Achillion Announces Positive Once-Daily Dosing Results With ACH-1625 to Treat Hepatitis C

Achillion Announces Positive Once-Daily Dosing Results With ACH-1625 to Treat Hepatitis C
May 11, 2010 (GlobeNewswire via COMTEX News Network) --

Once-Daily Dose Achieves 3.81 log10 Viral Load Reduction With Continued

Safety and Tolerability



Conference Call Begins Wednesday, May 12 at 1:15 p.m. Eastern Time



NEW HAVEN, Conn., May 11, 2010 (GLOBE NEWSWIRE) -- Achillion
Pharmaceuticals, Inc. (Nasdaq:ACHN) today reported additional
preliminary data from its Phase 1b clinical trial of ACH-1625, which
demonstrated that both the third and fourth patient cohorts receiving
treatment with ACH-1625 achieved meaningful reductions in HCV RNA after
five-day monotherapy, with continued safety and tolerability in
patients with hepatitis C (HCV). ACH-1625 is an inhibitor of HCV NS3
protease that was discovered and is being developed by Achillion.

Third Dosing Cohort Results (200mg Twice Daily)

Subjects in the third cohort of HCV-infected patients received doses of 200mg twice-daily (n=9, randomized to 6 active drug, 3 placebo) for five days. Preliminary results showed that a mean maximum reduction in viral load of 3.86 log10 was achieved in the treatment group, as compared to a mean rise of 0.16 log10 in the placebo group. All subjects in the treatment group had viral load decline greater than 3.0 log10. Mean alanine aminotransferase (ALT) levels decreased over the treatment period and continued to show decline at day 12. Safety results from this dosing group were similar to those observed in previous segments of the trial. There were no serious adverse events, and no clinically significant changes in vital signs, electrocardiograms or laboratory evaluations. All reported adverse events in patients receiving ACH-1625 were classified as mild or moderate and were transient. As seen in previous dosing cohorts, sustained viral suppression was noted with patients maintaining a mean reduction of 1.65 log10 from baseline through day 12, seven days after dosing was completed and the last day of viral load measurement in the study.

Fourth Dosing Cohort Results (600mg Once Daily)

Subjects in the fourth cohort of HCV-infected patients received doses of 600mg once-daily (n=8, randomized to 6 active drug, 2 placebo) for five days. Preliminary results showed that a mean maximum reduction in viral load of 3.81 log10 was achieved in the treatment group, as compared to a mean rise of 0.24 log10 in the placebo group. All subjects in the treatment group had viral load decline greater than 3.0 log10. Mean alanine aminotransferase (ALT) levels decreased over the treatment period and continued to show decline at day 12. Safety results from this dosing group were similar to those observed in previous segments of the trial. There was one non-drug-related serious adverse event, a bone fracture in a patient receiving placebo. There were no clinically significant changes in vital signs, electrocardiograms or laboratory evaluations. All reported adverse events in patients receiving ACH-1625 were classified as mild or moderate and were transient. Again, sustained viral suppression was noted in this dosing cohort of HCV-infected subjects, with patients maintaining a mean reduction of 2.19 log10 from baseline through day 12, seven days after dosing was completed and the last day of viral load measurement in the study.

"We continue to be pleased with the robust results from these additional cohorts of our ACH-1625 Phase 1b trial with HCV-infected patients," said Michael D. Kishbauch, Achillion's President and Chief Executive Officer. "It is impressive that at all dose levels ACH-1625 has shown meaningful viral load reduction and sustained viral suppression post treatment course. Importantly, we believe the results from these last two cohorts demonstrated that ACH-1625 was effective at a lower dosing level and in a once-daily dose, features that distinguish our drug and suggest it could offer improvements over other protease inhibitors currently in development."

He continued, "In summary, these data round out the phase 1b program for ACH-1625 very favorably. If these results are sustained through further development, we believe the combination of potency, safety/tolerability, dosing flexibility and durability of effect will position ACH-1625 as a potential best-in-class protease inhibitor, while strategically enhancing Achillion for a variety of options. We remain very encouraged by these compelling results and look forward to advancing the drug into Phase 2 studies in the coming months."

