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Impressive interim results
NEW HAVEN, Conn.—Achillion Pharmaceuticals Inc. had good news to share recently as it announced new interim results from a Phase 2a study, which is being conducted by Alios BioPharma Inc., part of the Janssen Pharmaceutical Companies. The ongoing study is aiming to confirm the required dose and treatment duration for an all-oral combination regimen containing odalasvir (ODV) and AL-335 with or without simeprevir (SMV) for durations of eight or six weeks of treatment in treatment-naïve patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection—specifically the safety, efficacy and pharmacokinetics of the combinations. Achillion and Janssen began a collaboration in May 2015 for the development and commercialization of one or more of Achillion's HCV assets.
The data were shared as part of the abstracts released for the European Association for the Study of the Liver (EASL) Special Conference held later this month. Twenty patients were treated in cohort 1—which featured the combination of odalasvir (50mg QD), AL-335 (400mg QD) and simeprevir (100mg QD) for eight weeks—and of those, 100 percent remained HCV RNA undetectable 24 weeks after completing therapy. Cohort 2 also featured 20 patients, these treated with the dual combination of odalasvir (50mg QOD) and AL-335 (800mg QD) for eight weeks—for this group, 90 percent remained HCV RNA undetectable 12 weeks after finishing therapy.
Additional participants were enrolled into two other cohorts—cohorts 3 and 4—in which they received adjusted doses of the same triplet combination regimen for either six or eight weeks. In cohort 3, all patients were HCV RNA-negative, and remained HCV RNA undetectable four weeks after completing therapy. For cohort 4, all participants were HCV RNA negative or below the limit of quantitation when treatment concluded.
"We are delighted by the significant progress Janssen has made in advancing the all-oral, short-duration treatment regimen of odalasvir, AL-335 and simeprevir and are impressed with the Phase 2a study results being presented. Based on these interim results, Janssen plans to advance a Phase 2b program for the triple combination to further understand the potential of this 3DAA drug combination to shorten the duration of treatment for patients suffering from HCV," Dr. Milind Deshpande, president and CEO of Achillion, said in a press release. "Despite recent therapeutic advances, we believe there remains a significant unmet need in addressing the global burden of hepatitis C virus in those living with the disease."
All of the combination regimens were generally safe and well tolerated, and the most common adverse events were headache, fatigue and upper respiratory tract infection. Cohort 1 saw a single serious adverse event related to treatment, which resolved when treatment was discontinued.
In light of these results, the combination regimen is being moved forward into a Phase 2b program, which will consist of once-daily odalasvir 25mg, AL-335 800mg and simeprevir 75mg being tested in two multi-center, randomized, open-label studies that will enroll treatment-naive and treatment-experienced non-cirrhotic patients chronically infected with hepatitis C virus genotypes 1, 2, 4, 5 and 6. An expansion of the current Phase 2a study will also take placing, focusing on patients with or without compensated cirrhosis and on patients presenting with HCV genotype 2 and 3 infection.
Achillion's odalasvir (ACH-3102) is a structurally distinct, second-generation NS5A inhibitor. The compound achieved 100-percent sustained virologic response at 12 weeks in a Phase 2 study of genotype 1 HCV patients treated for six weeks with ACH-3102 + sofosbuvir. ACH-3102 has demonstrated a high barrier to the emergence of resistance in several Phase 2 studies. Simeprevir—known commercially as Olysio—is a NS3/4A HCV protease inhibitor developed by Medivir and Janssen Pharmaceutica for treating HCV.
At present, it is estimated that more than 150 million people are infected with HCV globally, 3 million of which are in the United States. Roughly 75 percent of patients with HCV are undiagnosed, which is a leading issue as chronic hepatitis can lead to permanent liver damage, cancer, liver failure or death if left untreated.