is a global, broad-based health care company devoted to the
discovery, development, manufacture and marketing of pharmaceuticals
and medical products, including nutritionals, devices and diagnostics.
The company employs approximately 83,000 people and markets its
products in more than 130 countries.
Abbott's news releases and other information are available on the
company's web site at www.abbott.com.
SOURCE Abbott
ABBOTT PARK, Ill. and WATERTOWN, Mass., March 2 /PRNewswire-FirstCall/
-- Abbott (NYSE: ABT) and Enanta Pharmaceuticals announced today the
advancement of their Hepatitis C (HCV) collaboration into Phase 2
clinical trials. The trial will evaluate three HCV antiviral agents,
including the investigational protease inhibitor ABT-450, part of the
Abbott-Enanta collaboration, and polymerase inhibitors ABT-333 and
ABT-072 currently being developed exclusively by Abbott. Each
antiviral agent will be dosed individually in combination with the
current standard of care (SOC).
ABT-450 was discovered as part of an alliance between Abbott and
Enanta. ABT-333 and ABT-072, both discovered internally at Abbott, are
part of the company's ongoing non-nucleoside polymerase inhibitor
development program.
"Our scientists are working diligently to advance the treatment of
Hepatitis C, which is a serious global epidemic that affects 170
million people worldwide," said John M. Leonard, M.D., senior vice
president, Global Pharmaceutical Research and Development, Abbott. "As a global leader in the development of antiviral therapies, we are
focused on building an industry-leading pipeline for the treatment of
HCV and are well-positioned to explore multiple potent and new classes qof HCV therapies that hold promise for patients."
While significant progress has been made in HCV treatment, there are
limitations in efficacy and safety for the current standard of care. An
extended duration of treatment (24 or 48 week course of a combination
of pegylated alpha interferon and ribavirin) still results in a
less-than 50% cure rate in those with HCV genotype 1. Additionally, the
side-effects from interferon therapy can be highly problematic, often
including depression and flu-like symptoms.
"Initiating Phase 2 is a key step in advancing our HCV collaboration,"
said Jay R. Luly, Ph.D., president and CEO of Enanta Pharmaceuticals.
"We look forward to working with Abbott to advance our shared vision of creating breakthrough treatments for HCV infection."
The objectives of the Phase 2 study are to assess the safety,
tolerability, pharmacokinetics, and antiviral activity of multiple dose
strengths of ABT-450 or ABT-333 or ABT-072, each dosed individually in
treatment-naïve adults infected with HCV genotype 1, the most common
and difficult to treat form of the infection in the developed world.
Initial antiviral activity will be evaluated via a 3-day monotherapy period. Subsequently, each antiviral agent will be administered with pegIFN/RBV (SOC) for 12-weeks, followed by treatment with SOC alone for
an additional 36-weeks. Participants will then be monitored for
sustained virologic response (SVR).
About Hepatitis C Virus
Hepatitis C is a liver disease affecting over 170 million people
worldwide. The virus is spread through direct contact with the blood
of an infected person. Hepatitis C increases a person's risk of
developing chronic liver disease, cirrhosis, liver cancer and death.
Liver disease associated with HCV infection is growing rapidly, and
current therapies only provide sustained benefit in about half of
patients with the genotype 1 form of the virus. Specifically targeted
antiviral therapies for HCV, such as NS3/4a protease inhibitors and
non-nucleoside polymerase inhibitors, may have the potential to
increase the proportion of patients in whom the virus can be eradicated.
About Enanta
Enanta Pharmaceuticals is a research and development company that uses
its novel chemistry approach and drug discovery capabilities to create
best in class small molecule drugs in the infectious disease field.
Enanta is developing novel protease, NS5A, polymerase, and
cyclophilin-based inhibitors targeted against the Hepatitis C virus
(HCV). Additionally, the Company has created a new class of macrolide
antibiotics, called Bicyclolides, which overcomes bacterial resistance.
Antibacterial focus areas include superbugs, respiratory tract
infections, and intravenous and oral treatments for hospital and
community MRSA. Enanta is a privately held company headquartered in
Watertown, MA. Enanta's news releases and other information are
available on the company's web site at www.enanta.com.
About Abbott
Abbott is a global, broad-based health care company devoted to the
discovery, development, manufacture and marketing of pharmaceuticals
and medical products, including nutritionals, devices and diagnostics.
The company employs approximately 83,000 people and markets its
products in more than 130 countries.
Abbott's news releases and other information are available on the
company's web site at www.abbott.com.
SOURCE Abbott
Vertex Broadens its Commitment to Improving HCV Care with Clinical Trial to Evaluate Combination Regimens Based on Oral Antiviral Therapies
Vertex Broadens its Commitment to Improving HCV Care with Clinical Trial to Evaluate Combination Regimens Based on Oral Antiviral Therapies
-Trial will evaluate safety and SVR rates with multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens of telaprevir and VX-222-
CAMBRIDGE, Mass., Mar 01, 2010 (BUSINESS WIRE) -- ---Interim clinical data expected in the second half of 2010-
---Multiple clinical trial sites in the U.S. to enroll patients-
Vertex Pharmaceuticals Incorporated (VRTX 41.43, +0.89, +2.20%) today announced that it is initiating the first clinical trial evaluating Vertex's lead investigational hepatitis C virus (HCV) protease inhibitor, telaprevir, dosed in combination with the company's lead investigational HCV polymerase inhibitor, VX-222. This Phase 2 trial will evaluate sustained viral response rates (SVR; defined as undetectable HCV RNA 24 weeks after the end of treatment) using multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens that contain only telaprevir and VX-222. The trial is expected to enroll approximately 100 treatment-naive genotype 1 HCV patients at multiple clinical trial sites, the majority of which will be located in the U.S. Enrollment is expected to be completed in the second quarter of 2010. Vertex expects to obtain interim clinical data, including safety and viral kinetic data, from this trial in the second half of 2010.
"Vertex is committed to improving patient care in HCV, and the announcement of this clinical trial combining two oral agents, telaprevir and VX-222, signifies our first exploration into this combination regimen's potential role to further improve the treatment of HCV," said Peter Mueller, Ph.D., Vertex's Chief Scientific Officer and Executive Vice President, Global Research and Development.
"The completion of the Phase 3 development program for telaprevir remains our primary focus, and we are on track to submit a New Drug Application for telaprevir in the second half of 2010. We believe telaprevir could represent a significant opportunity to improve the treatment of HCV, and simultaneously, we are focused on evaluating additional opportunities to potentially enhance HCV therapy even more in the years ahead using novel combination regimens based on oral antiviral agents. We believe the trial announced today will inform the development path for telaprevir/VX-222-based combination therapy, and we look forward to obtaining the first clinical data from the trial later this year," continued Dr. Mueller.
About the Phase 2 Trial of Telaprevir and VX-222
The randomized, parallel-group, dose-ranging trial announced today is designed to evaluate the safety and antiviral activity, including SVR, of multiple 12-week response-guided telaprevir/VX-222-based combination regimens. The primary endpoint of this trial is to assess safety and tolerability of telaprevir/VX-222-based combination therapy. A secondary endpoint of this study is to assess the proportion of patients in each study arm who achieve SVR. The trial is expected to enroll approximately 100 treatment-naive genotype 1 HCV patients at approximately 20 clinical trial sites, predominantly in the U.S. Vertex expects to complete enrollment for the trial in the second quarter of 2010. The trial will consist of four arms, as noted below:
12-Week Treatment Regimens Patient Enrollment
Telaprevir (1125 mg BID) + VX-222 (100 mg BID) 25
Telaprevir (1125 mg BID) + VX-222 (400 mg BID) 25
Telaprevir (1125 mg BID) + VX-222 (100 mg BID) + peg-IFN + RBV 25
Telaprevir (1125 mg BID) + VX-222 (400 mg BID) + peg-IFN + RBV 25
BID = twice daily, peg-IFN = pegylated interferon, RBV = ribavirin
Response-Guided Trial Design
The trial will utilize response-guided criteria aimed at evaluating shorter-duration treatment regimens. All patients, regardless of treatment group, whose HCV RNA levels are undetectable (<10 IU/mL) at week 2 and week 8 of treatment, will stop their assigned treatment at week 12. Patients who do not meet these criteria will complete their assigned treatment and at week 12, those in the dual-drug regimen will receive follow-on therapy of 24 weeks of pegylated-interferon (peg-IFN) and ribavirin (RBV), for a total of 36 weeks of treatment. Patients in the quad-therapy regimens who do not meet these criteria at week 12 will receive an additional 12 weeks of follow-on therapy with peg-IFN and RBV for a total of 24 weeks of peg-IFN and RBV therapy.
