Activists are decrying Gilead's refusal to continue codeveloping a winning HCV drug combination with Bristol-Myers Squibb (BMS), opting instead to focus on co-formulations of its own promising agents. While a high-level petition continues to circulate, demanding that Gilead continue codevelopment with BMS, a much larger advocacy agenda remains to be addressed.
The imbroglio began with the completion of a phase IIa study involving Pharmasset's nucleotide polymerase inhibitor sofosbuvir (PSI-7977) and BMS's NS5A inhibitor daclatasvir. In the absence of pegylated interferon and ribavirin, cure rates were an astonishing 100 percent after 12 or 24 weeks of treatment for people with HCV genotype 1, and between 88 and 100 percent of people with HCV genotypes 2 and 3.
Meanwhile, Gilead purchased Pharmasset for almost $11 billion in January 2012. But instead of advancing the sofosbuvir/daclatasvir regimen into phase III studies, Gilead abandoned daclatasvir in favor of developing a fixed-dose combination (FDC) with its own NS5A inhibitor, ledipasvir (GS-5885).
Gilead's FDC performed well in a phase II trial -- 100 percent of 25 previously untreated people and 9 null responders maintained undetectable HCV after 12 weeks of treatment -- but ribavirin was included in the mix. Whether Gilead's FDC works this well without ribavirin is currently being explored in phase III studies.
Gilead's decision -- should it also abandon another promising collaboration with Janssen Therapeutics, community opinion may be further soured -- makes the company a tempting (and deserving) target.
A petition demanding President Obama broker ongoing collaboration between Gilead and BMS has found a wide audience. But a campaign against Gilead should broaden the focus from pre-approval trials to providing real-world access, by tackling these issues:
Pricing. Charging exorbitant prices for lifesaving drugs will limit access far more than a company's refusal to continue a codevelopment plan. By the end of 2013, sofosbuvir, daclatasvir, and Janssen's protease inhibitor simeprevir are likely to be approved -- all expected to be the costliest HCV drugs to date. It is likely that that these drugs will be combined. But payers may balk, in the absence of phase III trials confirming their combined efficacy, and refuse reimbursement. Advocacy efforts to identify and target public and private insurance companies who refuse to cover these combos are likely to save more lives than demanding a pre-approval trial.
Early access. Some people cannot wait until approval -- they need HCV treatment now. TAG has been advocating with allies in the U.S. and Europe for trials involving people with advanced liver disease who are ineligible for studies currently required by regulatory agencies. These "early access" trials may be lifesaving, and will provide critical information on safety and efficacy in people who need treatment most.
Inclusive trials. Gilead is moving its FDC to market as quickly as possible. There is no information on safety, efficacy, and tolerability of sofosbuvir plus an NS5A inhibitor in people with HIV/HCV coinfection, cirrhosis, or renal impairment -- but these are the people most likely to use the FDC. It is to Gilead's advantage to support trials in these populations with the FDC and sofosbuvir-based combinations with drugs from other companies.