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HCV Drug Development: Merck Acquires Idenix, FDA Lifts Sovaprevir Hold

Merck this week announced that it will purchase Idenix, a specialty biopharmaceutical company developing several hepatitis C virus (HCV) drug candidates. In related news, Achillion announced that the U.S. Food and Drug Administration (FDA) has lifted a clinical hold on one of its drugs and a clinical trial of another is now underway.

Two next-generation direct-acting antivirals -- Janssen's HCV protease inhibitor simeprevir (Olysio) and Gilead Sciences' nucleotide polymerase inhibitor sofosbuvir (Sovaldi) -- are now approved in the U.S., while AbbVie's "3D" combo and Bristol Myers-Squibb's daclatasvir are expected by the end of the year. But the race is far from over, and other companies continue to develop additional agents that can be combined in all-oral, interferon-free regimens.

With the acquisition of Idenix, Merck will add the nucleotide polymerase inhibitor pro-drugs IDX21437 and IDX21459, as well as the NS5A replication complex inhibitor samatasvir (IDX719), to its own leading candidates, the protease inhibitor MK-5172 and NS5A inhibitor MK-8742. The company's first-generation protease inhibitor, boceprevir (Victrelis), is falling out of favor as better-tolerated therapies are developed.

Below is an edited excerpt from a June 9 Merck press release announcing the acquisition.

Merck to Acquire Idenix

Acquisition Expands Portfolio of Promising Investigational Therapies for Hepatitis C

Merck (NYSE:MRK), known as MSD outside the United States and Canada, and Idenix Pharmaceuticals, Inc. (NASDAQ: IDIX), today announced that the companies have entered into a definitive agreement under which Merck will acquire Idenix for $24.50 per share in cash. The transaction, which values the purchase of Idenix at approximately $3.85 billion, has been approved by the boards of directors of both companies.

"Idenix has established a promising portfolio of hepatitis C candidates based on its expertise in nucleoside/nucleotide chemistry and prodrug technologies," said Dr. Roger Perlmutter, president, Merck Research Laboratories. "Idenix’s investigational hepatitis C candidates complement our promising therapies in development and will help advance our work to develop a highly effective, once-daily, all oral, ribavirin-free, pan-genotypic regimen that has a duration of treatment as short as possible for millions of patients in need around the world."

Idenix is a biopharmaceutical company engaged in the discovery and development of medicines for the treatment of human viral diseases, whose primary focus is on the development of next-generation oral antiviral therapeutics to treat hepatitis C virus (HCV) infection. The company currently has three HCV drug candidates in clinical development: two nucleotide prodrugs (IDX21437 and IDX21459) and a NS5A inhibitor (samatasvir). These novel candidates are being evaluated for their potential inclusion in the development of all oral, pan-genotypic fixed-dose combination regimens.

"Merck has established a strong legacy of leadership and innovation in treating hepatitis C," said Ron Renaud, Idenix’s President and Chief Executive Officer. "This agreement creates shareholder value by positioning Idenix’s strong portfolio of candidates for future success with a leading healthcare company with the experience and commitment to develop fixed-dosed combinations with the potential to impact the global burden of hepatitis C."

Merck’s research and development portfolio includes several HCV medicines in development, the leading of which is a combination of MK-5172, an investigational HCV NS3/4A protease inhibitor and MK-8742, an investigational HCV NS5A replication complex inhibitor. The combination of these two investigational candidates has received Breakthrough Therapy designation from the U.S. Food and Drug Administration for the treatment of HCV. In April 2014, Merck announced initiation of Phase 3 clinical trials for MK-5172/MK-8742 to evaluate the combination with and without ribavirin in various genotypes and across a broad range of patient populations with chronic HCV. Study information can be found at www.clinicaltrials.gov.

Achillion Hold Lifted

Also this week, Achillion Pharmaceuticals said it has begun treating the first patients in a Phase 1 trial of its nucleotide HCV polymerase inhibitor ACH-3422.

