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Estimating future hepatitis C morbidity, mortality, and costs in the United States
This study estimated future morbidity, mortality, and costs resulting from hepatitis C virus (HCV). We used a computer cohort simulation of the natural history of HCV in the US population.
From the year 2010 through 2019, our model projected 165,900 deaths from chronic liver disease, 27,200 deaths from hepatocellular carcinoma, and $10.7 billion in direct medical expenditures for HCV. During this period, HCV may lead to 720,700 years of decompensated cirrhosis and hepatocellular carcinoma and to the loss of 1.83 million years of life in those younger than 65 at a societal cost of $21.3 and $54.2 billion, respectively. In sensitivity analysis, these estimates depended on (1) whether patients with HCV and normal transaminase levels develop progressive liver disease, (2) the extent of alcohol ingestion, and (3) the likelihood of dying from other causes related to the route of HCV acquisition.
Our projections for hepatitis C likely underestimated the long-term costs be-cause they did not include future expenses related to periodic liver biopsy, screening for hepatocellular carcinoma, and treatment costs. Moreover, our estimates applied variable costs (the additional cost to treat 1 more patient) and not charges (retail price) or total costs (including fixed costs or overhead). The latter are typically 2 to 3 times higher. For example, in this analysis, liver transplantation cost $108,659 for the first year and $18, 976 per year subsequently (in 1999 dollars), but other studies that used charge data reported transplantation costs of $200,000 or higher for the surgery and $25,000 per year for medications.
Our estimates did not consider the possibility of accelerated HCV progression in older individuals or those co-infected with hepatitis B or HIV, who are more likely to develop hepatic complications.
Based on the 2 million individuals who had detectable viral RNA for HCV and who presumably had elevated liver transaminases in 1991, our model predicted that annual HCV-related liver deaths for the years 2010 to 2019 would increase 2-fold when compared with the 8000 deaths in 1991. HCV-related chronic liver disease mortality would be 181,300 over this 10-year period, with another 27,200 deaths from HCV-related hepatocellular carcinoma. The highest proportion of deaths related to hepatitis C would occur 10 to 20 years from now, peaking in 2014. The need for liver transplants would rise until 2015. Because of the higher risk for decompensated liver disease and the relatively low risk of cancer assumed for this analysis, new cases of hepatocellular carcinoma would rise only until 2008 but would remain relatively stable throughout the next 20 years, varying by at most several hundred. Figure 3 shows the estimated annual direct medical care costs. For the 10-year period from 2010 to 2019, direct medical expenditures would be $10.7 billion.
Our results confirm prior Centers for Disease Control and Prevention projections and suggest that HCV may lead to a substantial health and economic burden over the next 10 to 20 years.
Our results suggested that despite the remarkable decline in the incidence of hepatitis C, mortality related to existing cases of hepatitis C in 1991 will likely continue to increase over the next 10 to 20 years, and our results confirmed that hepatitis C may be an awakening giant. Although screening tests and treatments are available, waiting times for new patient appointments to see a hepatologist for evaluation of hepatitis C in some parts of the United States have increased to several months, emphasizing the need to train clinicians in the management of hepatitis C. There is some urgency for action because hepatitis C is frequently asymptomatic until cirrhosis develops, at which time treatment is less effective. Once hepatic decompensation occurs, treatment is limited by the shortage of donor transplant organs. Additional research regarding the cost-effectiveness of screening for hepatitis C and indications for treatment should be pursued to help formu-late public health policy in this area. Continued research on the natural history of he-patitis C and the development of new treatments should remain priorities for the nationÕs health.
American Journal of Public Health, Vol 90, Issue 10 1562-1569
JB Wong, GM McQuillan, JG McHutchison and T Poynard
Department of Medicine, New England Medical Center, Tupper Research Institute,
Tufts University School of Medicine, Boston, Mass., USA.
EFFECT OF TREATMENT MANAGEMENT ALGORITHMS ON RIBAVIRIN AND PEGINTERFERON ALFA-2B COSTS FOR CHRONIC HEPATITIS C
AASLD, Nov 2002
Peginterferon alfa-2b and ribavirin have the highest sustained response rates for chronic hepatitis C but published drug cost estimates usually assume full dosing for 48 weeks. These estimates neglect dose reductions and discontinuations that occur during treatment as well as clinical management algorithms that lead to drug stoppage in those unlikely to benefit from further therapy.