Conference Call
The Company will host a teleconference to discuss these clinical trial results on Wednesday, May 12, 2010 at 1:15 p.m. Eastern Daylight Time. Along with Achillion management, Douglas Dietrich, M.D. of Mount Sinai Medical Center, New York, will participate in the call. The call may be joined via telephone by dialing 800-776-0420 or 913-312-0968 (for international participants) at least 5 minutes prior to the start of the call and using the conference confirmation code 6476067. An audio replay will be available through midnight on May 17, 2010 by dialing (888) 203-1112 or (719) 457-0820 (international) and using the conference confirmation code 6476067.

A live audio webcast of the call will also be available on the "Investor Relations" section of the company's website, www.achillion.com. An archived audio webcast will be available on the Achillion website approximately two hours after the event and will be archived for three months.

Previous Dosing Cohort Results

In Phase 1a safety studies with ACH-1625, subjects in the single ascending dose (SAD) segment of the study received doses ranging from 50mg to 2000mg. Subjects in the Phase 1a multiple ascending dose (MAD) segment of the study received five days of ACH-1625 up to a maximal dose of 2000mg per day. Preliminary data from the SAD and MAD trial segments demonstrated ACH-1625 was well tolerated at all doses and there were no serious adverse events, and no clinically significant changes in vital signs, electrocardiograms or laboratory evaluations. All reported adverse events were classified as mild or moderate, were transient and showed no apparent dose relationship.

In December 2009, Achillion announced proof-of-concept data from the first dosing cohort in the Phase 1b study. Subjects in this cohort of HCV-infected patients received doses of 600mg twice-daily (n=9, randomized to 6 active drug, 3 placebo). Preliminary results showed that a mean reduction in viral load of 3.94 log10 was achieved in the treatment group, as compared to a mean reduction of 0.22 log10 in the placebo group. All subjects in the treatment group had viral load decline between 3.0 and 4.5 log10, and two subjects reached undetectable levels of HCV RNA. Safety results from this dosing group were similar to those observed in the Phase 1a segment of the trial. There were no serious adverse events, and no clinically significant changes in vital signs, electrocardiograms or laboratory evaluations. All reported adverse events were classified as mild or moderate, were transient and showed no apparent dose relationship. Furthermore, all patients had viral loads that remained suppressed for at least seven days after dosing was completed, maintaining a mean reduction of more than 2.0 log10 from baseline through day 12, the last day of viral load measurement in the study.

In January 2010, Achillion announced results from the second dosing cohort in the Phase 1b study. HCV-infected subjects in this cohort (n=9, randomized to 6 active drug, 3 placebo) received doses of 500mg of ACH-1625 twice-daily. Preliminary results showed that a mean reduction in viral load of 4.25 log10 was achieved in the treatment group, as compared to a mean reduction of 0.29 log10 in the placebo group. Safety results from this dosing group were similar to those observed in both the Phase 1a segment of the trial and in the first cohort of HCV-infected subjects. Sustained viral suppression was also similar to the first cohort of HCV-infected subjects, with patients maintaining a mean reduction of more than 3.0 log10 from baseline through day 12, seven days after dosing was completed and the last day of viral load measurement in the study.

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 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. ACH-1625 has rapid and extensive partitioning to the liver, as well as high liver/plasma ratios. 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 approximately 1nM.
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Achillion's 'Very Promising' New Drug for Hepatitis C
http://www.dailyfinance.com
Posted 4:45 PM 04/14/10

Achillion (ACHN), a small biopharmaceutical that focuses on infectious disease, knows the story about hepatitis C very well. A liver disease caused by the hepatitis C virus (HCV), viral hepatitis is the leading cause of liver cancer and the most common reason for a liver transplant. An estimated 4.1 million Americans are infected with the HCV with 17,000 new cases annually. And the disease causes an estimated 10,000 to 12,000 deaths annually in the U.S.