Potential Additional Arms of Telaprevir/VX-222-based Combination Treatment
Based on an evaluation of on-treatment safety, pharmacokinetic and antiviral data from patients in each arm of the trial, Vertex may elect to enroll up to two additional treatment arms that will evaluate telaprevir/VX-222-based combination therapy. The components of the treatment regimens of these arms will be selected based on clinical data that emerges from the four initially-studied regimens. If enacted, up to 25 patients are expected to enroll in each additional treatment arm.
Recent Clinical Trials Support Evaluation of Telaprevir/VX-222-based Combination Regimens
Phase 1b/2a Clinical Trial of VX-222 in HCV Patients
Interim clinical results from a two-part Phase 1b/2a clinical trial of VX-222 showed that in the multiple-dose Phase 1b viral kinetic portion of the trial (Part A), VX-222 was well-tolerated across four VX-222 dose groups with no serious adverse events reported. Part A enrolled 32 genotype 1 HCV patients to receive three days of dosing, and a mean HCV RNA decline of greater than 3 log10 was observed across all four VX-222 dose groups. An increasing dose response was observed across the four dose groups, with the results with 500 mg and 750 mg BID, and 1500 mg QD (once-daily) being very similar. The mean HCV RNA decline achieved after three days of dosing with 250 mg, 500 mg, and 750 mg of VX-222 every 12 hours (q12h) was 3.1 log10, 3.4 log10, and 3.2 log10, respectively. Additionally, the mean HCV RNA decline achieved after three days of dosing with 1500 mg of VX-222 every 24 hours (QD) was 3.4 log10. For patients who received placebo, the mean HCV RNA decline after three days of dosing was 0.1 log10. The majority of the patients enrolled in Part A had genotype 1a chronic HCV infection. Full results including the final safety analysis from Part A of this trial are expected to be presented at a medical meeting in 2010.
The interim results of Part A of this trial are consistent with the findings from a previously-conducted three-day, five-patient viral kinetic study of VX-222. Part B of the study, which will be initiated shortly will evaluate 12 weeks of VX-222 dosed in combination with peg-IFN and RBV in treatment-naive HCV patients.
Drug-Drug Interaction Study of Telaprevir and VX-222 in Healthy Volunteers
Vertex also recently completed a Phase 1 study of telaprevir and VX-222 designed to evaluate the safety, tolerability and drug-drug interaction of telaprevir and VX-222 in approximately 20 healthy volunteers. In the study, the 10-day telaprevir/VX-222-based combination regimens were well-tolerated with no serious adverse events reported.
In this study, an increase in the plasma exposure of VX-222 was observed when dosed in combination with telaprevir, while the plasma exposure of telaprevir was not affected when dosed in combination with VX-222. Based on this observation, Vertex selected VX-222 doses of 100 mg twice-daily BID and 400 mg BID for evaluation in the Phase 2 trial of telaprevir/VX-222-based combination therapy announced today. The VX-222 doses of 100 mg BID and 400 mg BID are expected to provide plasma exposures similar to those observed with doses of 250 mg BID and 750 mg BID, respectively, in the previously conducted viral kinetic studies of VX-222 monotherapy in HCV patients.
The results of both the three-day viral kinetic study of VX-222 and the drug-drug interaction study of telaprevir/VX-222-based regimens support the Phase 2 combination trial of telaprevir and VX-222 in HCV patients, as announced today.
About Telaprevir and VX-222
Telaprevir is an investigational oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being evaluated as part of a global Phase 3 registration program in more than 2,200 treatment-naive and treatment-failure patients. Vertex is collaborating with Tibotec and Mitsubishi Tanabe Pharma to develop telaprevir. Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and other countries. Mitsubishi has rights to commercialize telaprevir in Japan and certain Far East countries.
VX-222 is an investigational oral non-nucleoside inhibitor of HCV NS5B polymerase. Vertex added VX-222 to its development pipeline as part of the acquisition of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide commercial rights to VX-222.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is found in the blood of people with the disease. HCV, a serious public health concern affecting approximately 3.2 million individuals in the United States, is spread through direct contact with the blood of infected people.(1) Though many people with HCV infection may not experience symptoms, others may have symptoms such as jaundice, abdominal pain, fatigue and fever.(1) Chronic HCV significantly increases a person's risk for developing long-term infection, chronic liver disease, cirrhosis or death.(1)
Current therapies for HCV typically provide sustained benefit in about half of patients with genotype 1 HCV, the most common strain of the virus.(2) If treatment is not successful and patients do not achieve an SVR, they remain at risk for progressive liver disease.(1) In a recent study, the risk of liver failure, cancer or death following unsuccessful HCV treatment was assessed at 23% after 4 years, and 43% after 8 years.(3)
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer, and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva(R) is a registered trademark of the GlaxoSmithKline group of companies.
(1 )Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at:http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed, September 24, 2009.
(2) Strader DB, Wright T, Thomas DL, Seeff LB, AASLD practice guideline: diagnosis, management and treatment of hepatitis C. Hepatology: 2004(39):1147-1171.
(3 )Veldt et al, "Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis," Annals of Internal Medicine, 20 November 2007; 147: 677-684.
Special Note Regarding Forward Looking Statements
This press release contains forward-looking statements including (i) the expectation that the trial described in this press release will evaluate safety and SVR rates with multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens of telaprevir and VX-222 (ii) statements regarding the design of the trial, including the number of patients the Company expects to enroll, the primary endpoints, the expected treatment regimens, the response-guided design and the potential additional treatment arms; (iii) expectations regarding completing enrollment in the second quarter of 2010 and obtaining interim clinical data, including safety and viral kinetic data, from the trial in second half of 2010; (iv) Dr. Mueller's statements in paragraph 2 and 3 of this press release, including his statements regarding the telaprevir development program, the timing for submitting a New Drug Application for telaprevir and the trial announced today informing the future development path for telaprevir/VX-222-based combination therapy (v) statements regarding recent clinical trials supporting the evaluation of telaprevir/VX-222-based combination regimens and the expectations regarding the plasma exposures that are expected to be provided by the VX-222 doses selected for the clinical trial; and (vi) the expectation that Part B of the two part Phase 1b/2a trial of VX-222 will be initiated shortly. While the Company believes the forward-looking statements contained in this press release are accurate, those statements are subject to risks and uncertainties that could cause actual outcomes to vary materially from the outcomes referenced in the forward-looking statements. These risks and uncertainties include, among other things, the risks that efforts to develop telaprevir and VX-222 separately or in combination may not proceed due to technical, scientific, commercial, financial or other reasons, that clinical trials may not proceed as planned due to drug supply or patient enrollment issues, that additional clinical trials of telaprevir and VX-222 will not reflect the results obtained to date, that an adverse event profile for telaprevir or VX-222 could be revealed in further nonclinical or clinical studies that could put further development of telaprevir or VX-222 in jeopardy or adversely impact their therapeutic value, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
Vertex's press releases are available at www.vrtx.com.
(VRTX - GEN)
SOURCE: Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Media:
Zachry Barber, 617-444-6470
or
Amy Pasqua, 617- 444-6075
-Trial will evaluate safety and SVR rates with multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens of telaprevir and VX-222-
CAMBRIDGE, Mass., Mar 01, 2010 (BUSINESS WIRE) -- ---Interim clinical data expected in the second half of 2010-
---Multiple clinical trial sites in the U.S. to enroll patients-
Vertex Pharmaceuticals Incorporated (VRTX 41.43, +0.89, +2.20%) today announced that it is initiating the first clinical trial evaluating Vertex's lead investigational hepatitis C virus (HCV) protease inhibitor, telaprevir, dosed in combination with the company's lead investigational HCV polymerase inhibitor, VX-222. This Phase 2 trial will evaluate sustained viral response rates (SVR; defined as undetectable HCV RNA 24 weeks after the end of treatment) using multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens that contain only telaprevir and VX-222. The trial is expected to enroll approximately 100 treatment-naive genotype 1 HCV patients at multiple clinical trial sites, the majority of which will be located in the U.S. Enrollment is expected to be completed in the second quarter of 2010. Vertex expects to obtain interim clinical data, including safety and viral kinetic data, from this trial in the second half of 2010.
