Achillion Announces Additional Proof-of-Concept Data With ACH-2684 for the Treatment of Hepatitis C (ACHN)

Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) is an innovative biopharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. The Company's highly skilled and experienced 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 - HCV and resistant bacterial infections. 

The Company has "reported proof-of-concept data from a Phase 1b clinical trial demonstrating that patients with chronic hepatitis C (HCV) genotype 1 (GT 1) treated with ACH-2684, a second-generation protease inhibitor, achieved a mean maximum 3.73 log10 reduction in HCV RNA after three-day 400 mg monotherapy with once-daily (QD) dosing. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with HCV."

Michael D. Kishbauch, President and Chief Executive Officer of Achillion, commented, 

"We believe ACH-2684, with its potent antiviral activity achieved without boosting and once-daily dosing, is one of the most intriguing protease inhibitors in clinical development for the treatment of HCV. As we continue to focus our efforts on advancing our internally developed all-oral, interferon-free HCV regimen consisting of ACH-1625, our next generation protease inhibitor, in combination with ACH-3102, a second generation pan-genotypic NS5A inhibitor, we believe that the profile of ACH-2684 provides a significant strategic and therapeutic option for potential combinations with either ACH-3102 or other direct-acting antiviral agents." 

Read more at ir.achillion.com. 

ACH-3102 Receives Fast Track Designation From the FDA for the Treatment of Chronic Hepatitis C (ACHN)

Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) 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 including HCV and resistant bacterial infections. 

The Company announced that it has received a Fast Track designation from the U.S. Food and Drug Administration (FDA) for ACH-3102 "as part of an interferon-free regimen for the treatment of chronic hepatitis C (HCV). ACH-3102 is a pan-genotypic second-generation NS5A inhibitor against HCV that was discovered by Achillion and is currently being evaluated in a Phase 1 clinical trial."

Fast Track designation was requested for ACH-3102 for its potential to provide:

• "Improved safety as compared to the current standard of care
• Potential for development in a once daily interferon-free fixed dose combination
• Potent antiviral activity in vitro against HCV genotypes 1 through 6
• Low potential for drug-drug interactions and therefore greater potential to treat HCV patients with comorbidities, co-infected with HIV, or pre- or post-liver transplantation."

ACH-3102 is "a structurally distinct small molecule compound that has demonstrated potent inhibition of the NS5A protein across all genotypes of HCV in preclinical studies. Furthermore, the unique chemical structure of ACH-3102 has resulted in enhanced potency in vitro against resistant mutants that have emerged during clinical studies with first generation NS5A inhibitors."

President and Chief Executive Officer of Achillion Michael Kishbauch commented,

"We are very pleased with the granting of a Fast Track designation for ACH-3102, which we believe highlights this second-generation NS5A inhibitor's attributes that include pan-genotypic coverage of HCV and potential for maintained activity against NS5A mutant strains of HCV. We are excited to leverage the superior profile of ACH-3102 in combination with our Phase 2 protease inhibitor, ACH-1625, as we seek to create an optimized, potentially best-in-class potent, well-tolerated, once-daily regimen to treat HCV, which will enter combination studies during the third quarter of this year."

Read more at Nasdaq.com. 

Achillion ($ACHN): Mixed Reaction from Analysts, UBS Downgrades

UBS comments on the full data from the phase 2 trial of ACH-1625 and sees the data as suggestive of a safety signal with LFT events that appear dose dependent.

• UBS notes a potential potency issue as well
• Target remains $7
• Analyst is Matthew Harrison

Achillion Pharmaceuticals (NASDAQ: ACHN) today announed announced at the Annual Meeting of the European Association for the Study of the Liver (EASL) International Liver Congress that in the second segment of its Phase 2a trial of ACH-1625, 94 to 100% of patients with treatment naïve genotype 1 chronic hepatitis C virus (HCV) achieved a complete early virologic response (cEVR) after 12 weeks of treatment with ACH-1625 in combination with pegylated interferon alfa-2a and ribavirin (P/R).

• ACH-1625 in combination with P/R for up to 12 weeks was safe and well tolerated and produced high viral response rates regardless of dose level or IL28B genotype status.
• Michael Kishbauch, President and CEO of Achillion, said, "As we finalize this Phase 2 trial and report on SVR later this year, we are now focused on initiating our all-oral program for the treatment of HCV. With the recent submission of an IND for ACH-3102, our second-generation NS5A inhibitor, we look forward to initiating its Phase 1 program this quarter and rapidly advancing toward a therapeutic, interferon-free combination trial evaluating ACH-1625 plus ACH-3102 during Q4 of this year."
• In Segment 2 of this Phase 2a trial, a total of 58 subjects with HCV were enrolled, randomized and stratified by IL28B genotype, including CT and TT, which is a marker of a patient's responsiveness to interferon, to receive one of three doses of once-daily ACH-1625 (200 mg, 400 mg or 800 mg) in combination with P/R for 12 weeks of therapy.
  • Of the patients enrolled, the majority had HCV genotype 1a (n=35 (60%)), with remaining patients having HCV genotype 1B (n=20) or genotype 1 (n=3). Approximately 71% of the patients were IL28B genotype CT/TT, the more difficult to treat mutation, 64% were male and 17% were African American. No viral breakthroughs were observed during treatment. Results demonstrated rapid virological response (RVR) at week 4, cEVR and end of treatment (EOT) responses for patients returning for EOT visit to date can be viewed in a table here.
  • Safety results from both segments of the trial were similar to those observed and previously reported during clinical trials of ACH-1625.
• In a separate poster presentation, the clinical virology of NS3 variants from patients enrolled in Segment 1 of the Phase 2a clinical trial evaluating multiple ascending doses of ACH-1625 in combination with P/R was presented.
  • Sequencing of baseline to post-treatment samples revealed that there were no mutations at loci 155, 156, or 168 of NS3 protease, which represent common mutations that may confer resistance to protease inhibitors.

Brean Murray, Carret on Achillion Pharmaceuticals - $ACHN

Brian Skorney of Brean Murray put out the following on Achillion Pharmaceuticals (ACHN, $7.92, Buy, $20 Target Price):

"Defending ACHN - GS-7977 Data Is Great but ACH-1625 Can Be Head-to-Head Competitive With 7977 or Be the Best Option To Combine With 7977

We believe the sharp decline in ACHN shares is being driven from a superficial read-through from the GILD/BMS data. We believe that a protease inhibitor is not a necessary component of an all-oral regimen. However, we believe that the valuation assumes that a protease inhibitor is also not sufficient in an oral combination that does not include a nuc. Abbott (ABT, $59.27, Hold) has already demonstrated that a potent PI with a differentiated resistance profile can be an anchor for an all-oral regimen. We believe the upcoming oral presentations of Abbott's PILOT (today) and COPILOT (Saturday) studies will reaffirm this thesis.

7977/052 Combo Data Actually Supports ACH-1625 Potential. We believe the high SVR rates seen in the 7977/052 combo, particularly in Gt 2/3 patients, actually supports the potential of ACH-1625 as it indicates that if you have one potent antiviral with a high barrier to resistance, you can get by with a weaker agent with a low barrier to resistance. BMS052 readily selects for resistance and is 10-15x less potent in Gt. 2/3 compared to Gt. 1b. We believe ACH-1625 is one of only four drugs in clinical development that could be effectively substituted for GS-7977 in this combo and show similar results – the others being INX-189, MK-5172, and ABT-450/r. We believe Achillion will successfully run this experiment with its own NS5a inhibitor, ACH-3102, later this year."