The aim of this study is to estimate the antiviral drug costs associated with peginterferon alfa-2b+ribavirin. We analyzed actual drug dosing for 511 patients who were intended to receive 800 mg of ribavirin daily and 1.5 mcg/kg peginterferon alfa-2b weekly (PegR8) for 48 weeks and for the subset receiving >10.6 mg/kg of ribavirin (PegRW) (Manns Lancet). Based on ribavirin capsules and peginterferon vials used in this trial, we determined the drug costs for 1) full dosing (Full), 2) intent to treat with reductions and discontinuations as occurred in the trial (ITT), 3) discontinuing therapy in those who were HCV RNA-positive after 24 weeks (Stop24), 4) criteria in Stop24 and also limiting therapy in those with genotype 2/3 to 24 weeks (Stop2/3), and 5) criteria in Stop2/3 and also discontinuing therapy in those viral positive or with <2 log drop in viral load in non-genotype 2/3 patients after 12 weeks (Stop12). Any missing PCR values were assumed to be positive.
The table shows the drug costs for both regimens and shows that these management algorithms result in substantial reductions in likely drug costs. Checking a qualitative PCR at week 24 would allow discontinuation in the 31-36% of patients who are unlikely to respond with further therapy. If the duration of therapy is also limited to 24 weeks for those with genotype 2/3, in all, 60-61% may stop therapy after 24 weeks. Checking a qualitative and a quantitative PCR at week 12 and discontinuing therapy for those PCR positive with <2 log decrease in viral load would allow stopping therapy for 23-24% of patients at week12. Because most genotype 2/3 patients respond by 12 weeks, also applying the same Stop12 rule for those with genotype 2/3 would only increase drug stoppage at week 12 to 24-26% of all patients. Although the goal was 48 weeks of treatment, the overall observed ITT mean duration of therapy was 42 weeks. Alternative management algorithms would decrease the overall mean duration of therapy for all patients to 37 weeks with Stop24, 31 weeks with Stop2/3 and 29 weeks with Stop12. For the 61-62% of patients affected by these treatment management algorithms, the observed mean 40 week therapy duration with ITT would be reduced to 31-32 weeks with Stop24, 21 weeks with Stop2/3 and 18-19 weeks with Stop12.
Our results suggest that treatment management algorithms substantially reduce antiviral drug costs and the duration of therapy. Drug costs should be weighed against the cost and likelihood of complications from hepatitis C and should consider therapeutic effectiveness. Individual decisions to continue ribavirin and peginterferon alfa-2b should also consider the potential clinical benefits for specific patient characteristics, such as advanced fibrosis.
John B Wong, Tufts-New England Medical Center, Boston, MA; Gary L Davis, Baylor University Medical Center, Dallas, TX; John G McHutchison, Scripps Clinic, La Jolla, CA; Michael P Manns, Medizinische Hochschule Hannover, Hannover, Germany; Janice K Albrecht, Schering-Plough Research Institute, Kenilworth, NJ
Tuesday, July 7, 2009
Oral Interferon-Alpha Lozenges Study
Oral Interferon-Alpha Lozenges Study - Amarillo, CytoPharm Intiates Enrollment For Hepatitis-C Study
Published:29-June-2009
By Staff Reporter
http://www.pharmaceutical-business-review.com
Amarillo (ABI) and CytoPharm have started the enrollment for a study of ABI's oral interferon-alpha lozenges, for chronic hepatitis-C virus infection.
The aim of the trial is to reduce the virologic relapse rate for patients who have completed the standard combination therapy, which consists of high dose injectable interferon-alpha and Ribavirin. Although most patients respond to the standard therapy, up to 50% of those with certain high-risk viral genotypes relapse after treatment.
In this study, a total of 165 patients who test positive for a high-risk hepatitis C viral genotype, will receive one of two different doses of human interferon-alpha or placebo given daily for 24 weeks. Full study enrollment is expected to complete by the end of the year.
The companies announced that CytoPharm is planning a study of oral interferon lozenges in the treatment of influenza, which is to be launched during the 2009/2010 flu season in Taiwan.
Published:29-June-2009
By Staff Reporter
http://www.pharmaceutical-business-review.com
Amarillo (ABI) and CytoPharm have started the enrollment for a study of ABI's oral interferon-alpha lozenges, for chronic hepatitis-C virus infection.
The aim of the trial is to reduce the virologic relapse rate for patients who have completed the standard combination therapy, which consists of high dose injectable interferon-alpha and Ribavirin. Although most patients respond to the standard therapy, up to 50% of those with certain high-risk viral genotypes relapse after treatment.