"Vertex is committed to improving patient care in HCV, and the announcement of this clinical trial combining two oral agents, telaprevir and VX-222, signifies our first exploration into this combination regimen's potential role to further improve the treatment of HCV," said Peter Mueller, Ph.D., Vertex's Chief Scientific Officer and Executive Vice President, Global Research and Development.
"The completion of the Phase 3 development program for telaprevir remains our primary focus, and we are on track to submit a New Drug Application for telaprevir in the second half of 2010. We believe telaprevir could represent a significant opportunity to improve the treatment of HCV, and simultaneously, we are focused on evaluating additional opportunities to potentially enhance HCV therapy even more in the years ahead using novel combination regimens based on oral antiviral agents. We believe the trial announced today will inform the development path for telaprevir/VX-222-based combination therapy, and we look forward to obtaining the first clinical data from the trial later this year," continued Dr. Mueller.
About the Phase 2 Trial of Telaprevir and VX-222
The randomized, parallel-group, dose-ranging trial announced today is designed to evaluate the safety and antiviral activity, including SVR, of multiple 12-week response-guided telaprevir/VX-222-based combination regimens. The primary endpoint of this trial is to assess safety and tolerability of telaprevir/VX-222-based combination therapy. A secondary endpoint of this study is to assess the proportion of patients in each study arm who achieve SVR. The trial is expected to enroll approximately 100 treatment-naive genotype 1 HCV patients at approximately 20 clinical trial sites, predominantly in the U.S. Vertex expects to complete enrollment for the trial in the second quarter of 2010. The trial will consist of four arms, as noted below:
12-Week Treatment Regimens Patient Enrollment
Telaprevir (1125 mg BID) + VX-222 (100 mg BID) 25
Telaprevir (1125 mg BID) + VX-222 (400 mg BID) 25
Telaprevir (1125 mg BID) + VX-222 (100 mg BID) + peg-IFN + RBV 25
Telaprevir (1125 mg BID) + VX-222 (400 mg BID) + peg-IFN + RBV 25
BID = twice daily, peg-IFN = pegylated interferon, RBV = ribavirin
Response-Guided Trial Design
The trial will utilize response-guided criteria aimed at evaluating shorter-duration treatment regimens. All patients, regardless of treatment group, whose HCV RNA levels are undetectable (<10 IU/mL) at week 2 and week 8 of treatment, will stop their assigned treatment at week 12. Patients who do not meet these criteria will complete their assigned treatment and at week 12, those in the dual-drug regimen will receive follow-on therapy of 24 weeks of pegylated-interferon (peg-IFN) and ribavirin (RBV), for a total of 36 weeks of treatment. Patients in the quad-therapy regimens who do not meet these criteria at week 12 will receive an additional 12 weeks of follow-on therapy with peg-IFN and RBV for a total of 24 weeks of peg-IFN and RBV therapy.
Potential Additional Arms of Telaprevir/VX-222-based Combination Treatment
Based on an evaluation of on-treatment safety, pharmacokinetic and antiviral data from patients in each arm of the trial, Vertex may elect to enroll up to two additional treatment arms that will evaluate telaprevir/VX-222-based combination therapy. The components of the treatment regimens of these arms will be selected based on clinical data that emerges from the four initially-studied regimens. If enacted, up to 25 patients are expected to enroll in each additional treatment arm.
Recent Clinical Trials Support Evaluation of Telaprevir/VX-222-based Combination Regimens
Phase 1b/2a Clinical Trial of VX-222 in HCV Patients
Interim clinical results from a two-part Phase 1b/2a clinical trial of VX-222 showed that in the multiple-dose Phase 1b viral kinetic portion of the trial (Part A), VX-222 was well-tolerated across four VX-222 dose groups with no serious adverse events reported. Part A enrolled 32 genotype 1 HCV patients to receive three days of dosing, and a mean HCV RNA decline of greater than 3 log10 was observed across all four VX-222 dose groups. An increasing dose response was observed across the four dose groups, with the results with 500 mg and 750 mg BID, and 1500 mg QD (once-daily) being very similar. The mean HCV RNA decline achieved after three days of dosing with 250 mg, 500 mg, and 750 mg of VX-222 every 12 hours (q12h) was 3.1 log10, 3.4 log10, and 3.2 log10, respectively. Additionally, the mean HCV RNA decline achieved after three days of dosing with 1500 mg of VX-222 every 24 hours (QD) was 3.4 log10. For patients who received placebo, the mean HCV RNA decline after three days of dosing was 0.1 log10. The majority of the patients enrolled in Part A had genotype 1a chronic HCV infection. Full results including the final safety analysis from Part A of this trial are expected to be presented at a medical meeting in 2010.
The interim results of Part A of this trial are consistent with the findings from a previously-conducted three-day, five-patient viral kinetic study of VX-222. Part B of the study, which will be initiated shortly will evaluate 12 weeks of VX-222 dosed in combination with peg-IFN and RBV in treatment-naive HCV patients.
Drug-Drug Interaction Study of Telaprevir and VX-222 in Healthy Volunteers
Vertex also recently completed a Phase 1 study of telaprevir and VX-222 designed to evaluate the safety, tolerability and drug-drug interaction of telaprevir and VX-222 in approximately 20 healthy volunteers. In the study, the 10-day telaprevir/VX-222-based combination regimens were well-tolerated with no serious adverse events reported.
In this study, an increase in the plasma exposure of VX-222 was observed when dosed in combination with telaprevir, while the plasma exposure of telaprevir was not affected when dosed in combination with VX-222. Based on this observation, Vertex selected VX-222 doses of 100 mg twice-daily BID and 400 mg BID for evaluation in the Phase 2 trial of telaprevir/VX-222-based combination therapy announced today. The VX-222 doses of 100 mg BID and 400 mg BID are expected to provide plasma exposures similar to those observed with doses of 250 mg BID and 750 mg BID, respectively, in the previously conducted viral kinetic studies of VX-222 monotherapy in HCV patients.
The results of both the three-day viral kinetic study of VX-222 and the drug-drug interaction study of telaprevir/VX-222-based regimens support the Phase 2 combination trial of telaprevir and VX-222 in HCV patients, as announced today.
About Telaprevir and VX-222
Telaprevir is an investigational oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being evaluated as part of a global Phase 3 registration program in more than 2,200 treatment-naive and treatment-failure patients. Vertex is collaborating with Tibotec and Mitsubishi Tanabe Pharma to develop telaprevir. Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and other countries. Mitsubishi has rights to commercialize telaprevir in Japan and certain Far East countries.
VX-222 is an investigational oral non-nucleoside inhibitor of HCV NS5B polymerase. Vertex added VX-222 to its development pipeline as part of the acquisition of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide commercial rights to VX-222.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is found in the blood of people with the disease. HCV, a serious public health concern affecting approximately 3.2 million individuals in the United States, is spread through direct contact with the blood of infected people.(1) Though many people with HCV infection may not experience symptoms, others may have symptoms such as jaundice, abdominal pain, fatigue and fever.(1) Chronic HCV significantly increases a person's risk for developing long-term infection, chronic liver disease, cirrhosis or death.(1)
Current therapies for HCV typically provide sustained benefit in about half of patients with genotype 1 HCV, the most common strain of the virus.(2) If treatment is not successful and patients do not achieve an SVR, they remain at risk for progressive liver disease.(1) In a recent study, the risk of liver failure, cancer or death following unsuccessful HCV treatment was assessed at 23% after 4 years, and 43% after 8 years.(3)
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer, and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva(R) is a registered trademark of the GlaxoSmithKline group of companies.
(1 )Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at:http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed, September 24, 2009.
(2) Strader DB, Wright T, Thomas DL, Seeff LB, AASLD practice guideline: diagnosis, management and treatment of hepatitis C. Hepatology: 2004(39):1147-1171.
(3 )Veldt et al, "Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis," Annals of Internal Medicine, 20 November 2007; 147: 677-684.
