Novartis has strengthened its hand in products for treating hepatitis C by licensing exclusive worldwide rights (excluding Japan) to a potential first-in-class antiviral, Debio 025 (alisporivir), from fellow Swiss firm Debiopharm.
Novartis is already developing another hepatitis C therapy, the long-acting alpha-interferon product Joulferon/Zalbin (albinterferon alfa-2b), which was submitted for US and European marketing approval at the end of last year. That product is being developed and co-commercialized in the U.S. with Human Genome Sciences, which filed for FDA approval as Zalbin ('The Pink Sheet' DAILY, November 25, 2009).
The Debiopharm project is in Phase IIb trials. Novartis will make an undisclosed upfront payment to Debiopharm, and that company will also be eligible for milestone payments and royalties on sales. Details were not disclosed. Marketing submissions are not expected before 2014.
It has been a busy last couple of months for Debiopharm, which in January linked up with Pfizer to conduct a Phase III clinical trial of a potential melanoma therapy. The Swiss company specialises in licensing compounds at an early stage, taking them through development, and then licensing them out to pharmaceutical partners - the anticancer Eloxatin (oxaliplatin), launched in 2004 and sold by Sanofi-Aventis, is one of its previous successes. And another of its products, a six-month formulation of triptorelin embonate, Decapeptyl LP , has just been launched in France by its partner, Ipsen.
Host protein interaction
Hepatitis C has attracted significant industry attention in recent years as biotechs and Big Pharma alike scramble to advance new classes of direct-acting antiviral drugs against the virus. But Debio 025 is unlike many compounds in the industry pipeline in that it acts on a target in the infected patient, rather than a target in the virus. The compound is an inhibitor of cyclophilin, a human protein that is co-opted by the virus to help it replicate.
Debiopharm said that the potential advantages of Debio 025 over other antivirals include its high activity against a broad range of hepatitis C virus genotypes, and the possibility of once-daily dosing.
Novartis has been an active in-licensor of experimental hepatitis C therapies. However its luck thus far with Human Genome's Zalbin is balanced by the failures of valopicitabine (a polymerase inhibitor licensed from Idenix Pharmaceuticals) and ANA975 (a toll-like receptor 7 agonist licensed from Anadys Pharmaceuticals). Each molecule was halted in clinical trials over safety concerns ("The Pink Sheet' DAILY, July 2007).
In addition to Zalbin, Novartis' hepatitis C pipeline already includes a cyclophilin inhibitor, NIM811, which is currently in Phase II (Pharmaceutical Approvals Monthly, November 1st, 2009). Novartis hasn't quite cornered that corner of the hepatitis C market. North Carolina-based Scynexis is also developing a cyclophilin inhibitor, SCY-635, which is in Phase I/II trials.
Antivirals nearing the market
Meanwhile the industry's first direct-acting antiviral therapies for hepatitis C are nearing a reckoning with global regulators. Two HCV protease inhibitors, Vertex's telaprevir and Merck's boceprevir, are in Phase III trials. A host of molecules against HCV protease and various other viral targets trail these leaders; eventual combination therapy using two or three such molecules is widely anticipated (IN VIVO, May 2009).
For now, newer single agents are first tested alone and with current standard of care: the generic broad-spectrum antiviral ribavirin and one of two proprietary versions of pegylated interferon alfa, Roche's Pegasys or Merck's PEG-Intron .
In a Phase II study, Debio 025 significantly reduced HCV replication when used alone, the companies say. It also had an additive, anti-HCV effect (4.6 log10 reduction) when used in combination with pegylated interferon alfa-2a in treatment-naïve patients for four weeks. No significant safety issues have been identified so far, nor has long-term efficacy, so-called sustained viral response, been established.
A Phase IIb study is now under way to assess the longer-term safety and efficacy of Debio 025 in combination with standard of care in treatment-naïve patients with HCV genotype 1, the most common variant of the virus in the Western world.
- John Davis (j.davis@elsevier.com)