In this study, a total of 165 patients who test positive for a high-risk hepatitis C viral genotype, will receive one of two different doses of human interferon-alpha or placebo given daily for 24 weeks. Full study enrollment is expected to complete by the end of the year.
The companies announced that CytoPharm is planning a study of oral interferon lozenges in the treatment of influenza, which is to be launched during the 2009/2010 flu season in Taiwan.
Abbott HCV NNRTI polymerase inhibitor ABT-333
New HCV Drugs, Special Population (Coinfectio) Access: 4th International Workshop on Hepatitis C, Resistance and New Compounds 25-26 June 2009, Boston, MA U
Reported by Jules Levin
June 25-26 2009, Boston, Mass
I am in Boston at the 4th Intl Workshop on Hepatitis C - Resistance & New Compounds June 25-26 2009 followed on saturday by the HCV Clinical Pharmacology one-day meeting, by the Charles Boucher group. Saturday is the HCV Clinical Pharmacology Meeting at the same venue and a report by NATAP is forthcoming.
Friday June 26
D Cohen from Abbott just presented data for the first time publicly on the Abbott HCV NNRTI polymerase inhibitor ABT-333 on 2 day monotherapy at increasing doses in naives in genotype 1 in patients at the HCV meeting in Boston now. Doses ranged from 100 mg once and twice daily and also 600 mg once & twice daily. 2/3 of patients has genotype 1a. They reported no treatment related adverse events. With the 600 mg bid maximal mean change was -1.52 logs, 2 patients achieved -2.09 to -2.21 log reduction. One patient had -1.27 and another -0.75 log after 2 days. The study was not intended to characterize maximal viral load response and this will be assessed in further combination studies. Safety was good, one patient developed elevated ALT after stopping therapy and phase 2a study is ongoing. Abbott also is developing HCV protease inhibitors.
At the HCV meeting in Boston ongoing today there was a talk by someone from the FDA when I took the opportunity to speak about the need for early access for 2 oral HCV drugs in combination with pegIFN and RBV for patients who are coinfected due to the risk for accelerated disease and for patients with advanced HCV disease. Both of these patient populations likely have genotype 1 or are nonresponders and need early access to a regimen with a better chance for achieving SVR. This would be for patients who cannot wait, who make a decision with their doctor that they cannot risk deferring therapy. This would be for patients who are at greater risk for decompensation and death. One HCV protease inhibitor plus peg/RBV may not be adequate therapy and put the patient at risk but 2 orals plus peg/RBV provides a much better chance for success.
Thursday June 25
The first presentation today was by a research group at the Cleveland Clinic that RNase L is a host target for anti-HCV drug development.
The 2nd talk is about a new HCV drug AVL-181. "Using a new paradigm in the design of inhibitors of hepatitis C virus protease, we have designed a novel compound with the ability to rapidly and completely silence HCv protease through covalent bonding of the protein. AVL-181 is a potent inhibitor of wild-type and drug resistant HCV protease mutations with pharmacokinetic and pharmacodynamic properties to enable once daily dosing. M Hagel from Avila Therapeutics said this drug in vitro is twice as potent as telaprevir. AVL-181 is the first experimental agent in a new paradigm for the treatment of HCV that has the potential to overcome the clinical liabilities of current investigational HCV-P inhibitors. AVL-181 has a rapid onset of inhibition (< 1 hr) in a direct in vitro assay of HCV-P activity against wild-type and drug-resistant mutations and this activity is prolonged for greater than 24 hours after compound removal, a property not observed with current HCV protease inhibitors." I think they said it could be active across genotypes. AVL-181 inhibitis some HCV protease mutaions such as the R155K mutation associated with other protease inhibitors currently in studies in patients. The drug is a potent inhibitor of wild-type HCV-P in biochemical (IC50=0.4nM) and replicon cellular (EC50=4.6nM) in vitro assays. The drug works in a unique way and suggests efficacy against HCV protease inhibitors. The resistance profile of the drug is being studied and they said it would be presented at AASLD.
The 3rd talk this morning is by G Wang from Enanta who is developing HCV protease inhibitors along with Abbott. They have a series of compounds but EA-383 appears to be a lead compound. EA-383 appears potent in vitro and is active against all genotypes but a little better against genotype 1. The drug has a "very" high exposure in the liver and a high liver-plasma concentration and a 600 times higher concentration in the liver than in the plasma, even 24 hours after dosing had a high liver level. He said it is potent against HCV resistant mutants which will be presented next by Krishnan from Abbott.