Special Note Regarding Forward Looking Statements
This press release contains forward-looking statements including (i) the expectation that the trial described in this press release will evaluate safety and SVR rates with multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens of telaprevir and VX-222 (ii) statements regarding the design of the trial, including the number of patients the Company expects to enroll, the primary endpoints, the expected treatment regimens, the response-guided design and the potential additional treatment arms; (iii) expectations regarding completing enrollment in the second quarter of 2010 and obtaining interim clinical data, including safety and viral kinetic data, from the trial in second half of 2010; (iv) Dr. Mueller's statements in paragraph 2 and 3 of this press release, including his statements regarding the telaprevir development program, the timing for submitting a New Drug Application for telaprevir and the trial announced today informing the future development path for telaprevir/VX-222-based combination therapy (v) statements regarding recent clinical trials supporting the evaluation of telaprevir/VX-222-based combination regimens and the expectations regarding the plasma exposures that are expected to be provided by the VX-222 doses selected for the clinical trial; and (vi) the expectation that Part B of the two part Phase 1b/2a trial of VX-222 will be initiated shortly. While the Company believes the forward-looking statements contained in this press release are accurate, those statements are subject to risks and uncertainties that could cause actual outcomes to vary materially from the outcomes referenced in the forward-looking statements. These risks and uncertainties include, among other things, the risks that efforts to develop telaprevir and VX-222 separately or in combination may not proceed due to technical, scientific, commercial, financial or other reasons, that clinical trials may not proceed as planned due to drug supply or patient enrollment issues, that additional clinical trials of telaprevir and VX-222 will not reflect the results obtained to date, that an adverse event profile for telaprevir or VX-222 could be revealed in further nonclinical or clinical studies that could put further development of telaprevir or VX-222 in jeopardy or adversely impact their therapeutic value, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
Vertex's press releases are available at www.vrtx.com.
(VRTX - GEN)
SOURCE: Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Investors:
Michael Partridge, 617-444-6108
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Risk of Non-AIDS Death in HIV/HCV-Coinfected People in SMART
Risk of Non-AIDS Death in HIV/HCV-Coinfected People in SMART
17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
- The SMART investigators proposed that, among people coinfected with HIV and a hepatitis virus, "those with impaired liver function are particularly in a pro-inflammatory state associated with excess risk of death from causes other than AIDS--and interruption of ART further exacerbates this pro-inflammatory state."
High levels of the liver fibrosis marker hyaluronic acid--coupled above-median readings of high-sensitivity C-reactive protein (hsCRP), IL-6, or D-dimer--raised the risk of non-AIDS death in HIV/(HCV/HBV)-coinfected SMART trial participants 4 to 6 times compared with people whose levels of these markers lay below the medians [1].
The role of inflammation markers (like IL-6 and hsCRP) and coagulation markers (like D-dimer) in the prognosis of HIV-infected people gained attention and credence when SMART researchers demonstrated that higher concentrations of these three markers upon entering SMART (a trial of continuous versus intermittent antiretroviral therapy) independently predicted a higher risk of death from any cause [2]. In this new analysis, SMART investigators probed for predictors of non-AIDS death by evaluating these markers and hyaluronic acid in SMART participants coinfected with HIV and HCV or HBV. They hypothesized that coinfected people with liver impairment signaled by high hyaluronic acid would also have high levels of the other markers and that the ability of biomarkers to predict non-AIDS death would depend on hyaluronic acid concentrations at study entry.
Among 5472 SMART enrollees, 655 (12%) had HCV or HBV infection, hyaluronic acid measured at entry, and samples available for other marker measurements. Most coinfected people had only HCV (82%), while 16% had only HBV and 2% carried both hepatitis viruses. Women accounted for 25% of the study group, which had a median age of 46 years (interquartile range [IQR] 40 to 50), a median CD4 count of 582 (IQR 461 to 737), and a median hyaluronic acid level of 30 ng/mL (IQR 17.5 to 57). But 122 people (18.6%) had hyaluronic acid concentrations above the upper normal range (75 ng/mL). Two thirds of this study group had an HIV load below 400 copies when the study began.
Fifty people died of non-AIDS causes through 6 months of follow-up, 30 in the intermittent-therapy arm and 20 in the continuous arm. There were 7 deaths from infection (14%), 6 from non-AIDS cancers (12%), 6 from substance abuse (12%), 4 from liver complications (8%), 4 form cardiovascular disease (8%), 4 from kidney disease (8%), 4 from violent death including suicide (8%), 1 each (2%) from chronic obstructive pulmonary disease and central nervous system disease, and 13 from unknown causes (26%).
Initial levels of IL-6, hsCRP, and D-dimer were all higher in people with a hyaluronic acid quotient above 75 ng/mL, but the difference was not statistically significantly for hsCRP. People randomized to intermittent antiretroviral therapy gained significantly more D-dimer, but not IL-6 or hsCRP, during follow-up. People in the intermittent arm with elevated baseline hyaluronic acid had a 47% increase in IL-6 through 6 months, while IL-6 dwindled 0.7% in intermittent-arm patients with normal hyaluronic acid.
SMART investigators divided people into four equal groups (quartiles) based on median baseline hyaluronic acid and marker levels. Subgroups with hyaluronic acid and hsCRP, IL-6, or D-dimer above the median at study entry accounted for 52%, 62%, and 48% of non-AIDS deaths. People with hyaluronic acid and each of the other markers below the medians accounted for only 8% of non-AIDS deaths.
To predict risk of non-AIDS death by marker combinations, the SMART team fashioned a model that considered SMART randomization, age, gender, race, prior AIDS, baseline CD4 count and viral load, nadir (lowest-ever) CD4 count, baseline antiretroviral status, alcohol abuse, and HBV status. Compared with paired hyaluronic acid-other biomarker levels below median values, paired levels above the medians independently raised the risk of non-AIDS death:
· High hyaluronic acid/hsCRP: hazard ratio [HR] 6.1, 95% confidence interval [CI] 2.1 to 17.7, P = 0.001
· High hyaluronic acid/IL-6: HR 5.9, 95% CI 2.0 to 17.3, P = 0.001
· High hyaluronic acid/D-dimer: HR 4.4, 95% CI 1.5 to 13.3, P = 0.008
The SMART investigators proposed that, among people coinfected with HIV and a hepatitis virus, "those with impaired liver function are particularly in a pro-inflammatory state associated with excess risk of death from causes other than AIDS--and interruption of ART further exacerbates this pro-inflammatory state."
References
1. Peters L for the INSIGHT SMART Study Group. Biomarkers of inflammation and coagulation and risk of non-AIDS death in HIV/hepatitis co-infected patients in the SMART study. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 660. http://www.retroconference.org/2010/PDFs/660.pdf.
2. Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5:e203. http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050203.
17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
- The SMART investigators proposed that, among people coinfected with HIV and a hepatitis virus, "those with impaired liver function are particularly in a pro-inflammatory state associated with excess risk of death from causes other than AIDS--and interruption of ART further exacerbates this pro-inflammatory state."
High levels of the liver fibrosis marker hyaluronic acid--coupled above-median readings of high-sensitivity C-reactive protein (hsCRP), IL-6, or D-dimer--raised the risk of non-AIDS death in HIV/(HCV/HBV)-coinfected SMART trial participants 4 to 6 times compared with people whose levels of these markers lay below the medians [1].
The role of inflammation markers (like IL-6 and hsCRP) and coagulation markers (like D-dimer) in the prognosis of HIV-infected people gained attention and credence when SMART researchers demonstrated that higher concentrations of these three markers upon entering SMART (a trial of continuous versus intermittent antiretroviral therapy) independently predicted a higher risk of death from any cause [2]. In this new analysis, SMART investigators probed for predictors of non-AIDS death by evaluating these markers and hyaluronic acid in SMART participants coinfected with HIV and HCV or HBV. They hypothesized that coinfected people with liver impairment signaled by high hyaluronic acid would also have high levels of the other markers and that the ability of biomarkers to predict non-AIDS death would depend on hyaluronic acid concentrations at study entry.
Among 5472 SMART enrollees, 655 (12%) had HCV or HBV infection, hyaluronic acid measured at entry, and samples available for other marker measurements. Most coinfected people had only HCV (82%), while 16% had only HBV and 2% carried both hepatitis viruses. Women accounted for 25% of the study group, which had a median age of 46 years (interquartile range [IQR] 40 to 50), a median CD4 count of 582 (IQR 461 to 737), and a median hyaluronic acid level of 30 ng/mL (IQR 17.5 to 57). But 122 people (18.6%) had hyaluronic acid concentrations above the upper normal range (75 ng/mL). Two thirds of this study group had an HIV load below 400 copies when the study began.
