European Regulators Give Positive Opinion on Daclatasvir for Hepatitis C

Bristol-Myers Squibb announced this week that the European Medicines Agency's Committee for Medicinal Products for Human Use has recommended approval of its hepatitis C virus (HCV) NS5A inhibitor daclatasvir, which has been given the brand name Daklinza.

Daclatasvir has performed well in clinical trials of interferon-free regimens with other direct-acting antivirals including BMS's HCV protease inhibitor asunaprevir, Janssen's protease inhibitor simeprevir (Olysio), and Gilead Science's nucleotide polymerase inhibitor sofosbuvir (Sovaldi).

Gilead pulled the plug on trials of daclatasvir plus sofosbuvir, but now that the latter drug is on the market, BMS plans to test a combination of daclatasvir, asunaprevir, its non-nucleoside polymerase inhibitor BMS-791325, and sofosbuvir taken for just 4 weeks, according to a recent Reuters report.

At the International Liver Congress in April, the European Association for the Study of the Liver (EASL) issued new hepatitis C treatment guidelines that took the unusual step of recommending daclatasvir as a component of combination therapy even prior to its approval. The U.S. FDA is currently reviewing daclatasvir plus asunaprevir, which has been designated as a "breakthrough therapy".

Below is an edited excerpt from a Bristol-Myers Squibb press release describing the CHMP opinion.

Bristol-Myers Squibb Receives Positive CHMP Opinion for Daklinza (Daclatasvir) for Treatment of Chronic Hepatitis C in the European Union

Daklinza in combination with other agents would offer a potential cure for HCV patients with high unmet needs who urgently require treatment, if approved

Princeton, N.J. -- June 27, 2014 -- Bristol-Myers Squibb Company (NYSE:BMY) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending that Daklinza (daclatasvir), an investigational, potent pan-genotypic NS5A complex inhibitor (in vitro), be granted approval for use in combination with other medicinal products for the treatment of chronic hepatitis C virus (HCV) infection in adults. This is the first positive opinion given by the CHMP for an NS5A complex inhibitor and will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union (EU).

"Through Bristol-Myers Squibb’s Early Access Programs in Europe more than 2,000 HCV patients with advanced liver disease have already been treated with Daklinza, in combination with sofosbuvir," said Elliott Levy, Head of Specialty Development, Bristol-Myers Squibb. "We anticipate that, if approved, Daklinza-based regimens will play a significant role in treating HCV patients with high unmet medical needs across Europe."

Recently included in the European Association for the Study of the Liver’s (EASL) clinical practice guidelines for the management of HCV infection across genotypes, the EU marketing authorization application for Daklinza has gone through an accelerated review process. The positive CHMP opinion was based on data from multiple studies of Daklinza with other HCV agents, including sofosbuvir, for the treatment of chronic hepatitis C.

Applications for Daklinza-based regimens are also pending in Japan and the U.S. A decision from Japan’s Pharmaceutical and Medical Devices Agency is expected soon, and the U.S. Food and Drug Administration has granted priority review status and set a target review date under the Prescription Drug User Fee Act (PDUFA) of November 30, 2014.

Ongoing and completed Daklinza studies have included more than 5,500 patients in a variety of all-oral regimens and with the current interferon-based standard of care. Across clinical studies, Daklinza-based regimens have been generally well tolerated with low rates of discontinuations across a range of patients.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, an investigational, potent pan-genotypic NS5A complex inhibitor (in vitro), which continues to be investigated in multiple treatment regimens and in people with co-morbidities.

Daclatasvir is being studied in combination with sofosbuvir in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV coinfected patients, and patients with genotype 3, as part of the ongoing Phase III ALLY Program.

In 2014, the U.S. Food and Drug Administration (FDA) granted Bristol-Myers Squibb’s investigational Daclatasvir Dual Regimen (daclatasvir + asunaprevir) Breakthrough Therapy Designation for use as a combination therapy in the treatment of genotype 1b HCV infection.

In 2013, Bristol-Myers Squibb’s investigational all-oral 3DAA Regimen (daclatasvir/asunaprevir/BMS-791325) also received Breakthrough Therapy Designation in the U.S., which helped to expedite the start of the ongoing Phase III UNITY Program. Study populations include non-cirrhotic naive, cirrhotic naive and previously treated patients. The daclatasvir 3DAA regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

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.

6/27/14

Sources

Bristol-Myers Squibb. Bristol-Myers Squibb Receives Positive CHMP Opinion for Daklinza (daclatasvir) for Treatment of Chronic Hepatitis C in the European Union. Press release. June 27, 2014.

B Berkrot. A 4-week hep C cure? Bristol to test drugs with Gilead's Sovaldi. Reuters. June 20, 2014.