Preethi Krishnan from Abbott is now presenting on this series of protease inhibitors. These are different types of HCV protease inhibitors than others in development. EA-383 has a higher genetic barrier than other compounds to resistance to the usual mutations. In vitro ES-383 showed about a 4.5 log viral log reduction. In vitro they showed data that EA-383 was more potent than ITMN-191 in genotype 1. It appears more potent in vitro against geno 1A. the data presented reported EA-383 was active against some HCV protease mutations but not other mutations. So I asked the presenter about that - if a patient fails a protease inhibitor with several protease mutations EA-383 did not appear to be able to suppress such a virus. In response Krishnan said if they could reach high blood levels with this drug perhaps they could suppress resistant viruses, and if a patient fails with only the mutation against which EA-383 is active then EA-383 could be potently active. Then Dale Kempf spoke and I think he suggested the 155 and 168, the usual HCV PI mutations could be problematic.
Reported by Jules Levin
June 25-26 2009, Boston, Mass
I am in Boston at the 4th Intl Workshop on Hepatitis C - Resistance & New Compounds June 25-26 2009 followed on saturday by the HCV Clinical Pharmacology one-day meeting, by the Charles Boucher group. Saturday is the HCV Clinical Pharmacology Meeting at the same venue and a report by NATAP is forthcoming.
Friday June 26
D Cohen from Abbott just presented data for the first time publicly on the Abbott HCV NNRTI polymerase inhibitor ABT-333 on 2 day monotherapy at increasing doses in naives in genotype 1 in patients at the HCV meeting in Boston now. Doses ranged from 100 mg once and twice daily and also 600 mg once & twice daily. 2/3 of patients has genotype 1a. They reported no treatment related adverse events. With the 600 mg bid maximal mean change was -1.52 logs, 2 patients achieved -2.09 to -2.21 log reduction. One patient had -1.27 and another -0.75 log after 2 days. The study was not intended to characterize maximal viral load response and this will be assessed in further combination studies. Safety was good, one patient developed elevated ALT after stopping therapy and phase 2a study is ongoing. Abbott also is developing HCV protease inhibitors.
At the HCV meeting in Boston ongoing today there was a talk by someone from the FDA when I took the opportunity to speak about the need for early access for 2 oral HCV drugs in combination with pegIFN and RBV for patients who are coinfected due to the risk for accelerated disease and for patients with advanced HCV disease. Both of these patient populations likely have genotype 1 or are nonresponders and need early access to a regimen with a better chance for achieving SVR. This would be for patients who cannot wait, who make a decision with their doctor that they cannot risk deferring therapy. This would be for patients who are at greater risk for decompensation and death. One HCV protease inhibitor plus peg/RBV may not be adequate therapy and put the patient at risk but 2 orals plus peg/RBV provides a much better chance for success.
Thursday June 25
The first presentation today was by a research group at the Cleveland Clinic that RNase L is a host target for anti-HCV drug development.
The 2nd talk is about a new HCV drug AVL-181. "Using a new paradigm in the design of inhibitors of hepatitis C virus protease, we have designed a novel compound with the ability to rapidly and completely silence HCv protease through covalent bonding of the protein. AVL-181 is a potent inhibitor of wild-type and drug resistant HCV protease mutations with pharmacokinetic and pharmacodynamic properties to enable once daily dosing. M Hagel from Avila Therapeutics said this drug in vitro is twice as potent as telaprevir. AVL-181 is the first experimental agent in a new paradigm for the treatment of HCV that has the potential to overcome the clinical liabilities of current investigational HCV-P inhibitors. AVL-181 has a rapid onset of inhibition (< 1 hr) in a direct in vitro assay of HCV-P activity against wild-type and drug-resistant mutations and this activity is prolonged for greater than 24 hours after compound removal, a property not observed with current HCV protease inhibitors." I think they said it could be active across genotypes. AVL-181 inhibitis some HCV protease mutaions such as the R155K mutation associated with other protease inhibitors currently in studies in patients. The drug is a potent inhibitor of wild-type HCV-P in biochemical (IC50=0.4nM) and replicon cellular (EC50=4.6nM) in vitro assays. The drug works in a unique way and suggests efficacy against HCV protease inhibitors. The resistance profile of the drug is being studied and they said it would be presented at AASLD.
The 3rd talk this morning is by G Wang from Enanta who is developing HCV protease inhibitors along with Abbott. They have a series of compounds but EA-383 appears to be a lead compound. EA-383 appears potent in vitro and is active against all genotypes but a little better against genotype 1. The drug has a "very" high exposure in the liver and a high liver-plasma concentration and a 600 times higher concentration in the liver than in the plasma, even 24 hours after dosing had a high liver level. He said it is potent against HCV resistant mutants which will be presented next by Krishnan from Abbott.
