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Hot target for HCV
WATERTOWN, Mass.—Enanta Pharmaceuticals Inc., a research and drug development company, has entered into an exclusive collaboration and license agreement with Switzerland-based Novartis for the development of EDP-239, Enanta's lead candidate from its NS5A hepatitis C virus (HCV) inhibitor program. The venture could be worth up to $440 million.
Under the terms of the agreement, Novartis has agreed to pay Enanta $36 million up front, and as much as $404 million more if Enanta hits certain clinical, regulatory and commercial milestones. Enanta is also eligible to receive tiered double-digit royalties on worldwide sales of products, and retains co-development rights in the United States.
Research efforts have shown that targeting NS5A gives rise to profound antiviral activity, and as a result, this protein has emerged as an important target for antiviral drug development, Enanta states.
HCV is a liver disease affecting more than 170 million people worldwide, according to the World Health Organization (WHO). The virus is spread through direct contact with the blood of an infected person. HCV increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death. Liver disease associated with HCV infection is growing rapidly, and there is an acute need for new therapies that are safer and more effective.
Enanta has already received Investigational New Drug (IND) approval for EDP-239 from the U.S. Food & Drug Administration. Under the new deal, Novartis will pick up all costs associated with the development, manufacture and commercialization of EDP-239. Also, Novartis will fund some other compounds that Enanta is working on that target NS5A.
"Novartis is a recognized leader in the field of HCV, and access to its global expertise combined with our shared vision for commercializing HCV therapies will support the successful development and commercialization of products targeting NS5A," Jay R. Luly, president and CEO of Enanta Pharmaceuticals, stated in a Feb. 21 news release. "We believe EDP-239 has great potential as a potent ingredient in combination drug therapy, and our preclinical studies have demonstrated high potency against multiple genotypes of the virus."
Luly tells ddn, "Enanta did not need to partner with Novartis for EDP-239, but there are circumstances for both companies that supported doing the deal now. NS5A is a 'hot target,' and for good reason. Research efforts have shown that targeting NS5A gives rise to profound antiviral activity, and as a result, candidates aimed at this target are being tested in the much-anticipated all-oral, interferon-free drug regimens."
In HCV, pharmaceutical companies are looking at the performance of drug combinations at very early stages in development, he says.
"People are still trying to figure out what the best combinations are," Luly says. "And they are looking to identify the minimum combination of agents that can be put together to effectively treat the virus and stave off the possibility of resistance."
Enanta has now done two early-stage deals "that allow our HCV compounds to participate in multiple potential combination regimens—our HCV protease inhibitor program, ABT-450 is partnered with Abbott, and now our NS5A inhibitor, EDP-239, is partnered with Novartis," he says.
Novartis has a late-stage cyclophilin inhibitor, alisporivir, which it licensed from Debiopharm SA, Luly says. Many believe that the rapid antiviral activity of an NS5A inhibitor and the durable treatment effect from cyclophilin inhibition is a compelling clinical combination.
"There are still several years of clinical development ahead for EDP-239 given that it hasn't started in human clinical trials yet," Luly says. "But there is a broader sense of urgency in the development of new HCV compounds due to the constant threat of drug resistance and the need for therapeutic regimens that are better tolerated and effective—even in the difficult-to-treat genotype 1 cases of HCV."
Luly is aware of the competition among companies to come up with an effective treatment for HCV.
"There are a number of companies developing drug candidates for HCV, some bigger, some smaller," Luly says. " I believe Enanta is unique in that we have applied our novel chemistry approach and drug discovery capabilities to develop one of the broadest pipelines of candidates targeted against HCV. And we are more broadly focused on infectious diseases. We are developing a new class of antibiotics, called cicyclolides, which overcome bacterial resistance."
Novartis spokesman Jeffrey Lockwood is also optimistic about the possibilities of discovering an effective treatment for HCV.
"We believe that oral combination therapy is the likely future of HCV treatment," Lockwood tells ddn. "An NS5A inhibitor is an attractive potential partner for Novartis' cyclophilin inhibitor, Alisporivir (also known as DEB025 in Phase III trials). The combination of a highly potent NS5A inhibitor plus a cyclophilin inhibitor with high barrier to resistance may provide an effective combination for HCV treatment, especially considering that both also have broad genotypic coverage."
In October, Enanta won a five-year, $42.7 million contract from the National Institute of Allergy and Infectious Diseases, a National Institutes of Health division, to support the company's efforts in developing treatments of infections stemming from methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE) and resistant streptococci.