Fifty people died of non-AIDS causes through 6 months of follow-up, 30 in the intermittent-therapy arm and 20 in the continuous arm. There were 7 deaths from infection (14%), 6 from non-AIDS cancers (12%), 6 from substance abuse (12%), 4 from liver complications (8%), 4 form cardiovascular disease (8%), 4 from kidney disease (8%), 4 from violent death including suicide (8%), 1 each (2%) from chronic obstructive pulmonary disease and central nervous system disease, and 13 from unknown causes (26%).
Initial levels of IL-6, hsCRP, and D-dimer were all higher in people with a hyaluronic acid quotient above 75 ng/mL, but the difference was not statistically significantly for hsCRP. People randomized to intermittent antiretroviral therapy gained significantly more D-dimer, but not IL-6 or hsCRP, during follow-up. People in the intermittent arm with elevated baseline hyaluronic acid had a 47% increase in IL-6 through 6 months, while IL-6 dwindled 0.7% in intermittent-arm patients with normal hyaluronic acid.
SMART investigators divided people into four equal groups (quartiles) based on median baseline hyaluronic acid and marker levels. Subgroups with hyaluronic acid and hsCRP, IL-6, or D-dimer above the median at study entry accounted for 52%, 62%, and 48% of non-AIDS deaths. People with hyaluronic acid and each of the other markers below the medians accounted for only 8% of non-AIDS deaths.
To predict risk of non-AIDS death by marker combinations, the SMART team fashioned a model that considered SMART randomization, age, gender, race, prior AIDS, baseline CD4 count and viral load, nadir (lowest-ever) CD4 count, baseline antiretroviral status, alcohol abuse, and HBV status. Compared with paired hyaluronic acid-other biomarker levels below median values, paired levels above the medians independently raised the risk of non-AIDS death:
· High hyaluronic acid/hsCRP: hazard ratio [HR] 6.1, 95% confidence interval [CI] 2.1 to 17.7, P = 0.001
· High hyaluronic acid/IL-6: HR 5.9, 95% CI 2.0 to 17.3, P = 0.001
· High hyaluronic acid/D-dimer: HR 4.4, 95% CI 1.5 to 13.3, P = 0.008
The SMART investigators proposed that, among people coinfected with HIV and a hepatitis virus, "those with impaired liver function are particularly in a pro-inflammatory state associated with excess risk of death from causes other than AIDS--and interruption of ART further exacerbates this pro-inflammatory state."
References
1. Peters L for the INSIGHT SMART Study Group. Biomarkers of inflammation and coagulation and risk of non-AIDS death in HIV/hepatitis co-infected patients in the SMART study. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 660. http://www.retroconference.org/2010/PDFs/660.pdf.
2. Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5:e203. http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050203.
Anadys hepatitis C drug
Anadys hepatitis C drug
(AP) – 3 days ago
NEW YORK — Development-stage drug developer Anadys Pharmaceuticals Inc. said late Wednesday its developing hepatitis C drug was only slightly more effective at treating the virus than placebo in a midstage study.
The company's shares plunged 46 cents, or 20 percent, to $1.85 in premarket trading.
After 12 weeks, 73 percent of patients on the drug candidate ANA598 achieved undetectable levels of the virus, compared with 71 percent of patients on placebo. Meanwhile, the drug met safety goals in the study and was more effective than placebo in earlier time intervals.
The study involves 26 people. Smaller studies, such as early and midstage clinical trials, often focus more on safety than effectiveness. Often, there are too few people to determine effectiveness.
Oppenheimer analyst Dr. Brian Abrahams cut his investment rating on the company's shares to "Perform" from "Outperform" and removed his $8 price target on the stock. He said the more rapid effectiveness suggest that the drug candidate has some activity, but the 12-week data is concerning.
"The fact that '598's magnitude of benefit was not sufficient to overcome this anomalous placebo response is concerning (and unusual in HCV trials) and makes interpreting '598's contribution to efficacy challenging which could complicate partnership discussions," he said, in a note to investors Thursday.
The company has called the Phase II clinical study results preliminary.
Leerink Swann Research analyst Howard Liang reaffirmed his "Outperform" rating on the stock and said his key focus is on the study's safety results. Despite one case of severe rash, he said, there is no sign that indicates it is any worse than current treatments.
Meanwhile, Anadys Pharmaceuticals Inc. said its fourth-quarter loss narrowed on lower operating expenses.
The San Diego company lost $4.2 million, or 11 cents per share, compared with a loss of $8.5 million or 30 cents per share, during the same period a year prior. There was no revenue in either period. Operating expenses fell to $5.6 million from $8.9 million.
Analysts polled by Thomson Reuters expected a loss of 17 cents per share.
For the full year, the company lost $27.3 million, or 81 cents per share, compared with a loss of $32.4 million, or $1.13 per share, in 2008.
ANA598 Demonstrates 73% cEVR in Combination With Interferon and Ribavirin
No Viral Rebound Observed During 12 Weeks of ANA598 Dosing
Positive Safety Data with AE Profile Comparable to Control Group
Company to Review Data During Q4 Conference Call at 5:00 PM EST Today
SAN DIEGO, Feb. 24 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced preliminary results from an ongoing Phase II study demonstrating that 73% of hepatitis C patients treated with 200 mg ANA598 twice daily in combination with pegylated interferon and ribavirin (SOC) achieved undetectable levels of virus (<15 IU/mL) at week 12, known as complete Early Virological Response or cEVR.
No patient experienced viral rebound on ANA598. ANA598 was well tolerated through twelve weeks, with no serious adverse events reported and a profile of adverse events in the ANA598 group comparable to the group receiving SOC alone.
"The 73% cEVR demonstrated by ANA598 is comparable to the most advanced protease inhibitors currently in development for HCV," said Steve Worland, Ph.D., President and CEO of Anadys. "The durability of antiviral response through twelve weeks reflects ANA598's potency and long plasma half-life and suggests that resistance is unlikely to be a challenge to the use of ANA598 in appropriate combinations. Coupled with a very favorable safety profile to date, these results position ANA598 as an attractive candidate to advance in development, especially in combination with other direct antivirals."
Preliminary Antiviral Response Assessment
Picture 1.png
*At week 12, N=26 for the ANA598 group and 14 for the placebo group. One patient receiving ANA598 who had undetectable levels of virus at last measurement (week 4) and one patient receiving placebo who had a viral load of 150,000 IU/mL at last measurement (week 10) became unavailable and are excluded from weeks subsequent to their last measurement. The placebo values represent approximately half the overall placebo group, with the remainder of the placebo group being dosed presently, concurrently with patients receiving ANA598 400 mg bid.
ANA598 demonstrated comparable potency against genotypes 1a and 1b at twelve weeks, with cEVR rates of 74% and 71% respectively. No patient receiving ANA598 experienced viral rebound (defined as >1 log10 increase from a prior measurement) through week 12 and all patients who achieved undetectable levels of virus at any time during the 12 week period remained at undetectable levels at week 12.
Preliminary Safety Assessment
ANA598 at 200 mg given twice daily (bid) demonstrated a favorable safety and tolerability profile through 12 weeks, although conclusions regarding safety and tolerability cannot be made until additional results in more patients and potentially over longer duration are known. The incidence of all adverse events was similar between the active and placebo groups, with reported adverse events being typical for patients treated with interferon and ribavirin. There were no serious adverse events reported. The incidence of rash was comparable between groups and consistent with historical reports of rash rates due to interferon and ribavirin. In the ANA598 group 41% of patients (12/29) developed a rash while 33% (5/15) of patients in the placebo group developed a rash. Eleven of the twelve instances of rash in the ANA598 group were mild. One patient in the ANA598 group experienced a grade 3 rash which began resolving rapidly upon stopping all study medication. Per protocol, this patient resumed interferon/ribavirin alone and continued in the study. The five instances of rash in the placebo group were mild. 44 patients in the first cohort received at least one dose of study medications and are included in the safety database. Safety information for patients receiving placebo represents approximately half the overall placebo group, with the remainder of the placebo group being dosed presently, concurrently with patients receiving ANA598 400 mg bid.