Preethi Krishnan from Abbott is now presenting on this series of protease inhibitors. These are different types of HCV protease inhibitors than others in development. EA-383 has a higher genetic barrier than other compounds to resistance to the usual mutations. In vitro ES-383 showed about a 4.5 log viral log reduction. In vitro they showed data that EA-383 was more potent than ITMN-191 in genotype 1. It appears more potent in vitro against geno 1A. the data presented reported EA-383 was active against some HCV protease mutations but not other mutations. So I asked the presenter about that - if a patient fails a protease inhibitor with several protease mutations EA-383 did not appear to be able to suppress such a virus. In response Krishnan said if they could reach high blood levels with this drug perhaps they could suppress resistant viruses, and if a patient fails with only the mutation against which EA-383 is active then EA-383 could be potently active. Then Dale Kempf spoke and I think he suggested the 155 and 168, the usual HCV PI mutations could be problematic.
FDA Loosens Up HCV Drug Development
FDA Loosens Up HCV Drug Development - HCV Boston Meeting June 27, 2009
4th International Workshop on Hepatitis C
Resistance and New Compounds 25-26 June 2009, Boston, MA USA
Reported by Jules Levin
At the HCV meeting in Boston, Kim Struble from the FDA delivered a talk on expectations regarding HCV clinical drug development but the big news was that she announced the FDA loosened up a requirement for new HCV compounds regarding pre-clinical animal studies. Previously the FDA required before conducting a study of a combination of 2 oral HCV drugs in patients a company would be required to conduct an animal study giving the animal both of the 2 oral drugs in combination for 3 months. That has been loosened up so now a company only has to conduct a 3 month study giving an animal 1 oral for 3 months and an animal the 2nd oral for 3 months, in other words you don't have to give an animal both orals in combination together for 3 months, you only have to do 3 months of monotherapy for each oral drug independently. The Roche INFORM Study was conducted overseas because of that prior FDA requirement and researchers felt constricted by this rule, so now this loosening of that requirement should help to facilitate drug development. Also the Dr Struble encouraged companies to contact the FDA to inquire about questions they may have drug development rather than presuming they know the requirements, it seems often a company will assume they understand what is expected of them, but they are sometimes wrong. In a question from the audience about EPO Dr Struble appeared to me to leave the door open to EPO use. Another question from the audience asked about biopsy vs non-invasive testing and Dr struble said non-invasive tests are not yet validated so biopsy is required.
4th International Workshop on Hepatitis C
Resistance and New Compounds 25-26 June 2009, Boston, MA USA
Reported by Jules Levin
At the HCV meeting in Boston, Kim Struble from the FDA delivered a talk on expectations regarding HCV clinical drug development but the big news was that she announced the FDA loosened up a requirement for new HCV compounds regarding pre-clinical animal studies. Previously the FDA required before conducting a study of a combination of 2 oral HCV drugs in patients a company would be required to conduct an animal study giving the animal both of the 2 oral drugs in combination for 3 months. That has been loosened up so now a company only has to conduct a 3 month study giving an animal 1 oral for 3 months and an animal the 2nd oral for 3 months, in other words you don't have to give an animal both orals in combination together for 3 months, you only have to do 3 months of monotherapy for each oral drug independently. The Roche INFORM Study was conducted overseas because of that prior FDA requirement and researchers felt constricted by this rule, so now this loosening of that requirement should help to facilitate drug development. Also the Dr Struble encouraged companies to contact the FDA to inquire about questions they may have drug development rather than presuming they know the requirements, it seems often a company will assume they understand what is expected of them, but they are sometimes wrong. In a question from the audience about EPO Dr Struble appeared to me to leave the door open to EPO use. Another question from the audience asked about biopsy vs non-invasive testing and Dr struble said non-invasive tests are not yet validated so biopsy is required.
Biolex Therapeutics Announces Completion of Enrollment in SELECT-2 Phase 2b Trial
Biolex Therapeutics Announces Completion of Enrollment in SELECT-2 Phase 2b Trial of Locteron(R) in Chronic Hepatitis C
PITTSBORO, NC -- 06/29/09 -- Biolex Therapeutics, Inc. announced today that it has completed patient enrollment in the SELECT-2 Phase 2b trial of its lead product candidate Locteron® for the treatment of chronic hepatitis C. Locteron, controlled-release interferon alpha 2b, is designed to improve patient care by providing a more convenient once-every-two week dosing schedule and by reducing the side effects, including flu-like symptoms, associated with pegylated interferons, the current standard of care.