Currently, few therapeutic options exist, and that's where Achillion comes in. Existing treatments aren't always effective and have considerable side effects. Achillion is among the drug companies developing a new class of drugs known as protease inhibitors, which target an enzyme that breaks down the protein and facilitates production of the new viruses. By blocking the virus's functioning, protease inhibitors interfere with continued infection.

Says Achillion CEO Mike Kishbauch (pictured): "Our lead candidate appears to be a very promising compound and has been a stimulus for the company's growth." That candidate is called ACH-1625 -- "a potent inhibitor of hepatitis C virus protease that a recent panel of HCV clinical experts called the best and cleanest looking new direct antiviral in development today," says Kishbauch.

Achillion is in the process of finishing a Phase 1 proof-of-concept study. The company will be presenting more in-depth details about these studies at the International Liver Conference in Vienna, Austria, on Thursday and Friday. It will report additional results a few weeks after the conference.

Four Advantages

Realizing that some of its competitors are farther ahead with their protease inhibitor development -- like Vertex's (VRTX) telaprevir and Merck's (MRK) boceprevir -- Achillion expects that ACH-1625's demonstrated potency and safety will be enough to "differentiate it from the pack and push it ahead of competition once it hits the market."

So far, says Kishbauch, ACH-1625 has shown four significant characteristics over competitors "that could make it a best in class." First, he says, is "its potency in reducing the [amount of virus] is at the top end vs. any of the other similar drugs discovered. Second, other first-generation protease inhibitors have safey and tolerability concerns such as rashes and anemia. ACH-1625's safety and tolerability profile is so far among the cleanest of any the drugs in development.

"Third, ACH-1625 appears likely to be dosable at once-a-day, while first-generation drugs will need to be dosed every 8 to 12 hours. Fourth, one of the surprisingly serendipitous finding is its durability, meaning that once you discontinue dosing, the drug continues to have antiviral effect up to seven days after discontinuation of dosing. Other drugs return to baseline virus levels after 24-48 hours. This is important, in particular, with missed doses."

Achillion has three additional hepatitis C drugs: ACH-1095 has been in partnership with Gilead Sciences (GILD) since 2004; ACH-2676 is considered the backup to ACH-1625; and ACH-2684, which Kishbauch says "appears to be a hundred times more potent and works against resistant mutations and the full range of the six genotypes of the hepatitis C virus."

Big Pharma and Wall Street Are Interested

"We are in fairly heavy discussions of partnership of ACH-1625," Kishbauch says. "There is a great deal of interest among the significant players of the field, and it's highly likely that we will partner with one of the major players in hepatitis C within the next year if not sooner."

Kishbauch explains reason for that interest: "Under any kind of reasonable pricing assumption, most cast the value of the market for these antivirals at $8 billion to $10 billion. Even with modest penetration of several players, the products could be worth $1 billion or greater."

"We are in a position to conduct those discussions at a measured pace," he says. CFO Mary Kay Fenton explains, "We completed an offering in January and raised $25 million to fund advancement of our core assets -- finish Phase 1 and launch Phase 2 at the end of the year."

Wall Street seems interested as well. "We were 2.5 times oversubscribed on the offer," Fenton says, who adds that a "who's who of investors came in to take major pieces."

Seconding the Motion

Several analysts are indeed sounding bullish. Following the Phase 1 results, analysts at National Securities wrote: "A number of critical pieces of scientific evidence suggests that the ACHN-1625 profile is that of a second-generation protease Inhibitor vs. the first-generation molecules now in the late stages of clinical development."

Analysts at Oppenheimer wrote: "Given the results from the first cohort, and preclinical results, we would expect ACH-1625 to continue to show strong antiviral activity as additional data become available." And analysts at Canccord Adams called the results "impressive" and wrote in a note: "On the heels of these positive data, we expect ongoing partnership discussions for ACH-1625 to gain further momentum."

Achillion's share price has nearly doubled over the last year, and is now around $3 per share. But on average analysts expect it to at least double over the next year. Says Kishbauch: "The company has business and scientific momentum at this point." However, investors should remember that like with so many small biotechs, the risks are great -- and those early-stage compounds may never pan out.