Breakthrough Designation Granted to Bristol-Myers Squibb's Investigational Combination Treatment for Type-1b Chronic Hepatitis C Infection

A combination of daclatasvir and asunaprevir for type-1b hepatitis C virus infection has received breakthrough therapy designation by the FDA, meaning a faster path to approval.

The FDA has granted breakthrough therapy designation to a combination of daclatasvir (DCV) and asunaprevir (ASV) in development by Bristol-Myers Squibb (BMS). The FDA’s decision reflects positive preliminary results with the combination in patients with genotype 1b chronic hepatitis C infection (HCV).¹

To promote innovation, the breakthrough therapies designation was created on July 9, 2012, through passage of the Food and Drug Administration Safety and Innovation Act. Breakthrough therapies treat a serious or life-threatening disease, and have the support of preliminary clinical evidence indicating that the drugs may represent a meaningful improvement over currently available treatments. Drugs designated as breakthrough therapies also undergo an expedited review process.²

Although BMS announced that results of the US trial would soon be released at a scientific forum, the DCV/ASV combination has already undergone phase-3 trials in Japanese patients with genotype 1b HCV who failed to achieve cure with interferon or were intolerant to or ineligible for interferon therapy.³

Results of the study in Japan showed that the combination led to sustained viral response 24 weeks after the end of treatment (SVR24) in approximately 85% of patients with type-1b chronic HCV infection in a 222-person trial. Patients enrolled in the study were slightly older, with a higher proportion of women, than the patient populations typically treated in similar trials conducted in the United States and Europe. More than one-third of patients in the trial (40%) were older than 65 years.³

In the Japanese trial, patients ineligible for or intolerant to interferon treatment had an 87% rate of SVR24, while patients who had not responded to interferon-based treatment had a slightly lower response rate, at 81%. Patients with cirrhosis responded unusually well, with a 91% rate of SVR24, compared with an 84% response rate in patients without cirrhosis. However, it is important to note that asunaprevir does not show efficacy against genotype-2 or -3 HCV infection, and the DCV/ASV combination is less effective against type-1a HCV infection than type-1b HCV infection.³

Patients with type-1b chronic HCV infection may be interested in enrolling in a 3-year clinical trial with the DCV/ASV combination treatment from BMS. For more information on the trial, which is currently recruiting participants, please visit http://clinicaltrials.gov/ct2/show/NCT01492504.⁴

References

• Bristol-Myers Squibb receives U.S. FDA breakthrough therapy designation for all-oral daclatasvir dual investigational regimen for chronic hepatitis C. Bristol-Myers Squibb website. http://phx.corporate-ir.net/phoenix.zhtml?c=106664&p=irol-newsArticle&ID=1902689&highlight=. Accessed February 2014.
• Fact sheet: breakthrough therapies. FDA website. www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/significantamendmentstothefdcact/fdasia/ucm329491.htm. Accessed February 2014.
• AASLD 2013: daclatasvir + asunaprevir cures 85% of genotype 1b hepatitis C patients in Japanese study. HIVandHepatitis.com website. www.hivandhepatitis.com/hcv-treatment/experimental-hcv-drugs/4404-aasld-2013-daclatasvir-asunaprevir-cures-85-of-genotype-1b-hepatitis-c-patients-in-japanese-study. Accessed February 2014.
• Three-year follow-up study of subjects who participated in a previous asunaprevir (BMS-650032) and/or daclatasvir (BMS-790052) chronic hepatitis C clinical trial. ClinicalTrials.gov website. http://clinicaltrials.gov/ct2/show/NCT01492504. Accessed February 2014.