Phase II Combination Study
In December 2009, Anadys reported positive initial antiviral response and safety results from the 200 mg bid dose cohort based on a planned interim analysis of data at four weeks. In the group receiving ANA598 added to SOC, there was a steady increase in the percentage of patients with undetectable levels of virus from week 1 through week 4, with 56% of patients achieving undetectable levels of virus at week 4 (defined as Rapid Virological Response or RVR), compared to 20% of patients receiving placebo plus SOC achieving an RVR. No patient receiving ANA598 experienced viral rebound (defined as >1 log10 increase from a prior measurement) through week 4. ANA598 also demonstrated a favorable safety profile through four weeks. There were no serious adverse events reported and the profile of adverse events reported was as expected for patients receiving SOC alone, with comparable rates observed between the ANA598 and placebo arms.
In the ongoing Phase II study, treatment-naive genotype 1 patients are to receive ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg or 400 mg both given twice daily (bid), each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieve undetectable levels of virus at weeks 4 and 12 will be randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients will be followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients are planned to be enrolled in this study – with approximately 30 patients receiving ANA598 and 15 receiving placebo at each dose level. The study is being managed by the Duke Clinical Research Institute (DCRI) under the leadership of John McHutchison, M.D. and is being conducted at a number of clinical sites in the United States.
About ANA598
ANA598 is a non-nucleoside inhibitor of the HCV RNA polymerase and is wholly owned by Anadys. Anadys has completed three Phase I clinical studies of ANA598 that have demonstrated potent antiviral activity and good tolerability. In a monotherapy study in treatment-naïve genotype 1 patients, treatment with ANA598 for three days led to median end-of-treatment declines in viral load ranging from 2.4 to 2.9 log10 in three separate dose groups. No patient at any dose level showed evidence of viral rebound while on ANA598, and there were no serious adverse events. Those patients from the monotherapy study who subsequently received pegylated interferon and ribavirin all exhibited further viral load decline, demonstrating that viral variants revealed by brief treatment with ANA598 remain susceptible to current SOC, consistent with prior in vitro results.
Anadys has completed two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). The No Observed Adverse Effect Level, or NOAEL, is 1000 mg/kg, the highest dose tested, in both the rat and monkey. The completed toxicology studies support the ongoing Phase II clinical study as well as future clinical studies of longer duration.
Anadys has presented in vitro data supporting the use of ANA598 in combination with interferon-alpha as well as with direct antivirals currently in development. In particular, data has shown that ANA598 is synergistic in vitro with interferon-alpha as well as representative HCV protease and polymerase inhibitors. In vitro combination treatment at clinically relevant concentrations of interferon-alpha and ANA598 results in clearance of HCV RNA from cells rather than selection of resistant isolates. Furthermore, ANA598 retains full activity in vitro against mutations conferring resistance to protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors that act at binding sites distinct from that of ANA598, while protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.
ANA598 has received Fast Track Status from the FDA for the treatment of chronic hepatitis C.
Conference Call Webcast and Slides
Anadys will hold a conference call and webcast today, Wednesday, February 24, 2010 at 5:00 p.m. Eastern Standard Time to discuss its fourth quarter and year end 2009 financial results and to discuss the 12 week safety and antiviral response data for the 200 mg bid cohort in the ongoing Phase II combination trial. A live webcast of the call, including accompanying slides, will be available online at www.anadyspharma.com. A telephone replay with slides will also be available approximately one hour after completion of the call. To access the telephone replay, dial 888-286-8010 (domestic) or 617-801-6888 (international), passcode 92658014. The webcast and telephone replay will be available through March 10, 2010.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) the belief that the durability of antiviral response through twelve weeks reflects ANA598's potency and long plasma half-life and suggests that resistance is unlikely to be a challenge to the use of ANA598 in appropriate combinations; (ii) assessments of the safety and tolerability profile of ANA598 based on the 200 mg bid 12 week results; (iii) future development activities with ANA598, including combination trials with other direct antivirals; and (iv) the ability for patients to achieve a SVR in the ANA598 study. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 will not have unforeseen safety issues or will continue to have favorable results as the Phase II trial progresses. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2008 and Anadys' Form 10-Q for the quarter ended September 30, 2009. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.
SOURCE Anadys Pharmaceuticals, Inc.
(AP) – 3 days ago
NEW YORK — Development-stage drug developer Anadys Pharmaceuticals Inc. said late Wednesday its developing hepatitis C drug was only slightly more effective at treating the virus than placebo in a midstage study.
The company's shares plunged 46 cents, or 20 percent, to $1.85 in premarket trading.
After 12 weeks, 73 percent of patients on the drug candidate ANA598 achieved undetectable levels of the virus, compared with 71 percent of patients on placebo. Meanwhile, the drug met safety goals in the study and was more effective than placebo in earlier time intervals.
The study involves 26 people. Smaller studies, such as early and midstage clinical trials, often focus more on safety than effectiveness. Often, there are too few people to determine effectiveness.
Oppenheimer analyst Dr. Brian Abrahams cut his investment rating on the company's shares to "Perform" from "Outperform" and removed his $8 price target on the stock. He said the more rapid effectiveness suggest that the drug candidate has some activity, but the 12-week data is concerning.
"The fact that '598's magnitude of benefit was not sufficient to overcome this anomalous placebo response is concerning (and unusual in HCV trials) and makes interpreting '598's contribution to efficacy challenging which could complicate partnership discussions," he said, in a note to investors Thursday.
The company has called the Phase II clinical study results preliminary.
Leerink Swann Research analyst Howard Liang reaffirmed his "Outperform" rating on the stock and said his key focus is on the study's safety results. Despite one case of severe rash, he said, there is no sign that indicates it is any worse than current treatments.
Meanwhile, Anadys Pharmaceuticals Inc. said its fourth-quarter loss narrowed on lower operating expenses.
The San Diego company lost $4.2 million, or 11 cents per share, compared with a loss of $8.5 million or 30 cents per share, during the same period a year prior. There was no revenue in either period. Operating expenses fell to $5.6 million from $8.9 million.
Analysts polled by Thomson Reuters expected a loss of 17 cents per share.
For the full year, the company lost $27.3 million, or 81 cents per share, compared with a loss of $32.4 million, or $1.13 per share, in 2008.
ANA598 Demonstrates 73% cEVR in Combination With Interferon and Ribavirin
No Viral Rebound Observed During 12 Weeks of ANA598 Dosing
Positive Safety Data with AE Profile Comparable to Control Group
Company to Review Data During Q4 Conference Call at 5:00 PM EST Today
SAN DIEGO, Feb. 24 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced preliminary results from an ongoing Phase II study demonstrating that 73% of hepatitis C patients treated with 200 mg ANA598 twice daily in combination with pegylated interferon and ribavirin (SOC) achieved undetectable levels of virus (<15 IU/mL) at week 12, known as complete Early Virological Response or cEVR.
No patient experienced viral rebound on ANA598. ANA598 was well tolerated through twelve weeks, with no serious adverse events reported and a profile of adverse events in the ANA598 group comparable to the group receiving SOC alone.
"The 73% cEVR demonstrated by ANA598 is comparable to the most advanced protease inhibitors currently in development for HCV," said Steve Worland, Ph.D., President and CEO of Anadys. "The durability of antiviral response through twelve weeks reflects ANA598's potency and long plasma half-life and suggests that resistance is unlikely to be a challenge to the use of ANA598 in appropriate combinations. Coupled with a very favorable safety profile to date, these results position ANA598 as an attractive candidate to advance in development, especially in combination with other direct antivirals."
Preliminary Antiviral Response Assessment
Picture 1.png
*At week 12, N=26 for the ANA598 group and 14 for the placebo group. One patient receiving ANA598 who had undetectable levels of virus at last measurement (week 4) and one patient receiving placebo who had a viral load of 150,000 IU/mL at last measurement (week 10) became unavailable and are excluded from weeks subsequent to their last measurement. The placebo values represent approximately half the overall placebo group, with the remainder of the placebo group being dosed presently, concurrently with patients receiving ANA598 400 mg bid.
ANA598 demonstrated comparable potency against genotypes 1a and 1b at twelve weeks, with cEVR rates of 74% and 71% respectively. No patient receiving ANA598 experienced viral rebound (defined as >1 log10 increase from a prior measurement) through week 12 and all patients who achieved undetectable levels of virus at any time during the 12 week period remained at undetectable levels at week 12.
