Enanta Pharmaceuticals, a research and development-focused biotechnology company, announced that AbbVie, Enanta’s collaboration partner for ABT-450, has submitted a New Drug Application (NDA) to the US Food and Drug Administration seeking approval for an investigational, all-oral, interferon-free regimen for the treatment of adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection.

The three direct-acting antiviral regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. ABT-450 is the lead protease inhibitor developed through Enanta’s collaboration with AbbVie.

The US NDA filing triggers a $20 million milestone payment to Enanta from AbbVie. AbbVie also plans to submit applications for regulatory approval of its regimen in the European Union in early May. Enanta is entitled to receive an additional $20 million upon the first regulatory filing in the European Union for a regimen containing a collaboration compound.

The NDA is supported by AbbVie’s data from the largest all-oral, interferon-free clinical programme in GT1 patients conducted to date,1 with six phase 3 studies that included more than 2,300 patients in over 25 countries.

“This submission marks a very significant step toward Enanta being part of the first wave of all-oral therapies that may be approved to treat patients with genotype 1 hepatitis C virus,” stated Jay R. Luly, president and chief executive officer, Enanta Pharmaceuticals.  “No all-oral therapy has yet been approved to treat GT1 HCV infection, which is estimated to affect approximately 70 per cent of the 3.2 million people of the US population infected with HCV.”2

In May of 2013, AbbVie's investigational direct-acting antiviral (DAA) regimen with and without ribavirin for HCV genotype 1 was designated as a Breakthrough Therapy by the US FDA. This designation is intended to help expedite the development of drugs for serious or life-threatening conditions and is based in part on preliminary clinical evidence demonstrating a drug or regimen may have substantial improvement on at least one clinically significant endpoint compared to available therapy.

In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialisation of HCV NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing drug combinations. ABT-450 is a protease inhibitor identified as a lead compound through the collaboration. Under the agreement, AbbVie is responsible for all development and commercialisation activities for ABT-450.

Enanta received $57 million in connection with signing the collaboration agreement, has received $55 million in subsequent clinical milestone payments, is entitled to receive $20 million in connection with the NDA filing in the US described above, and is eligible to receive up to an additional $175 million in payments for regulatory and commercialisation milestones, as well as double-digit royalties worldwide on any revenue allocable to the collaboration’s protease inhibitors.

Also, for any additional collaborative HCV protease inhibitor product candidate developed under the agreement, Enanta holds an option to modify the US portion of it rights to receive milestone payments and worldwide royalties. With this option, Enanta can fund 40 percent of US development costs and US commercialisation efforts (sales and promotion costs) for the additional protease inhibitor in exchange for 40 per cent of any US profits ultimately achieved after regulatory approval, instead of receiving payments for US commercial regulatory approval milestones and royalties on US sales of that protease inhibitor.

ABT-450 is an NS3 protease inhibitor discovered through Enanta’s ongoing collaboration with AbbVie. AbbVie and Enanta have an agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors. Protease inhibitors play an essential role in the viral life cycle of the hepatitis C virus (HCV). Inhibition of the protease prevents non-structural (NS) proteins from forming and thereby prevents replication and survival of the HCV virus. ABT-450 is part of AbbVie’s investigational regimen for HCV that consists of boosted protease inhibitor ABT-450/ritonavir (referred to as ABT-450/r), NS5A inhibitor ABT-267 and non-nucleoside polymerase inhibitor ABT-333.