The Phase 2b trial is being conducted in the United States and Europe in over 100 treatment-naïve, genotype-1, chronic hepatitis C patients. Patients were randomized into one of four dosing cohorts, the 320, 480 or 640 µg dose of Locteron (administered once every two weeks) or a control arm consisting of PEG-Intron® (1.5 µg/kg, administered every week), with all patients receiving weight-based ribavirin. Patients will be treated for 48 weeks and will be followed for an additional 24 weeks to determine the sustained virologic response (SVR) rate. The interim results after 12 weeks of treatment are expected to be used as the basis for the selection of the Locteron dose(s) for Phase 3 trials.
"We are pleased with the response to the SELECT-2 Phase 2b trial and the fact that we were able to rapidly complete enrollment using substantially less clinical sites than we originally anticipated," said Mr. Jan Turek, Biolex's President and Chief Executive Officer. "Locteron is the only controlled-release interferon alpha under development and research to date suggests that this attribute may reduce side effects and has the potential to improve patient compliance and to reduce discontinuation rates. Extensive market research recently completed confirms that there is a substantial commercial opportunity for Locteron if a tolerability advantage is demonstrated in more advanced clinical testing. We look forward to receiving key results from SELECT-2 during the fourth quarter of this year."
Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.
Locteron Overview
Locteron is a controlled-release interferon alpha designed to improve patient care in the treatment of hepatitis C through a more favorable side-effect profile and dosing convenience compared to existing pegylated interferon products. In contrast to Locteron's controlled-release mechanism, the currently approved products, Pegasys® and PEG-Intron, and the investigational product Albuferon®, are immediate-release products that lack a controlled-release mechanism. Interferon alpha serves as the foundation of current combination therapy for hepatitis C patients, and all major hepatitis C drug candidates currently in clinical trials are being studied in combination with interferon alpha. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons and Albuferon. This controlled-release mechanism is designed to reduce the frequency, duration and severity of side effects, including flu-like symptoms, commonly experienced by patients treated with pegylated interferons and with Albuferon.
About Biolex Therapeutics
Biolex is a clinical-stage biopharmaceutical company that uses its patented LEX System(SM) to develop hard-to-make therapeutic proteins and to optimize monoclonal antibodies. The LEX System is a novel technology that genetically transforms the aquatic plant Lemna to enable the production of biologic product candidates. The company's product candidates are designed to provide superior efficacy/tolerability profiles and to address large, proven pharmaceutical markets. Biolex's lead product candidate, Locteron®, is in Phase 2b clinical testing for the treatment of chronic hepatitis C. Biolex has also developed two other product candidates that capitalize on the benefits of the LEX System which it is advancing toward clinical trials: BLX-155, a direct-acting thrombolytic designed to dissolve blood clots in patients; and BLX-301, a humanized anti-CD20 antibody it is optimizing for the treatment of non-Hodgkin's B-cell lymphoma and other diseases.
Contacts:
Media:
Michelle Linn
Linnden Communications
508-362-3087
Email Contact
Investors:
Dale Sander
Chief Financial Officer
858-663-6993
Email Contact
PITTSBORO, NC -- 06/29/09 -- Biolex Therapeutics, Inc. announced today that it has completed patient enrollment in the SELECT-2 Phase 2b trial of its lead product candidate Locteron® for the treatment of chronic hepatitis C. Locteron, controlled-release interferon alpha 2b, is designed to improve patient care by providing a more convenient once-every-two week dosing schedule and by reducing the side effects, including flu-like symptoms, associated with pegylated interferons, the current standard of care.
The Phase 2b trial is being conducted in the United States and Europe in over 100 treatment-naïve, genotype-1, chronic hepatitis C patients. Patients were randomized into one of four dosing cohorts, the 320, 480 or 640 µg dose of Locteron (administered once every two weeks) or a control arm consisting of PEG-Intron® (1.5 µg/kg, administered every week), with all patients receiving weight-based ribavirin. Patients will be treated for 48 weeks and will be followed for an additional 24 weeks to determine the sustained virologic response (SVR) rate. The interim results after 12 weeks of treatment are expected to be used as the basis for the selection of the Locteron dose(s) for Phase 3 trials.