Preliminary Safety Assessment
ANA598 at 200 mg given twice daily (bid) demonstrated a favorable safety and tolerability profile through 12 weeks, although conclusions regarding safety and tolerability cannot be made until additional results in more patients and potentially over longer duration are known. The incidence of all adverse events was similar between the active and placebo groups, with reported adverse events being typical for patients treated with interferon and ribavirin. There were no serious adverse events reported. The incidence of rash was comparable between groups and consistent with historical reports of rash rates due to interferon and ribavirin. In the ANA598 group 41% of patients (12/29) developed a rash while 33% (5/15) of patients in the placebo group developed a rash. Eleven of the twelve instances of rash in the ANA598 group were mild. One patient in the ANA598 group experienced a grade 3 rash which began resolving rapidly upon stopping all study medication. Per protocol, this patient resumed interferon/ribavirin alone and continued in the study. The five instances of rash in the placebo group were mild. 44 patients in the first cohort received at least one dose of study medications and are included in the safety database. Safety information for patients receiving placebo represents approximately half the overall placebo group, with the remainder of the placebo group being dosed presently, concurrently with patients receiving ANA598 400 mg bid.
Phase II Combination Study
In December 2009, Anadys reported positive initial antiviral response and safety results from the 200 mg bid dose cohort based on a planned interim analysis of data at four weeks. In the group receiving ANA598 added to SOC, there was a steady increase in the percentage of patients with undetectable levels of virus from week 1 through week 4, with 56% of patients achieving undetectable levels of virus at week 4 (defined as Rapid Virological Response or RVR), compared to 20% of patients receiving placebo plus SOC achieving an RVR. No patient receiving ANA598 experienced viral rebound (defined as >1 log10 increase from a prior measurement) through week 4. ANA598 also demonstrated a favorable safety profile through four weeks. There were no serious adverse events reported and the profile of adverse events reported was as expected for patients receiving SOC alone, with comparable rates observed between the ANA598 and placebo arms.
In the ongoing Phase II study, treatment-naive genotype 1 patients are to receive ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg or 400 mg both given twice daily (bid), each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieve undetectable levels of virus at weeks 4 and 12 will be randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients will be followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients are planned to be enrolled in this study – with approximately 30 patients receiving ANA598 and 15 receiving placebo at each dose level. The study is being managed by the Duke Clinical Research Institute (DCRI) under the leadership of John McHutchison, M.D. and is being conducted at a number of clinical sites in the United States.
About ANA598
ANA598 is a non-nucleoside inhibitor of the HCV RNA polymerase and is wholly owned by Anadys. Anadys has completed three Phase I clinical studies of ANA598 that have demonstrated potent antiviral activity and good tolerability. In a monotherapy study in treatment-naïve genotype 1 patients, treatment with ANA598 for three days led to median end-of-treatment declines in viral load ranging from 2.4 to 2.9 log10 in three separate dose groups. No patient at any dose level showed evidence of viral rebound while on ANA598, and there were no serious adverse events. Those patients from the monotherapy study who subsequently received pegylated interferon and ribavirin all exhibited further viral load decline, demonstrating that viral variants revealed by brief treatment with ANA598 remain susceptible to current SOC, consistent with prior in vitro results.
Anadys has completed two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). The No Observed Adverse Effect Level, or NOAEL, is 1000 mg/kg, the highest dose tested, in both the rat and monkey. The completed toxicology studies support the ongoing Phase II clinical study as well as future clinical studies of longer duration.
Anadys has presented in vitro data supporting the use of ANA598 in combination with interferon-alpha as well as with direct antivirals currently in development. In particular, data has shown that ANA598 is synergistic in vitro with interferon-alpha as well as representative HCV protease and polymerase inhibitors. In vitro combination treatment at clinically relevant concentrations of interferon-alpha and ANA598 results in clearance of HCV RNA from cells rather than selection of resistant isolates. Furthermore, ANA598 retains full activity in vitro against mutations conferring resistance to protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors that act at binding sites distinct from that of ANA598, while protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.
ANA598 has received Fast Track Status from the FDA for the treatment of chronic hepatitis C.
Conference Call Webcast and Slides
Anadys will hold a conference call and webcast today, Wednesday, February 24, 2010 at 5:00 p.m. Eastern Standard Time to discuss its fourth quarter and year end 2009 financial results and to discuss the 12 week safety and antiviral response data for the 200 mg bid cohort in the ongoing Phase II combination trial. A live webcast of the call, including accompanying slides, will be available online at www.anadyspharma.com. A telephone replay with slides will also be available approximately one hour after completion of the call. To access the telephone replay, dial 888-286-8010 (domestic) or 617-801-6888 (international), passcode 92658014. The webcast and telephone replay will be available through March 10, 2010.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) the belief that the durability of antiviral response through twelve weeks reflects ANA598's potency and long plasma half-life and suggests that resistance is unlikely to be a challenge to the use of ANA598 in appropriate combinations; (ii) assessments of the safety and tolerability profile of ANA598 based on the 200 mg bid 12 week results; (iii) future development activities with ANA598, including combination trials with other direct antivirals; and (iv) the ability for patients to achieve a SVR in the ANA598 study. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 will not have unforeseen safety issues or will continue to have favorable results as the Phase II trial progresses. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2008 and Anadys' Form 10-Q for the quarter ended September 30, 2009. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.
SOURCE Anadys Pharmaceuticals, Inc.
Avila Aims to Trump Vertex With Drug that Hits Hepatitis C Virus and Won’t Let Go
Avila Aims to Trump Vertex With Drug that Hits Hepatitis C Virus and Won’t Let Go
Luke Timmerman 2/26/10 http://www.xconomy.com
Avila Therapeutics can’t be accused of thinking too small. This Waltham, MA-based startup is on a quest to show it has the scientific chops to build a better drug than one of Boston’s anchor biotech companies—Vertex Pharmaceuticals.
So this is shaping up to be a big year for Avila (AH-vill-uh), as it plans to start clinical trials of a drug for hepatitis C, and another with potential for certain cancers and autoimmune diseases. The company raised $30 million last July, recruited an experienced biotech dealmaker as CEO, and has laid out some ambitious goals to put its money and people to work.
For those new to the Avila story, it’s built on chemistry. The company is developing conventional small-molecule oral pills with a special feature. The Avila drugs form covalent bonds with their targets on cells. These bonds are supposed to completely, and irreversibly, shut down the biological activity of the intended protein target they hit on cells. That’s different from conventional therapies that connect with their targets via ionic or van der Waal bonds, which puts them in a state of “dynamic equilibrium” in which they are bouncing on and off the target, says CEO Katrine Bosley.
Why does that matter? By completely shutting down the target, Avila thinks it has found a way to improve upon the trailblazing work of Vertex in hepatitis C, and it might be able to nail other targets pharma companies have long pursued, but couldn’t effectively block.
“It’s getting the attention of pharma companies. Pharma companies are always looking for new innovation from beyond what they do within their four walls, and covalent drugs haven’t been much explored in the industry,” Bosley says. “As we develop a data set that says we can develop very specific covalent drugs, it’s intrigued a lot of people. Scientists are scientists. If you can get a new result that can’t be achieved another way, they want to talk about that.”
Katrine Bosley
Katrine Bosley
I pressed Bosley for a bit more explanation of how its lead drug is differentiated from Vertex’s telaprevir. That drug, a protease inhibitor, has helped Vertex create an $8 billion stock market valuation, largely because clinical trials have shown it can basically double the traditional cure rates for patients with hepatitis C, while shortening the usual year-long treatment regimen by half. Analysts predict Vertex could exceed $2 billion in U.S. sales alone after a couple years on the market, and the worldwide potential is vast with an estimated 170 million people infected.
Bosley didn’t want to sound dismissive of what Vertex has done. “Obviously everybody is excited about Vertex’s telaprevir, it’s a great drug, they’ve done a beautiful job advancing the molecule and developing the clinical paradigm in treating hepatitis C,” Bosley says.
But Bosley clearly sees room for improvement, and Avila thinks it has found a way. One of the challenges with viruses is that they mutate, essentially switching
around an amino acid or two, which is a sort of a survival mechanism to escape from the pressure of a drug that’s trying to kill it, Bosley says. There are four or five slightly mutated versions of the hepatitis C protease, and the Vertex drug and others like it have varying degrees of potency when they encounter the mutants, she says.
