Back HCV Treatment Interferon-free HCV Treatment: Simeprevir and ALS-2200 Enter Phase 2 All-oral Studies

Interferon-free HCV Treatment: Simeprevir and ALS-2200 Enter Phase 2 All-oral Studies


A trio of interferon-free, all-oral regimens for treatment of chronic hepatitis C virus (HCV) are entering Phase 2 clinical trials, the intermediate stage of development after basic safety and antiviral activity have been established, according to recent press releases from Medivir and Vertex.

Simeprevir + TMC647055

Stockholm-based Medivir announced last week that it will soon start a Phase 2a study looking at a dual oral regimen of the HCV NS3/4A protease inhibitorsimeprevir (formerly TMC435) plus the non-nucleoside HCV NS5B polymerase inhibitor TMC647055.

Medivir is jointly developing simeprevir with Janssen, which includes the former Tibotec Therapeutics. The once-daily protease inhibitor produced impressive cure rates in combination with pegylated interferon/ribavirin and is now in Phase 3 studies.

This open-label Phase 2 study will enroll approximately 40 chronic hepatitis C patients with HCV genotype 1. The study will be divided into 2 parts; the first will include genotype 1a or 1b treatment-naive patients and people who relapsed after treatment with pegylated interferon/ribavirin, while the second will enroll difficult-to-treat genotype 1a prior null responders.

Participants will receive simeprevir, TMC647055, and low-dose ritonavir as a booster, with or without ribavirin for 12 weeks. The primary endpoint will be SVR12, or sustained virological response 12 weeks after the end of treatment.

"This study is in line with Medivir's and Janssen's strategy to evaluate different combination possibilities with simeprevir for interferon-free HCV treatments," said Charlotte Edenius, Medivir EVP of Research and Development. "This will broaden our understanding of simeprevir, which we believe has the necessary characteristics to potentially become a key component of future hepatitis C treatment regimens, including combination with interferon and ribavirin as well as interferon-free therapies."

ALS-2200 + Ribavirin or Telaprevir

Vertex Pharmaceuticals and its collaborator Alios BioPharma recently released new data from an ongoing viral kinetic study testing the uridine nucleotide analog polymerase inhibitor pro-drug ALS-2200 (also known as VX-135).

In a cohort of 8 treatment-naive genotype 1 chronic hepatitis C patients, HCV viral load fell by a median 4.18 log after 7 days of treatment with 200 mg once-daily ALS-2200 plus ribavirin. Within this group, 5 participants achieved HCV RNA levels below the limit of quantification (< 25 IU/mL) and 2 had levels below the limit of detection. ALS-2200 was well-tolerated overall, with no serious adverse events and no study participants discontining treatment due to side effects.

"Our goal is to develop all-oral regimens that are well-tolerated and provide a high rate of viral cure in a broad population of people with chronic hepatitis C," said Robert Kauffman, Vertex senior vice president and chief medical officer. "We're making good progress and expect to begin all-oral Phase 2 combination studies by the end of this year."

Vertex is planning a pair of Phase 2 trials looking at ALS-2200 in combination with either ribavirin or the company's approved HCV protease inhibitor telaprevir (Incivek) for genotype 1 chronic hepatitis C patients. The studies will evaluate 12 weeks of treatment with a primary endpoint of SVR12.

Vertex also announced last week that it is halting development of the adenosine nucleotide analog polymerase inhibitor pro-drug ALS-2158 due to lack of efficacy. A study of genotype 1 chronic hepatitis C patients found that doses of up to 900 mg ALS-2158 for 7 days were well-tolerated, but "there was insufficient antiviral activity to warrant proceeding with further clinical development."



Medivir AB. A Phase IIa Interferon Free Combination Hepatitis C Trial of Simeprevir (TMC435) and TMC 647055 Will Commence Shortly. Press release.  September 20, 2012.

Vertex Pharmaceuticals. Vertex Announces New Data on ALS-2200 in People With Hepatitis C, Supporting Advancement into Phase 2 All-Oral Studies in 2012; Ends Development of ALS-2158. Press release. September 25, 2012.