Aim is to combine ALS-2200 and ALS-2158 with approved Incivek and investigational candidate VX-222.
Vertex Pharmaceuticals is paying Alios BioPharma $60 million up front for worldwide rights to two of the latter’s preclinical hepatitis C candidates, ALS-2200 and ALS-2158. Alios could also receive R&D-related milestones of up to $715 million if both compounds are approved, an additional $750 million in sales milestones, plus tiered sales royalties.
As part of their partnership the firms are also establishing a research program focused on the discovery of additional nucleotide analogues acting on the hepatitis C polymerase. Vertex will retain an option to select resulting compounds for future development.
Phase I studies with both HCV polymerase inhibitors are projected to start during the latter part of this year. Under terms of the deal Vertex will shoulder all development costs for both drugs and will also provide Alios with research funding.
The deal with Alios comes just weeks after FDA approved Vertex’ oral HCV protease inhibitor Incivek™ (telaprevir) for treating genotype 1 chronic HCV patients with compensated liver disease in combination with pegylated-interferon and ribavirin. It says the Alios compounds will provide the potential to expand its HCV franchise to territories outside of North America.
ALS-220 and ALS-2158 both target the HCV NS5B polymerase but have different mechanisms of action, providing the potential to develop the drugs as dual regimens either together or as part of combination therapy with Incivek or Vertex’ clinical-stage investigational non-nucleosidase polymerase inhibitor VX-222. Both ALS-2200 and ALS-2158 have already demonstrated synergistic effects when combined with the two Vertex drugs, the firms note.
Initial Phase I studies with ALS-2200 and ALS-2158 will be designed to generate data needed to progress the candidates into Phase II development potentially in 2012. The Phase II program will evaluate multiple combination regimens of ALs-2200, ALS-2158, Incivek, and VX-222.
“Together we have the potential to create an all-oral, interferon-free combination therapy that could improve the safety, efficacy, and ease of administration for patients,” comments Lawrence M. Blatt, Ph.D., Alios’ founder and CEO.
Alios is focused on the development of antiviral drugs based on three complementary platforms: small molecule activators of innate immunity antiviral pathways (RNase L activation), phosphate protected nucleotide prodrug chemistry, and interferon glycoprotein engineering (Glycoferona). The firm claims these platforms provide the potential to generate therapeutics targeting a range of serious viral infections including chronic hepatitis B and C, HIV, respiratory viruses and emerging viral diseases.
Alios’ nucleoside analogue program hinges on the development of nucleoside monophosphate prodrugs that bypass the need to generate monophosphate forms of a nucleoside. It claims the resulting compounds have demonstrated excellent potency against the hepatitis C virus in vitro and shown promising preclinical in vitro and in vivo safety profiles.
At the end of March Vertex reported promising interim data from an ongoing Phase II study (Zenith) evaluating the safety and tolerability of VX-222 combined with Incivek, pegylated-interferon, and ribavirin in 106 previously treatment-naïve patients with genotype 1 chronic hepatitis C. The Zenith study data showed that 90% of patients receiving VX-222 (400 mg) in combination with telaprevir, pegylated-interferon, and ribavirin had undetectable hepatitis C virus at week 12, and 50% of patients in the VX-222 (400 mg) treatment group were eligible to stop all treatment at week 12. An intent-to-treat analysis showed that 57% of patients on the quadruple regimen actually had undetectable hepatitis C virus by week two.