In the field of hepatitis C virus (HCV) protease inhibitors, Enanta Pharmaceuticals Inc. now has added its name to the list of players.
The Watertown, Mass.-based company signed an agreement with Chiron Corp. to develop and commercialize a preclinical portfolio of HCV protease inhibitors. The deal includes compounds generated from an earlier collaboration between the companies, as well as compounds Chiron developed on its own. Enanta gains exclusive rights in exchange for development milestone payments and royalties.
Enanta and Chiron previously worked together with Enanta's chemistry platform to develop therapeutics for HCV, and, at the conclusion of the 2002 collaboration, Chiron was able to select a predetermined number of compounds, said Jay Luly, president and CEO of Enanta.
The new deal "puts the entire HCV portfolio into Enanta's hands," he said, adding that the company will begin by optimizing the compounds, then nominating a drug candidate to take into the clinic, hopefully in 2006.
Financial terms of the deal were not disclosed, but Chiron will retain options for co-development and commercialization rights worldwide, with the exception of Asia, in which Enanta will be able to seek a partnership for that region.
Emeryville, Calif.-based Chiron, which cloned and first identified HCV as the cause of transfusion-related non-A, non-B hepatitis, also granted Enanta a nonexclusive license to its HCV technology for research and development purposes.
Privately held Enanta might be better known as a company developing macrolide and ketolide antibiotics for community respiratory infections, Luly told BioWorld Today, though the HCV program is a nice fit strategically.
"It's consistent with our theme at Enanta, to work with small molecules to take on big commercial opportunities," he said.
The existing standard of care for HCV is peginterferon plus ribavirin, though neither of those has a direct antiviral effect. HCV protease inhibitors still are in early stage development, but they already have shown promise in reducing viral load. A 14-day Phase I study of Cambridge, Mass.-based Vertex Pharmaceuticals Inc.'s VX-950 demonstrated a 4 log reduction in viral load in patients receiving 750 mg of the HCV protease inhibitor three times per day.
"We are seeing substantial, really stunning viral load decreases within two or three days of treatment," said analyst Andrew McDonald, of ThinkEquity Partners in San Francisco, referring to the study by Vertex and promising preclinical work with HCV protease inhibitor 1HO6 by Brisbane, Calif.-based InterMune Inc.
Drugs targeting the HCV protease could be "potential blockbusters," he said. "Over the next couple of years, that space is going to become incredibly hot, and I think you'll see revolutionary results in clinical studies."
Along with Vertex's product, McDonald said he knows of only one other drug in the clinic, SCH7, by Kenilworth, N.J.-based Schering-Plough Corp., though no data have been reported on that product.
Luly said the validation of HCV protease inhibitors in other studies reinforced Enanta's interest in developing the compounds. Another point of interest was the competitive field, which at this stage, has "no dominant player that has captured the entire space," leaving room for other small molecules to come forward.
McDonald agreed, and said there is a "wide-open landscape," in an HCV market that could total $3 billion worldwide. "I think any of these direct antivirals could achieve sales of $1 billion."
As the products advance through the clinic, researchers also might consider combining the protease inhibitors with other therapeutics. Idenix Pharmaceuticals Inc., of Cambridge, Mass., is developing an HCV drug designed to inhibit polymerase, NM 283, which is in a Phase IIb study. Like protease, polymerase is a target in the HCV life cycle, and the two could potentially work together in combination therapy, McDonald said. Peginterferon also might be added in a triple-therapy approach.
"When I look into the future, I see a combination approach, much like you have with HIV," McDonald told BioWorld Today, but the treatments would look to cure the infection.
Existing therapies have a cure rate of about 40 percent in patients infected with genotype 1 HCV, the most prevalent strain of the virus in the U.S., Western Europe and Japan, representing about 70 percent of that HCV patient population. With combination therapy, "I think you'll see cure rates around 90 percent or greater," McDonald added. But if that holds true, companies could have a limited time to get their drugs to the market, maybe as few as 10 years.
"As these drugs reach the market, I believe HCV will essentially disappear as an unmet medical need," he said.
Shares of Chiron (NASDAQ:CHIR) gained 43 cents Thursday to close at $36.72.