Recent actions by the FDA to accelerate simeprevir’s journey to market may be instrumental in helping close the treatment gap for genotype 1 hepatitis C patients in need.


The hepatitis C (HCV) patient population is incredibly complex and diverse. Patients with genotype 1 chronic HCV—especially patients who have relapsed after prior interferon-based treatment—can be particularly difficult to cure.
 
The current standard of care for genotype 1 chronic HCV involves treatment with pegylated interferon and ribavirin plus a protease inhibitor, but a number of new agents in the pipeline have been creating a great deal of buzz in the HCV community. In fact, many physicians are encouraging their HCV patients to defer treatment (a practice known as “warehousing”) until these new, potentially more effective drugs are approved by the FDA.
 
These investigational agents reportedly have fewer side effects than the interferon-based therapies and appear to produce significantly higher sustained virologic response (SVR) rates in clinical trials. In addition, most of the new therapies can be taken orally. Before 2011, all HCV treatments required weekly injections.
 
If these new interferon-free medications are approved, their impact could be widespread. Indeed, uptake of the new therapies is expected to quadruple spending on HCV over the next 3 years, according to a recent drug trend forecast from Express Scripts.
 
Simeprevir, a protease inhibitor developed by Janssen and Medivir, is 1 of the prospective agents that has been creating a stir in the HCV community. The FDA recently granted the drug priority review, which may accelerate its journey to market and help close the treatment gap for patients in need. Janssen is seeking approval for simeprevir administered once daily along with pegylated interferon and ribavirin to treat adult patients with genotype 1 chronic HCV with compensated liver disease.
 
Janssen’s HCV clinical development program has investigated simeprevir’s potential use in a number of different treatment combinations and HCV patient populations. Specialty Pharmacy Times recently corresponded with Gaston Picchio, hepatitis disease area leader at Janssen, to learn more about the development of simeprevir.
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SPT: What is novel about simeprevir?

GP: Currently available protease inhibitors are administered 3 times daily in the United States and 2 or 3 times daily in the European Union. If simeprevir is approved by the FDA, it would offer the option of a protease inhibitor–based regimen that includes simeprevir taken once daily for 12 weeks in combination with 24 or 48 weeks of pegylated interferon and ribavirin.

SPT: How does simeprevir compare with other protease inhibitors already on the market in terms of sustained virologic response?

GP: Simeprevir has not been investigated in a head-to-head study with other PIs already on the market. 

In the QUEST-1 and QUEST-2 Phase 3 trials, the use of simeprevir led to sustained virologic response 12 weeks after the end of treatment (SVR12) in 80% and 81%, respectively, of treatment-naïve genotype 1 chronic hepatitis C adult patients with compensated liver disease, including all stages of liver fibrosis, when administered once daily with pegylated interferon and ribavirin. In the PROMISE Phase 3 trial, the use of simeprevir led to SVR12 in 79% of treatment-experienced genotype 1 chronic hepatitis C adult patients with compensated liver disease, including all stages of liver fibrosis, when administered once daily with pegylated interferon and ribavirin.

SPT: What is the anticipated FDA approval date for simeprevir? Will the drug’s Priority Review status affect this date?

GP: On March 28, 2013, Janssen announced it had submitted a New Drug Application (NDA) to FDA seeking approval for simeprevir with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C in adult patients. In May, the FDA granted Priority Review to the NDA for simeprevir.  

Under the Prescription Drug User Fee Act, FDA review will begin approximately 60 days after receipt of the application and will aim to be complete within 6 months from when the review period begins, which for simeprevir is expected to be in late November. 

SPT: Tell us something about the drug that may not have been included in the press releases from Janssen that you think is important to note.

GP: Simeprevir is being studied in combination with several direct-acting antiviral agents with different mechanisms of action, with and without ribavirin, as part of multiple interferon-free regimens. These include:

1. The Phase 2 COSMOS study of simeprevir and Gilead’s nucleotide inhibitor sofosbuvir (GS-7977) in treatment-naïve and previous null-responder genotype 1 HCV patients, including patients with cirrhosis;
2. A Phase 2 study of simeprevir and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir in treatment-naïve and previous null-responder genotype 1 HCV patients; and
3. A Phase 2a trial of simeprevir and TMC647055, Janssen R&D Ireland’s non-nucleoside polymerase inhibitor, with and without ribavirin in treatment-naïve genotype 1a and 1b HCV patients.

SPT: Were pegylated interferon and ribavirin added to therapy in both of the QUEST trials and the PROMISE trial?

GP: In QUEST-1, QUEST-2, and PROMISE, patients were randomized to receive one 150 mg capsule of simeprevir or placebo once daily plus pegylated interferon and ribavirin for 12 weeks, followed by pegylated interferon and ribavirin alone for either 12 or 36 weeks based on response-guided therapy.  

SPT: NDAs were submitted in both United States and Japan for simeprevir. What factors went into filing in these 2 areas in particular?

GP: In February, Janssen submitted a regulatory application to Japanese authorities for approval of simeprevir administered with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C patients who are treatment-naïve, prior non-responders, or relapsed following treatment with pegylated interferon with or without ribavirin. This was the first worldwide regulatory application for simeprevir.

In March, Janssen submitted a New Drug Application to the FDA seeking approval of simeprevir administered once daily with pegylated interferon and ribavirin for the treatment of adult patients with genotype 1 chronic HCV with compensated liver disease.

Additionally, in April, Janssen submitted a Marketing Authorisation Application to the European Medicines Agency seeking approval for simeprevir administered as 1 capsule once daily with pegylated interferon and ribavirin for the treatment of genotype 1 or genotype 4 chronic hepatitis C in adult patients with compensated liver disease (including cirrhosis), with or without HIV-1 co-infection, who are treatment-naïve or who have failed previous interferon-based therapy.

SPT: It has been said that simeprevir treatment will be part of an “interferon-free regimen.” Could you please explain what this means and the benefit of not using an interferon regimen to treat HCV?

GP: As a result of the complexity and diversity of the patient population, a proportion of patients with HCV do not tolerate interferon-containing regimens. Therefore, physicians need multiple treatment options, including interferon-free ones, in order to provide their patients the best possible chance at successful therapy.