The advantage of a covalent drug, which forms a permanent linkage with the target, is that it doesn’t allow the virus to escape via mutation, Bosley says. Plus, with hepatitis C, there are different genotypes of the virus to begin with. Vertex’s telaprevir is most effective against genotype 1, while Avila’s treatment is thought to be effective against all genotypes, she says.
“Telaprevir is a great drug, but if you want to improve upon it, you want to go across genotypes and across mutant forms. That’s the profile you want,” Bosley says.
So Avila went to work on making a covalent drug, AVL-181, to do that and more. It ought to completely shut down all the mutant forms of the hepatitis C virus, all genotypes, and, importantly, come in a convenient once-daily pill. Vertex has tested three-times daily dosing and twice-daily dosing of telaprevir in clinical trials, in its search for the best balance of safety, effectiveness, and convenience.
Avila didn’t generate nearly the same attention as clinical trial data from Vertex, but the startup had some data to support these remarks from animal experiments that was presented in November at the American Association for the Study of Liver Disease meeting in Boston. That was where the findings perked up the interest of partners, Bosley says.
The next program Avila has on the docket is a covalent binder against a target called Bruton’s tyrosine kinase (Btk). This target has been studied for years, but which has been an especially hard target for medicinal chemists to hit in the pharmaceutical industry. It’s thought to be valuable because it’s involved in activating immune system B-cells, which can flip into overdrive, harming healthy tissues, and leading to certain lymphomas or autoimmune diseases like rheumatoid arthritis and multiple sclerosis, Bosley says.
The role of B-cell proliferation in those cancers and autoimmune diseases has been proven over the years by rituximab (Rituxan), the hit antibody drug from Roche and Biogen that depletes excess B-cells.
Avila presented a poster at the American Association for Cancer Research meeting last spring, in which it suggested it had developed a potent covalent-binding drug against this notorious hard target. It’s a conventional small-molecule that can be taken orally once a day. The research is still at an early stage, not yet in the clinic, but this also turned some heads.
“A lot of people find you from the scientific data you put out there. People are quite intrigued on a couple fronts. People have known about the Btk target for a long time. They like the target, and a lot of people have worked on it and not achieved the profile they’d like. So when they see a poster, they say ‘Oh, you have a potent and specific Btk inhibitor? Let’s talk.’”
Talk is great, but clinical data and partnership deals speak volumes in biotech. Bosley has experience doing deals, as a former vice president of business development at Biogen, and a vice-president of Adnexus Therapeutics before that company was bought by Bristol-Myers Squibb. If Bosley and the Avila team can deliver on some of this early promise, it will be one of the young biotech startups to watch in Boston this year.
Luke Timmerman is the National Biotechnology Editor for Xconomy
Luke Timmerman 2/26/10 http://www.xconomy.com
Avila Therapeutics can’t be accused of thinking too small. This Waltham, MA-based startup is on a quest to show it has the scientific chops to build a better drug than one of Boston’s anchor biotech companies—Vertex Pharmaceuticals.
So this is shaping up to be a big year for Avila (AH-vill-uh), as it plans to start clinical trials of a drug for hepatitis C, and another with potential for certain cancers and autoimmune diseases. The company raised $30 million last July, recruited an experienced biotech dealmaker as CEO, and has laid out some ambitious goals to put its money and people to work.
For those new to the Avila story, it’s built on chemistry. The company is developing conventional small-molecule oral pills with a special feature. The Avila drugs form covalent bonds with their targets on cells. These bonds are supposed to completely, and irreversibly, shut down the biological activity of the intended protein target they hit on cells. That’s different from conventional therapies that connect with their targets via ionic or van der Waal bonds, which puts them in a state of “dynamic equilibrium” in which they are bouncing on and off the target, says CEO Katrine Bosley.
Why does that matter? By completely shutting down the target, Avila thinks it has found a way to improve upon the trailblazing work of Vertex in hepatitis C, and it might be able to nail other targets pharma companies have long pursued, but couldn’t effectively block.
“It’s getting the attention of pharma companies. Pharma companies are always looking for new innovation from beyond what they do within their four walls, and covalent drugs haven’t been much explored in the industry,” Bosley says. “As we develop a data set that says we can develop very specific covalent drugs, it’s intrigued a lot of people. Scientists are scientists. If you can get a new result that can’t be achieved another way, they want to talk about that.”
Katrine Bosley
Katrine Bosley
I pressed Bosley for a bit more explanation of how its lead drug is differentiated from Vertex’s telaprevir. That drug, a protease inhibitor, has helped Vertex create an $8 billion stock market valuation, largely because clinical trials have shown it can basically double the traditional cure rates for patients with hepatitis C, while shortening the usual year-long treatment regimen by half. Analysts predict Vertex could exceed $2 billion in U.S. sales alone after a couple years on the market, and the worldwide potential is vast with an estimated 170 million people infected.
Bosley didn’t want to sound dismissive of what Vertex has done. “Obviously everybody is excited about Vertex’s telaprevir, it’s a great drug, they’ve done a beautiful job advancing the molecule and developing the clinical paradigm in treating hepatitis C,” Bosley says.
But Bosley clearly sees room for improvement, and Avila thinks it has found a way. One of the challenges with viruses is that they mutate, essentially switching
around an amino acid or two, which is a sort of a survival mechanism to escape from the pressure of a drug that’s trying to kill it, Bosley says. There are four or five slightly mutated versions of the hepatitis C protease, and the Vertex drug and others like it have varying degrees of potency when they encounter the mutants, she says.
The advantage of a covalent drug, which forms a permanent linkage with the target, is that it doesn’t allow the virus to escape via mutation, Bosley says. Plus, with hepatitis C, there are different genotypes of the virus to begin with. Vertex’s telaprevir is most effective against genotype 1, while Avila’s treatment is thought to be effective against all genotypes, she says.
“Telaprevir is a great drug, but if you want to improve upon it, you want to go across genotypes and across mutant forms. That’s the profile you want,” Bosley says.
So Avila went to work on making a covalent drug, AVL-181, to do that and more. It ought to completely shut down all the mutant forms of the hepatitis C virus, all genotypes, and, importantly, come in a convenient once-daily pill. Vertex has tested three-times daily dosing and twice-daily dosing of telaprevir in clinical trials, in its search for the best balance of safety, effectiveness, and convenience.
Avila didn’t generate nearly the same attention as clinical trial data from Vertex, but the startup had some data to support these remarks from animal experiments that was presented in November at the American Association for the Study of Liver Disease meeting in Boston. That was where the findings perked up the interest of partners, Bosley says.
The next program Avila has on the docket is a covalent binder against a target called Bruton’s tyrosine kinase (Btk). This target has been studied for years, but which has been an especially hard target for medicinal chemists to hit in the pharmaceutical industry. It’s thought to be valuable because it’s involved in activating immune system B-cells, which can flip into overdrive, harming healthy tissues, and leading to certain lymphomas or autoimmune diseases like rheumatoid arthritis and multiple sclerosis, Bosley says.
The role of B-cell proliferation in those cancers and autoimmune diseases has been proven over the years by rituximab (Rituxan), the hit antibody drug from Roche and Biogen that depletes excess B-cells.
Avila presented a poster at the American Association for Cancer Research meeting last spring, in which it suggested it had developed a potent covalent-binding drug against this notorious hard target. It’s a conventional small-molecule that can be taken orally once a day. The research is still at an early stage, not yet in the clinic, but this also turned some heads.
“A lot of people find you from the scientific data you put out there. People are quite intrigued on a couple fronts. People have known about the Btk target for a long time. They like the target, and a lot of people have worked on it and not achieved the profile they’d like. So when they see a poster, they say ‘Oh, you have a potent and specific Btk inhibitor? Let’s talk.’”
Talk is great, but clinical data and partnership deals speak volumes in biotech. Bosley has experience doing deals, as a former vice president of business development at Biogen, and a vice-president of Adnexus Therapeutics before that company was bought by Bristol-Myers Squibb. If Bosley and the Avila team can deliver on some of this early promise, it will be one of the young biotech startups to watch in Boston this year.
Luke Timmerman is the National Biotechnology Editor for Xconomy
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