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Two HCV Treatments Lose Breakthrough Therapy Designation
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According to two manufacturers, the FDA is taking the new landscape of hepatitis C virus treatments into consideration and removing the designation of breakthrough therapy for two different regimens.
The FDA has rescinded breakthrough therapy designation status from Bristol-Myers Squibb for daclatasvir for the treatment of hepatitis C virus infection, according to a statement from Bristol-Myers Squibb, and there are plans to retract the same status for the combination regimen of grazoprevir and elbasvir, according to 2014 financial results released by Merck.
Evolving HCV Landscape
“The FDA has informed Bristol-Myers Squibb that, due to the evolving HCV treatment landscape, the agency intends to rescind the breakthrough therapy designation for certain genotype 1 hepatitis C regimens related to daclatasvir,” the statement from Bristol-Myers Squibb said. “This will not impact our current submission/resubmission timetable of the new drug application for daclatasvir in combination with other antiviral agents for the treatment of hepatitis C.”
According to the financial report available on the Merck website, Merck received notification from the FDA on Jan. 30 of its intent to revoke the breakthrough designation status of grazoprevir and elbasvir (MK-5172, MK-8742; Merck) due to other recently approved treatments for HCV genotype 1 patients.
Merck spokesperson Sarra S. Herzog confirmed via email that Merck was notified of the FDA’s request to rescind the designation, but noted that the FDA has not done so yet.
“The U.S. FDA informed us of their intention to rescind our breakthrough designation for grazoprevir/elbasvir for the treatment of genotype 1 HCV infection,” Herzog told Healio Gastroenterology. “Note that they have not yet rescinded [breakthrough therapy designation].”
Daclatasvir
Daclatasvir (Bristol-Myers Squibb) was granted breakthrough therapy designation in early 2014 as part of a dual investigational regimen with asunaprevir (Bristol-Myers Squibb) for chronic HCV. Bristol-Myers Squibb withdrew its application for asunaprevir from the FDA in October 2014.
In November, the FDA submitted a letter to BMS requesting more information on daclatasvir.
“Bristol-Myers Squibb is dedicated to the ongoing clinical development program for daclatasvir, a potent, pan-genotypic NS5A complex inhibitor (in vitro), which is currently being investigated globally in multiple treatment regimens for HCV patients with high unmet need,” according to the statement. “The company continues to progress its daclatasvir clinical trial program focused on patients with high unmet needs, including pre- and post-liver transplant (ALLY-1), HCV patients co-infected with HIV (ALLY-2) and patients with genotype 3 (ALLY-3). Our regulatory filing strategy is developed on a country-by-country basis, and we decide on filings in specific countries based upon the epidemiological needs of the patients living there, as well as the competitive landscape.”
ALLY-3 results presented at the 2014 Liver Meeting showed daclatasvir in combination with sofosbuvir (Sovaldi, Gilead Sciences) but without ribavirin produced 90% sustained virologic response at 12 weeks in a treatment-naive group and an 86% SVR12 in the treatment-experienced group. Results were not as impressive in patients with cirrhosis. ALLY-2 results were presented at CROI 2015, showing a 97% SVR12 in patients coinfected with HIV and HCV.
Grazoprevir/Elbasvir
Merck still plans on filing a new drug application with the FDA in the upcoming months for the combination of grazoprevir and elbasvir, according to the financial report.
Herzog added: The FDA has indicated its determination is based on the availability of newly registered drugs that address this medical need. The company expects to discuss this matter with the FDA and does not expect that it will impact its ability to file [a new drug application] for this combination regimen or the timing of that filing.”
Herzog also stated that Merck will be meeting with the FDA.
“During this meeting, Merck will have the opportunity to provide additional information which will help the agency determine the criteria for [breakthrough therapy designation] to continue to be met,” Herzog said.
Stephanie Yao from the Office of Media Affairs for the FDA declined to comment on the matter saying the FDA is unable to do so due to “federal law and FDA regulations [prohibiting] the agency from discussing products undergoing development.”
At the 2014 Liver Meeting in Boston, phase 2 study results were presented that indicated the treatment regimen was safe and well tolerated among treatment-naive patients with HCV genotype 1 and cirrhosis and patients previously treated with pegylated interferon and ribavirin, with or without cirrhosis, after 12 or 18 weeks of therapy.
Merck first received breakthrough therapy designation for the combination regimen in October 2013, according to Herzog. – by Melinda Stevens
Disclosures: Herzog is an employee of Merck. Yao reports no relevant financial disclosures.