"We are pleased with the response to the SELECT-2 Phase 2b trial and the fact that we were able to rapidly complete enrollment using substantially less clinical sites than we originally anticipated," said Mr. Jan Turek, Biolex's President and Chief Executive Officer. "Locteron is the only controlled-release interferon alpha under development and research to date suggests that this attribute may reduce side effects and has the potential to improve patient compliance and to reduce discontinuation rates. Extensive market research recently completed confirms that there is a substantial commercial opportunity for Locteron if a tolerability advantage is demonstrated in more advanced clinical testing. We look forward to receiving key results from SELECT-2 during the fourth quarter of this year."
Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.
Locteron Overview
Locteron is a controlled-release interferon alpha designed to improve patient care in the treatment of hepatitis C through a more favorable side-effect profile and dosing convenience compared to existing pegylated interferon products. In contrast to Locteron's controlled-release mechanism, the currently approved products, Pegasys® and PEG-Intron, and the investigational product Albuferon®, are immediate-release products that lack a controlled-release mechanism. Interferon alpha serves as the foundation of current combination therapy for hepatitis C patients, and all major hepatitis C drug candidates currently in clinical trials are being studied in combination with interferon alpha. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons and Albuferon. This controlled-release mechanism is designed to reduce the frequency, duration and severity of side effects, including flu-like symptoms, commonly experienced by patients treated with pegylated interferons and with Albuferon.
About Biolex Therapeutics
Biolex is a clinical-stage biopharmaceutical company that uses its patented LEX System(SM) to develop hard-to-make therapeutic proteins and to optimize monoclonal antibodies. The LEX System is a novel technology that genetically transforms the aquatic plant Lemna to enable the production of biologic product candidates. The company's product candidates are designed to provide superior efficacy/tolerability profiles and to address large, proven pharmaceutical markets. Biolex's lead product candidate, Locteron®, is in Phase 2b clinical testing for the treatment of chronic hepatitis C. Biolex has also developed two other product candidates that capitalize on the benefits of the LEX System which it is advancing toward clinical trials: BLX-155, a direct-acting thrombolytic designed to dissolve blood clots in patients; and BLX-301, a humanized anti-CD20 antibody it is optimizing for the treatment of non-Hodgkin's B-cell lymphoma and other diseases.
Contacts:
Media:
Michelle Linn
Linnden Communications
508-362-3087
Email Contact
Investors:
Dale Sander
Chief Financial Officer
858-663-6993
Email Contact
Achillion Announces First-in-Human Dosing of ACH-1625 for Treatment of Hepatitis C
Achillion Announces First-in-Human Dosing of ACH-1625 for Treatment of Hepatitis C
Source: Achillion Pharmaceuticals, Inc
NEW HAVEN, Conn., June 29, 2009 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN), a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today announced that the Company has begun dosing in a Phase I clinical trial of ACH-1625, a protease inhibitor for the treatment of hepatitis C virus (HCV) infection.
The Phase I clinical trial is a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-1625 after single and multiple ascending oral doses in healthy volunteers, and oral ascending repeat doses in subjects with hepatitis C infection. The trial will take place in Europe and is designed to enroll 54 subjects including both healthy volunteers and HCV-infected patients. Data from the trial are anticipated to be announced later this year.
ACH-1625 is a potent small molecule inhibitor of HCV protease, an enzyme necessary for viral replication. The drug candidate was discovered and is being advanced by Achillion.
"This first-in-human clinical trial will be instrumental in establishing the safety profile of ACH-1625 in humans," stated Elizabeth A. Olek, D.O., Vice President and Chief Medical Officer of Achillion. "Importantly, it will also provide Achillion with preliminary efficacy data and important dose selection information for subsequent Phase II trials. We believe ACH-1625 has the potential to offer a convenient dosing schedule and an improved safety and tolerability profile compared to currently available treatments for HCV-infected patients."
"We are very excited to take ACH-1625 into the clinic to test the compound's safety and efficacy in humans," said Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "With its potency and safety profile in preclinical studies, and its potential for once-daily dosing, we are eager to advance what we hope will be a best-in-class candidate."
About ACH-1625
ACH-1625 is an HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies ACH-1625 has demonstrated potency, unique pharmacokinetic properties and a safe in vivo profile even at very high doses.
With its rapid and extensive partitioning to the liver, as well as high liver/plasma ratios demonstrated in vivo, Achillion believes that ACH-1625 can be dosed on a convenient schedule at a relatively low dosage. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50 ~1nM. High safety margins have been established in both single ascending dose and repeat dose studies in vivo. Overall, Achillion believes the compound is well tolerated with minimal side effects.
