Bristol-Myers Reports Positive Data From HCV Regimen Phase 3 Trial

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The FINANCIAL — Bristol-Myers Squibb Company on February 22 announced data from the first completed all-oral chronic hepatitis C (HCV) regimen Phase 3 trial that includes a Chinese patient population.

The results of the registrational trial, which studied daclatasvir in combination with asunaprevir for 24 weeks in Asian (non-Japanese) patients with genotype 1b HCV, were presented today at the Asian Pacific Association for the Study of the Liver Conference (APASL) in Tokyo. Genotype 1b is particularly prevalent in China, where interferon/ribavirin combination regimens are still the current standard of care, according to Bristol-Myers Squibb.

The primary endpoint of the study was sustained virologic response at post-treatment week 24 (SVR24). In the study, 91% of patients from China achieved SVR24, which rose to 98% of patients without NS5A resistance-associated variants (RAVs) at baseline. SVR24 results were similarly high across all subgroups with genotype 1b HCV, including those with cirrhosis (90%), and patients from Korea (94%) and Taiwan (87%).

SVR24 rates were also higher in all patients without baseline NS5A RAVs (n=137/139 [99%]), regardless of the presence (98%) or absence (99%) of cirrhosis, and lower in patients with baseline NS5A RAVs (n=8/19 [42%]). Baseline NS5A RAVs were present in 12% of patients. HCV NS5A RAVs exist naturally (albeit in lower prevalence vs wildtype) and can emerge after virologic response failure. Screening for the presence of specific NS5A mutations can help physicians determine the best patients for treatment by identifying those most likely to achieve cure with an NS5A-containing regimen.

In the trial presented today, across all patient cohorts, all serious adverse events (SAEs) (n=5/159 [3%]), grade 4 laboratory abnormalities (n=3/159 [1.9%]) and deaths (n=1/159 [1%]) that occurred on treatment were unrelated to the study drugs. Two patients discontinued due to adverse events (AEs). The most common AEs (> 5% of patients) were decrease in platelets (9%), upper respiratory tract infection (8%), ALT increase (7%), ANC decrease (7%), monocyte decrease (6%), white blood cell decrease (6%), thrombocytopenia (6%), and pruritus (6%).

“These results signal that the daclatasvir and asunaprevir regimen could provide a highly effective all-oral, interferon- and ribavirin-free treatment for many Chinese HCV patients with genotype 1b infection,” said Dr. Lai Wei, Professor of Hepatology & Medicine and Director, Peking University Hepatology Institute, Chief, Department of Hepatology, Peking University People’s Hospital. “This is an important finding because the burden of HCV in China is extremely high, and newer direct-acting antivirals have yet to be introduced for any patients.”

The daclatasvir and asunaprevir regimen already is approved by regulatory authorities in several countries across the Asia Pacific region, including Japan, Korea and Taiwan, as well as in some countries in Latin America and Eastern Europe. At APASL, Bristol-Myers Squibb is also presenting other data for the daclatasvir and asunaprevir regimen in Asian populations, including integrated safety, pooled resistance and pooled exposure data.

“So much progress has been made globally in the fight against chronic hepatitis C, but the battle against the disease is not over,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “At Bristol-Myers Squibb, we continue to seek out areas and patient populations that remain in need of new treatment solutions, such as China, where at last count 13 million people are estimated to be living with the disease.”

Study Design

The Phase 3, open-label study evaluated daclatasvir and asunaprevir in interferon- ineligible and/or intolerant non-Japanese Asian patients with chronic HCV genotype 1b infection. Patients received daclatasvir 60 mg (tablet) once daily plus asunaprevir 100 mg (soft capsule) twice daily for 24 weeks. The primary endpoint was sustained virologic response at post-treatment week 24 (SVR24). The study treated 159 patients overall, 80% from mainland China, 11% from Korea and 9% from Taiwan, including patients with cirrhosis (33%), IL28B nonCC genotypes (40%), and aged ≥70 years (4%). 


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