In addition, the company said the FDA has lifted the clinical hold on the company's HCV protease inhibitor sovaprevir (ACH-1625), which was imposed after some healthy volunteers developed unexpected liver enzyme elevations after taking sovaprevir in combination with the ritonavir-boosted HIV protease inhibitor atazanavir (Reyataz) in a drug-drug interaction study.

Below is an edited excerpt from Achillion's June 10 press release describing these developments.

Achillion Announces Initiation of ACH-3422 Dosing in HCV-Infected Patients and Ability to Resume Sovaprevir Clinical Program for the Treatment of Chronic HCV

Initial cohort of HCV-infected patients begin dosing with ACH-3422 for seven days

Clinical trials may continue evaluating 200 mg of sovaprevir for HCV-infected patients

Timelines for reporting proof-of-concept results with ACH-3422, a proprietary uridine-analog nucleotide polymerase inhibitor, during the fall of 2014 and initiating all-oral combination studies by the end of 2014 remain on track

Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced the company has begun dosing ACH-3422, a uridine-analog nucleotide polymerase inhibitor, for seven days in patients with genotype 1 chronic hepatitis C viral infection (HCV) in its ongoing Phase 1 clinical trial. Proof-of-concept results from this trial are expected to be reported during the fall of 2014. Furthermore, Achillion announced today that the U.S. Food and Drug Administration (FDA) has removed the clinical hold on sovaprevir, an NS3/4A protease inhibitor, to permit the conduct of trials in patients with HCV. Sovaprevir doses of 200 mg once daily, the previously evaluated dose that was well-tolerated with clinical activity in two completed Phase 2 studies, may be used in additional therapeutic clinical trials.

"We believe Achillion is uniquely positioned with clinical candidates in each of the nucleotide, NS5A and protease inhibitor categories needed to advance both dual and triple commercially competitive combination therapies that can treat the spectrum of patients with HCV. We remain focused on developing regimens utilizing ACH-3422 and ACH-3102, our second-generation Phase 2 NS5A inhibitor, and the second half of 2014 will feature multiple milestones in that program," commented Milind Deshpande, PhD, President and Chief Executive Officer. "Our HCV pipeline also provides the opportunity to add a NS3/4A protease inhibitor, such as sovaprevir or ACH-2684, in order to explore triple-direct acting antiviral regimens that can potentially shorten treatment durations to less than 8 weeks. We will determine how best to integrate our protease inhibitors into our combination development programs as data from our on-going trials emerge."

"With the start of patient dosing with ACH-3422, our Phase 1 uridine-analog nucleotide, we remain on track to report proof-of-concept results in the fall, and plan on initiating all oral combination studies with ACH-3422 by the end of 2014. We are also very pleased that the effort by the Achillion team, working in collaboration with the FDA, has resulted in this response for the sovaprevir program," commented David Apelian, MD, PhD, Executive Vice President and Chief Medical Officer.

Sovaprevir is a Phase 2 NS3/4A protease inhibitor being developed for the potential treatment of chronic HCV infection. To date, approximately 550 subjects have been exposed to sovaprevir with clinical activity reported in two Phase 2 12-week treatment duration studies, one in combination with pegylated-interferon/ribavirin and one in combination with ACH-3102 in which the combination achieved 100% SVR12 in patients with genotype 1b HCV. The FDA removed the clinical hold to permit the conduct of therapeutic trials with a maximum of 200 mg once daily of sovaprevir in HCV patients and in single dose trials in healthy volunteers, but maintained a partial clinical hold for multiple dose studies that may be conducted in healthy volunteers, requiring prior review and approval of the protocol by the FDA. Achillion expects to continue to work collaboratively with the FDA on the continued clinical development of sovaprevir.

6/11/14

Sources

Merck. Merck to Acquire Idenix. Press release. June 9, 2014.

Achillion Pharmaceuticals. Achillion Announces Initiation of ACH-3422 Dosing in HCV-Infected Patients and Ability to Resume Sovaprevir Clinical Program for the Treatment of Chronic HCV. Press release. June 10, 2014.