HCV Therapies Ready to Tip

For an infectious disease that effects over 7 million people in the United States and Europe alone, treatments for the hepatitis C virus (HCV) have been relatively scant. However, a current race to market between Merck and Vertex/ Tibotec/Mitsubishi Tanabe Pharma could be the tipping point for HCV therapies for the next five to 10 years.

Within a one-week period, both Merck and Vertex announced its respective investigational treatments— boceprevir and telapriver—had positive Phase III results and both companies were preparing to submit their NDAs this year. Merck is planning a rolling submission to the FDA, with completions to FDA and in the EU this year. Vertex indicated in a press release its submission would go to the FDA in the fourth quarter.

The current standard of care, which is about 10 years old, is a 48 to 72 weeks of treatment with pegylated interferon and ribavirin. There is a high side effect profile associated with this standard, a failure to respond to the therapy, as well as the negative aspect of receiving the drug combination via injection.

Both boceprevir and telapriver are protease inhibitors, and delivered via capsule and tablet respectively. The side effects for the 48-week treatment group of boceprevir were fatigue, headache, nausea, anemia, and bad taste. For telaprevir, the side effects were similar: fatigue, itching, nausea, anemia, rash, and headache. However, Vertex believes it has the edge with a lower rate of anemia. In either case, if the drugs are approved, analysts believe the current $2 billion market could grow to $10 billion in five years.

While Merck and Vertex stand to gain much from beating the pack to the approval finish line, other companies have either lost out or are fast progressing to provide therapies to the underserved and underdiagnosed population.

On the heels of the mid-August Vertex announcement, Pharmasset announced it had received fast track designation from FDA for its oral treatment of chronic HCV infection. Pharmasset expects to initiate a 12-week Phase IIb study of its PSI-7977 in the fourth quarter of 2010. PSI-7977 is a uridine nucleotide analog polymerase inhibitor of HCV. On the opposite end, in June, Human Genome Sciences (HGS) received preliminary feedback from the FDA on its BLA for its albinterferon alfa-2b treatment for HCV. The FDA expressed concern over the risk benefit assessment on the dosing. Novartis had licensing agreements with HGS, and had withdrawn its application to the EMA for the same treatment in April. HGS and Novartis are reportedly in talks toward developing another dosing regimen for the drug.

Other targets for HCV are vaccines. The PhRMA database lists six vaccines in development for HCV.

For clinical trials professionals, designing and managing HCV trials, as most therapeutic areas, has unique challenges. For example, the Merck HCV SPRINT-2 study for boceprevir enrolled 1097 treatment-naïve subjects at U.S. and international sites into two separate cohorts, one with 938 non-African-American/Black subjects and the other with 159 African-American/Black subjects. The results were analyzed separately based on the fact that several previous studies have shown that African-American/Black patients have a lower response to HCV treatment than non-African-American/Black patients. In this study, non- African-American/Black subjects had a 69 percent sustained virological response, the African-American/Black subjects a 53 percent response.

HCV subjects for trials

Another challenge of HCV trials is subject recruitment. Praxis, a centralized recruitment services company, recently announced it had successfully completed a second recruitment program for an unnamed sponsor in a HCV study. The Praxis campaign built upon the brand identity established in its first campaign, to enable it to enroll the 150 percent more subjects needed from the previous study. One achievement from the first campaign was success with online strategies. The second campaign featured a combination of Web advertising, social media, and newspaper advertising leading interested parties to a Praxis-maintained study Web site. Sixty percent of all sites participated in the Praxis campaign; with those sites contributing 84 percent of all randomized subjects.

According to Chris Layfield, Director of Marketing for Brentwood, TN-based Praxis, the company looked closely at the demographic profile of a patient most likely to qualify for the study by analyzing research, industry data, and previous Praxis study metrics. “Individuals with a lower socioeconomic status have an increased likelihood of contracting HCV, so reaching these individuals was important to the overall success of the recruitment program,” Layfield told Applied Clinical Trials. “It was also important that our communications spoke to key influencers since the HCV treatment process requires a significant commitment from both family and friends. We needed to craft a plan that successfully got study materials and information into the hands of these individuals.”

And while lower socioeconomic groups would lend to a belief that Internet is not an option, Layfield noted that many cities in the United States offer free Internet access to public libraries, community centers, and homeless shelters, which aided in the successful enrollment of the program.