Clinical Trials

Date: 2017-02-13

Type of information: Presentation of results at a congress

phase: 2a

Announcement: presentation of results at the Asian Pacific Association for the Study of the Liver (APASL)

Company: Trek Therapeutics (USA - MA) Theravance (Ireland)

Product: TD-6450 and faldaprevir

Action mechanism:

• direct-acting antiviral agent/NS5A inhibitor/protease inhibitor. TD-6450 is a multivalent NS5A inhibitor designed to have improved antiviral activity against genotype 1 resistance-associated variants (RAV) resistant to first generation NS5A inhibitors. TD-6450 has successfully completed Phase 1 studies in both healthy volunteers and HCV patients. Theravance Biopharma recently granted TREKtx an exclusive worldwide license for the development, manufacturing, use, marketing and sale of TD-6450 as a component in combination HCV products. Other terms of the transaction have not been disclosed. Faldaprevir is a protease inhibitor that TREKtx acquired from Boehringer Ingelheim. This compound has completed Phase 3 studies in combination with pegylated interferon and ribavirine.

Disease: hepatitis C

Therapeutic area: Infectious diseases

Country: USA

Trial details: This Phase 2a study is designed to assess the safety, efficacy, and pharmacokinetics of faldaprevir and TD-6450 in combination with ribavirin for a 12-week treatment duration in treatment-naïve participants with genotype 4 hepatitis C virus (HCV) infection. The study evaluated two doses of TD-6450, 60 mg or 120 mg QD, in combination with faldaprevir 120 mg QD and ribavirin for 12 weeks in non-cirrhotic treatment-naïve patients with chronic GT 4 HCV.(NCT02593162)

Latest news:

• • On February 13, 2017, Trek Therapeutics announced that results from an ongoing Phase 2a clinical trial to evaluate all-oral combination regimens to treat hepatitis C virus, containing faldaprevir, TD-6450, and ribavirin, will be orally presented at the Asian Pacific Association for the Study of the Liver (APASL) conference in Shanghai, China on February 15-19, 2017. The abstract entitled “Development of an Affordable and Accessible HCV Treatment: Phase 2a Study TRK-450-0201 Demonstrates Favorable Efficacy, Safety, and Pharmacokinetics of Faldaprevir+TD6450+Ribavirin in Patients with Genotype 4 HCV Infection” will be presented by Dr. Tarek I. Hassanein at Oral Presentation 18/Viral Hepatitis C - Therapeutics: New Agents 1 on Saturday, February 18 at 15:55. In this Ph2a study, 16 genotype (GT) 4 subjects without cirrhosis were randomized 1:1 in a blinded fashion and treated for 12 weeks with 60 or 120 mg TD-6450 in combination with faldaprevir 120 mg and ribavirin. SVR12 was achieved in all 16 patients, and treatment with faldaprevir, TD-6450 and ribavirin was well-tolerated. Ph2a studies evaluating the effectiveness of faldaprevir+TD6450 ± ribavirin in patients with GT1b HCV are now ongoing.   • On September 15, 2016,  Trek Therapeutics announced the first results from an open-label Phase 2a study of faldaprevir plus TD-6450 and ribavirin. The sustained viral response (SVR) rate four weeks after the completion of treatment (SVR4) was 100 percent (16 of 16) in treatment naïve patients with chronic genotype 4 (GT 4) hepatitis C virus (HCV) who received 120 mg of faldaprevir and ribavirin in combination with 60 mg or 120 mg of TD-6450 for 12 weeks. In this study, there were no serious adverse events or treatment discontinuations, and the majority of adverse events were mild. The most common adverse events observed in greater than 10 percent of patients across the study were fatigue, headache, and nausea. Efficacy results for the two arms of the study were similar. One hundred percent (100%, 16/16) of patients had HCV RNA below the lower limit of quantitation (<LLOQ, 15 IU/mL) after 3 weeks of treatment, and all 16 patients achieved SVR 4. To date, the 11 patients who have been followed for 12 weeks post-treatment have all achieved a sustained viral response (SVR12). No patients have experienced virologic breakthrough or relapse. Trek Therapeutics is currently conducting studies evaluating FDV plus TD-6450 with and without RBV in patients with GT 1b HCV in New Zealand and the United States. Phase 2b studies are planned in 2017.
• • On October 27, 2015, Theravance Biopharma and Trek Therapeutics announced that Trek Therapeutics has initiated a Phase 2a clinical trial of TD-6450, a next-generation investigational NS5A inhibitor in development to treat patients with hepatitis C virus .  The Phase 2a clinical trial will evaluate faldaprevir (FDV), an HCV protease inhibitor, combined with TD-6450 and ribavirin in patients infected with HCV genotype 4. The trial is being conducted in the United States.

Is general: Yes