About HCV
The hepatitis C virus (HCV) is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80% of individuals become chronically infected following exposure. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, injectable route of administration and high cost.
About Achillion
Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease -- hepatitis C, resistant bacterial infections and HIV. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including statements with respect to Achillion's expectations regarding the results of ongoing clinical trials, timing and duration of clinical trials, Achillion's expectations regarding the release of data from ongoing clinical trials, and enforceability of patents. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: uncertainties relating to results of clinical trials, unexpected regulatory actions or delays, and Achillion's ability to obtain additional funding required to conduct its research, development and commercialization activities along with Achillion's ability to attract and develop potential collaboration relationships. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2008.
All forward-looking statements reflect Achillion's expectations only as of the date of this release and should not be relied upon as reflecting Achillion's views, expectations or beliefs at any date subsequent to the date of this release. Achillion anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Achillion may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.
ACHN-G
CONTACT: Achillion Pharmaceuticals, Inc.
Mary Kay Fenton
(203) 624-7000
mfenton@achillion.com
Lippert/Heilshorn & Associates
Investors:
Anne Marie Fields
(212) 838-3777
afields@lhai.com
Bruce Voss
(310) 691-7100
bvoss@lhai.com
Media:
Jules Abraham
(212) 838-3777
jabraham@lhai.com
Source: Achillion Pharmaceuticals, Inc
NEW HAVEN, Conn., June 29, 2009 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN), a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today announced that the Company has begun dosing in a Phase I clinical trial of ACH-1625, a protease inhibitor for the treatment of hepatitis C virus (HCV) infection.
The Phase I clinical trial is a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-1625 after single and multiple ascending oral doses in healthy volunteers, and oral ascending repeat doses in subjects with hepatitis C infection. The trial will take place in Europe and is designed to enroll 54 subjects including both healthy volunteers and HCV-infected patients. Data from the trial are anticipated to be announced later this year.
ACH-1625 is a potent small molecule inhibitor of HCV protease, an enzyme necessary for viral replication. The drug candidate was discovered and is being advanced by Achillion.
"This first-in-human clinical trial will be instrumental in establishing the safety profile of ACH-1625 in humans," stated Elizabeth A. Olek, D.O., Vice President and Chief Medical Officer of Achillion. "Importantly, it will also provide Achillion with preliminary efficacy data and important dose selection information for subsequent Phase II trials. We believe ACH-1625 has the potential to offer a convenient dosing schedule and an improved safety and tolerability profile compared to currently available treatments for HCV-infected patients."
"We are very excited to take ACH-1625 into the clinic to test the compound's safety and efficacy in humans," said Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "With its potency and safety profile in preclinical studies, and its potential for once-daily dosing, we are eager to advance what we hope will be a best-in-class candidate."
About ACH-1625
ACH-1625 is an HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies ACH-1625 has demonstrated potency, unique pharmacokinetic properties and a safe in vivo profile even at very high doses.
With its rapid and extensive partitioning to the liver, as well as high liver/plasma ratios demonstrated in vivo, Achillion believes that ACH-1625 can be dosed on a convenient schedule at a relatively low dosage. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50 ~1nM. High safety margins have been established in both single ascending dose and repeat dose studies in vivo. Overall, Achillion believes the compound is well tolerated with minimal side effects.
About HCV
The hepatitis C virus (HCV) is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80% of individuals become chronically infected following exposure. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, injectable route of administration and high cost.
About Achillion
Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease -- hepatitis C, resistant bacterial infections and HIV. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including statements with respect to Achillion's expectations regarding the results of ongoing clinical trials, timing and duration of clinical trials, Achillion's expectations regarding the release of data from ongoing clinical trials, and enforceability of patents. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: uncertainties relating to results of clinical trials, unexpected regulatory actions or delays, and Achillion's ability to obtain additional funding required to conduct its research, development and commercialization activities along with Achillion's ability to attract and develop potential collaboration relationships. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2008.
All forward-looking statements reflect Achillion's expectations only as of the date of this release and should not be relied upon as reflecting Achillion's views, expectations or beliefs at any date subsequent to the date of this release. Achillion anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Achillion may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.
ACHN-G
CONTACT: Achillion Pharmaceuticals, Inc.
Mary Kay Fenton
(203) 624-7000
mfenton@achillion.com
Lippert/Heilshorn & Associates
Investors:
Anne Marie Fields
(212) 838-3777
afields@lhai.com
Bruce Voss
(310) 691-7100
bvoss@lhai.com
Media:
Jules Abraham
(212) 838-3777
jabraham@lhai.com
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