Corporate news details

Bristol-Myers Squibb Company (NYSE:BMY) today announced late-breaking data from the Phase 3 ALLY-3+ trial investigating a regimen of Daklinza (daclatasvir, DCV) in combination with sofosbuvir (SOF) and ribavirin (RBV) in genotype 3 hepatitis C (HCV) patients with advanced fibrosis or cirrhosis, for treatment durations of 12 and 16 weeks. This patient population is one of the most difficult to treat, among whom sustained virologic response (SVR) rates, or cure, have proved harder to achieve.

The results show that 100% of patients in the advanced fibrosis (F3) cohort achieved SVR12 in both the 12- and 16-week arms of the study. SVR12 rates were 83% and 89% in patients with cirrhosis in the 12- and 16-week arms, respectively. Results will be presented today at The Liver Meeting^® 2015, the annual meeting of The American Association for the Study of Liver Diseases (AASLD), in San Francisco, CA, November 13 – 17.

Daklinza is an NS5A replication complex inhibitor approved by the U.S. Food and Drug Administration (FDA) for use with sofosbuvir for the treatment of adults with HCV genotype 3. Sustained virologic response (SVR) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving Daklinza in combination with sofosbuvir for 12 weeks. Daklinza is contraindicated in combination with medicinal products that strongly induce CYP3A and P-glycoprotein transporter, as this may lead to lower exposure and loss of efficacy of Daklinza. Daklinza must not be administered as a monotherapy.

“High cure rates for patients with genotype 3 with advanced fibrosis or cirrhosis have remained elusive, so we are encouraged by these results,” said Dr. Alex Thompson, Professor, St. Vincent's Hospital and the University of Melbourne, Australia. “Our hope with the ALLY-3+ trial was to study this investigational regimen in the most difficult-to-cure genotype 3 patients, and to improve cure rates for this patient population.”

In the ALLY-3+ study, the daclatasvir+sofosbuvir+ribavirin combination regimen had no discontinuations due to adverse events (AEs) or treatment-related serious AEs. The most frequent AEs were insomnia (30%), fatigue (26%) and headache (24%). Additionally, relapse occurred in four patients (two in the 16-week and two in the 12-week arm). There was one death (12-week arm; not treatment-related). There were no virologic breakthroughs.

“Our continued scientific exploration of the potential for Daklinza used in combination with other direct-acting antivirals for HCV patients has yielded these encouraging results,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “We remain committed to delivering therapeutic options to HCV patients with unmet needs around the globe, including those with more complicated disease and other difficult-to-treat groups such as genotype 3 patients with more advanced liver disease who still need help to achieve cure.”

ALLY-3+ Study Design

This open-label, Phase 3b study in HCV genotype 3-infected treatment-naive or -experienced patients with advanced fibrosis or compensated cirrhosis randomized patients 1:1 to receive 12 weeks versus 16 weeks of Daklinza (60 mg QD) + SOF (400 mg QD) + RBV (weight-based), stratified by advanced fibrosis or cirrhosis status.

Fifty patients were treated (12 weeks: 24 patients; 16 weeks: 26 patients). The majority of patients were male (80%), white (98%), and treatment-experienced (74%; 10% prior relapse on SOF+RBV); 72% had cirrhosis and 52% had HCV RNA ≥6 million IU/mL. Baseline characteristics were comparable between arms.

The primary endpoint was to estimate SVR12 in treatment-naive or -experienced subjects with compensated advanced fibrosis/cirrhosis (F3-F4) treated for 12 weeks and for 16 weeks.

The full abstract for the presentation, containing the SVR4 data, is available at The Liver Meeting website.

About Genotype 3

Affecting an estimated 54.3 million people (30% of all HCV patients) worldwide, genotype 3 is the second most common HCV genotype globally and is considered one of the most difficult to treat. The more aggressive nature of genotype 3 lies in the damage it causes to the liver, as it is associated with accelerated fibrosis progression. Recent research has also shown the risk of cirrhosis for patients infected with HCV genotype 3 is 31% greater than for those with HCV genotype 1.

About Bristol-Myers Squibb in HCV

Bristol-Myers Squibb is focused on helping to eradicate hepatitis C around the world, with a primary emphasis on difficult-to-treat patients, including those millions in countries such as China where population-based HCV solutions remain a high unmet need. Among the company’s data being presented at AASLD this year is the first all-oral, DAA Phase 3 trial in HCV completed in China.

In July 2014, Japan became the first country in the world to approve the use of a daclatasvir-based regimen for the treatment of chronic hepatitis C. Since then, daclatasvir-based regimens have been approved in more than 50 countries across Europe, Central and South America, the Middle East and the Asia-Pacific region.

Indication and Important Safety Information - DAKLINZA™ (daclatasvir)

INDICATION

DAKLINZA™ (daclatasvir) is indicated for use with sofosbuvir for the treatment of adults with genotype 3 chronic hepatitis C virus (HCV) infection.

Limitations of Use:

• Sustained virologic response (SVR) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving DAKLINZA in combination with sofosbuvir for 12 weeks.

IMPORTANT SAFETY INFORMATION

• Drugs Contraindicated with DAKLINZA: strong inducers of CYP3A that may lead to loss of efficacy of DAKLINZA include, but are not limited to:
  • Phenytoin, carbamazepine, rifampin, St. John’s wort (Hypericum perforatum)

WARNINGS and PRECAUTIONS

• Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: Coadministration of DAKLINZA and other drugs may result in known or potentially significant drug interactions. Interactions may include the loss of therapeutic effect of DAKLINZA and possible development of resistance, dosage adjustments for other agents or DAKLINZA, possible clinically significant adverse events from greater exposure for the other agents or DAKLINZA.

• Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone: Post-marketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another direct-acting antiviral, including DAKLINZA. A fatal cardiac arrest was reported with ledispasvir/sofosbuvir.
  • Coadministration of amiodarone with DAKLINZA in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options, patients should undergo cardiac monitoring, as outlined in Section 5.2 of the prescribing information.
  • Bradycardia generally resolved after discontinuation of HCV treatment.

Adverse Reactions

• The most common adverse reactions were (≥ 5%): headache (14%), fatigue (14%), and nausea (8%), diarrhea (5%).

Drug Interactions

• CYP3A: DAKLINZA is a substrate. Moderate or strong inducers may decrease plasma levels and effect of DAKLINZA. Strong inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir) may increase plasma levels of DAKLINZA.
• P-gp, OATP 1B1 and 1B3, and BCRP: DAKLINZA is an inhibitor, and may increase exposure to substrates, potentially increasing or prolonging their adverse effect.

See Section 7 of the Full Prescribing Information for additional established and other potentially significant drug interactions and related dose modification recommendations.

Daklinza in Pregnancy: No data with Daklinza in pregnant women are available to inform a drug-associated risk. Animal studies of Daklinza at exposure above the recommended human dose have shown maternal and embryofetal toxicity. Consider the benefits and risks of Daklinza when prescribing Daklinza to a pregnant woman.

Nursing Mothers: Daklinza was excreted into the milk of lactating rats; it is not known if Daklinza is excreted into human milk. Consider the benefits and risks to the mother and infant when breastfeeding.

Please click here for the DAKLINZA full prescribing information

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that Daklinza will be approved for the additional indication mentioned above. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2014 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.