Bristol-Myers Squibb receives CFDA approval for all-oral regimen for HCV Daklinza in combo with Sunvepra

• This is China’s first all-oral, interferon- and ribavirin-free HCV treatment regimen.  In addition, Daklinza has been approved in China for combination use with other agents, including sofosbuvir, for adult patients with HCV genotypes 1-6 infection. This is the only all-oral pan-genotypic regimen recommended by China’s HCV Prevention and Treatment Guideline. Daklinza must not be administered as monotherapy. Sofosbuvir is under review by the CFDA, and is not currently licensed in China.
• In more than 60 countries, Daklinza is approved as part of a regimen with either Sunvepra or sofosbuvir. In China, Daklinza-based regimens provide a shorter treatment duration (12 or 24 weeks) compared to 48 weeks of treatment with previously approved regimens. The Daklinza and Sunvepra regimen is already approved by regulatory authorities in multiple countries across the Asia Pacific, Latin America, and Eastern Europe regions. Sunvepra is not approved in the United States.
• “The burden of HCV in China is extremely high, and now for the first time, we have an all-oral treatment option in the combination of Daklinza and Sunvepra, which is a significant step forward for patients and doctors alike,” said Hui Zhuang, a professor at the Beijing University Medical School and a member of the Chinese Academy of Engineering. “This new option helps to address many of the unmet needs for our HCV genotype 1b patients, and is also included in the latest edition of China’s HCV Prevention and Treatment Guideline.”
• The approval is based primarily upon results of the first completed phase 3 036 trial of the Daklinza and Sunvepra regimen for HCV among Chinese patients, which was published in the November 2016 issue of the Journal of Gastroenterology and Hepatology. In the trial, 91% (145/159) of genotype 1b patients who had been previously interferon-ineligible or interferon-intolerant achieved sustained virologic response (“SVR”, or cure) at post-treatment week 24. The cure rate was higher, at 99%, in patients without baseline NS5A resistance-associated variants (RAVs; L31M or Y93H; n=137/139).
• As detailed in the published phase 3 trial, one death (0.6%), five on-treatment serious adverse events (3%), and three grade 4 laboratory abnormalities (2%) occurred on-treatment; none were considered related to study drugs. Two patients (1%) discontinued due to adverse events (AEs). The most common grade 1–4 on-treatment AEs (>5% of patients) were platelet count decrease (14, 9%), upper respiratory tract infection (13, 8%), ALT increase (a diagnostic indication of liver disease or damage) (11, 7%), neutrophil count decrease (11, 7%), monocyte (large white blood cell) count decrease (10, 6%), white blood cell count decrease (10, 6%), thrombocytopenia (decrease in the number of platelets in the blood) (10, 6%), and pruritus (itchiness) (9, 6%); most were mild or moderate in intensity. Treatment was generally well-tolerated regardless of cirrhosis status.
• “We are proud to build on our legacy, infrastructure and experience in treating viral hepatitis throughout Asia by bringing Daklinza-based regimens to patients in China,” said Murdo Gordon, executive vice president and chief commercial officer, Bristol-Myers Squibb. “Beginning with our efforts to treat chronic hepatitis B, Bristol-Myers Squibb has been committed to combating viral hepatitis in China for over a decade.”
• HCV represents a significant public health burden in China and is now the fourth most commonly reported infectious disease countrywide, with an estimated 10 million people currently living with the disease. Until now, standard of care in China has been interferon- and ribavirin-containing regimens which have left some patient groups with unmet needs. The cure rate for interferon- and ribavirin- containing regimens varies in a number of recent Chinese studies. In CCgenos, a real-world observation study, the cure rate for interferon- and ribavirin- containing regimens among GT-1b naïve patients is 62.4%.
• Karl Lintel, MD, president of Bristol-Myers Squibb (China) Investment Co. Ltd and the Sino-American Shanghai Squibb Pharmaceutical Co., commented, “Today’s approval of Daklinza and Sunvepra is great news for patients in China, as we continue the global fight against chronic hepatitis C. This milestone is testament to our ongoing collaboration with multiple stakeholders, and aligning with government policies to provide continuing support to HCV patients at the community level.
• Daclatasvir, marketed as Daklinza, is a NS5A replication complex inhibitor which targets the NS5A protein by directly disrupting its normal function. The NS5A protein plays essential roles in the HCV viral life cycle, including viral RNA replication and virion (viral particle) assembly. Daklinza is approved by the U.S. Food and Drug Administration (FDA) for use with sofosbuvir, with or without ribavirin, for the treatment of patients with HCV genotype 1 or genotype 3 infection. Sustained virologic response (SVR12) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving Daklinza in combination with sofosbuvir for 12 weeks. Daklinza is approved by the European Medicines Agency (EMA) for patients with HCV genotypes 1, 3, or 4.
• Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with Daklinza. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate management for HBV infection as clinically indicated. 
• Asunaprevir, marketed as Sunvepra, is an NS3 protease inhibitor, an agent that binds to the NS3 protein of the HCV virus to block its activity. The NS3/4A protease plays an essential role in the assembly of the viral replication complex. Sunvepra is approved in 17 countries around the world, including in the Asia Pacific, Latin America, and Eastern Europe regions; Sunvepra is not approved in the United States. Sunvepra is approved as part of a regimen with Daklinza for the treatment of HCV genotype 1b infection in adult patients. For patients receiving Sunvepra-containing regimens, frequent monitoring of liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and bilirubin is required until completion of therapy

Bristol-myers squibb receives cfda, hcv daklinza