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Hepatitis C: Phase III UNITY trials results

Bristol-Myers Squibb Company has announced late-breaking data from the UNITY Trial program investigating a 12-week regimen of its all-oral daclatasvir () TRIO regimen – a fixed-dose combination of daclatasvir with asunaprevir (ASV) and beclabuvir (BCV) – in a range of patients with genotype 1 hepatitis C virus (HCV).1,2 The data was presented at The Liver Meeting® 2014. The primary endpoint for both studies was the percentage of patients who achieved cure, defined as HCV RNA less than LLOQ (25 IU/mL) TD/TND at post-treatment week 12 for treatment- naïve and treatment-experienced patients.1,2,4

The UNITY-2 study1, which evaluated in a 12-week regimen of the DCV- TRIO, showed sustained virologic response 12 weeks after treatment (SVR12) among 98% (n=54) of treatment-naïve and 93% (n=42) of treatment-experienced with ribavirin (RBV) and 93% (n=53) of treatment-naïve and 87% (n=39) of treatment-experienced without ribavirin.1

“Even with the most recent HCV treatment advances, genotype 1 patients with cirrhosis remain difficult to treat,” said Andrew J. Muir, M.D., MHS, Associate Professor of Medicine, Clinical Director, Gastroenterology & Transplant Hepatology, Duke Gastroenterology. “Currently, treatment-experienced cirrhotic patients still require a 24-week regimen to achieve high SVR rates. The data from this clinical trial using the regimen showed high cure rates for this population in a 12-week regimen, and has the potential to aid treatment adherence and provide a shorter treatment duration to achieve cure.”

Study Design and Results

The Phase III UNITY clinical trial program is an ongoing study investigating 12-week regimens of the DCV-TRIO fixed-dose combination (daclatasvir 30 mg plus asunaprevir 200mg plus beclabuvir 75 mg) in non-cirrhotic and cirrhotic genotype 1 patients.1,5

The open-label UNITY-12 study evaluated a 12-week regimen of the DCV-TRIO without ribavirin in treatment-naïve and -experienced non-cirrhotic genotype 1 patients.5 Non-cirrhotic treatment-naïve patients (n=312) and treatment-experienced patients (n=103) received the DCV- TRIO fixed-dose combination in one pill twice daily for 12 weeks, with 24 weeks of follow-up.2 The majority of the patients (73%) were genotype 1a5, and 91% of all patients achieved SVR12.2 92% of all treatment-naive patients and 89% of all treatment-experienced patients achieved cure, without the use of ribavirin.5

In the UNITY-2 study, treatment-naïve and treatment-experienced, cirrhotic genotype 1 patients received the DCV-TRIO fixed-dose combination, one arm without ribavirin (n=102) and one with ribavirin (n=100).1 The study was double-blinded to ribavirin, and the majority of the patients (74%) were genotype 1a.1 The study showed 96% of all patients who received DCV- TRIO with ribavirin achieved SVR12, and 90% of those who received DCV-TRIO without ribavirin achieved SVR12.1 “The Phase 3 UNITY results for the daclatasvir TRIO fixed-dose combination are particularly compelling for genotype 1 patients with cirrhosis, whose treatment is often harder to manage than non-cirrhotic patients,” said Douglas Manion, M.D., Head of Specialty Development, Bristol-Myers Squibb. “BMS continues to recognize that HCV is an extremely complicated disease with no ‘one-size-fits-all’ treatment solution, and the UNITY results are especially promising for serving patients with cirrhosis, a specific but significant portion of genotype 1 patients.”

In both UNITY-1 and UNITY-2 there were low rates of adverse events (AEs) leading to discontinuation and of serious adverse events (SAEs) overall.1,2 In UNITY-1 there were seven SAEs, all considered not related to study treatment, and three AEs leading to treatment discontinuation.5 The most common (>/= 10%) AEs were headache (25.8%) and fatigue (16.6%).2 In UNITY-2, there were 3 SAEs related to treatment and 4 AEs leading to discontinuation. The most common AEs were headache and fatigue (both 19.9%).4

Full abstracts for both presentations are available at The Liver Meeting website.

About Hepatitis C (HCV)

Globally, there are 150 million people infected with HCV.6 It is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products.7 Up to 90% of those infected do not spontaneously clear the virus and will become chronically infected.8 According to the World Health Organization, 20% of people with chronic HCV will develop cirrhosis and, of those, approximately 5-7% may ultimately die of the consequences of infection.9

Source

†“Cure” corresponds to an undetectable HCV RNA at 24 weeks (lower limit of detection <15 IU/ml, SVR24) which has a 99% concordance with SVR12 as the definitive cure of HCV infection – taken from EASL guidelines April 2014.

‡ One patient with HCV RNA

1 Muir A et al. All-Oral Fixed-Dose Combination Therapy With Daclatasvir/Asunaprevir/BMS-791325, ± Ribavirin, for Patients With Chronic HCV Genotype 1 Infection and Compensated Cirrhosis: UNITY-2 Phase 3 SVR12 Results. Data presentation at The Liver Meeting 2014. Abstract LB-2.

2 Bristol-Myers Squibb. AI443-102 SVR12 Topline Review: A Phase 3 Evaluation of Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination (FDC) in Non-Cirrhotic Subjects with Genotype 1 Chronic Hepatitis C. September 19, 2014.

3 Harvoni [package insert], Gilead Sciences, Inc., 2014.

4 Muir, et al. All-oral fixed-dose combination therapy with daclatasvir/asunaprevir/BMS-791325, ± ribavirin, for patients with chronic HCV genotype 1 infection and compensated cirrhosis: UNITY-2 Phase 3 SVR results. AASLD presentation, 2014.

5 Poordad, et al. All-oral, fixed-dose combination therapy with daclatasvir/asunaprevir/BMS-791325 for nin- cirrhotic patients with chronic HCV genotype 1 infection: UNITY-1 Phase 3 SVR12 results. AASLD 2014.

6 World Health Organization (WHO). “Hepatitis C Key Facts,” Available at: http://www.who.int/mediacentre/factsheets/fs164/en/ . Accessed November 2014.

7 Centers for Disease Control and Prevention. “Hepatitis C Information for the Public,” Available at: http://www.cdc.gov/hepatitis/c/ Accessed November 2013.

8 World Health Organizations (WHO). “Hepatitis C: About HCV Infection.” Available at: www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index3.html Accessed November 2014.

9 World Health Organization (WHO). “Hepatitis C.” Available at: http://www.who.int/csr/disease/hepatitis/Hepc.pdf Accessed November 2014.

Source: Bristol-Myers Squibb