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 (DCV) 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 cirrhotic patients 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 cirrhotic patients with ribavirin (RBV) and 93% (n=53) of treatment-naïve and 87% (n=39) of treatment-experienced cirrhotic patients 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 DCV-TRIO 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