Ascletis, a Hangzhou-US clinical stage pharma, reported that China and Taiwan have accepted a clinical trial application to test its dual-drug, interferon-free regimen for chronic hepatitis C. Ascletis is the first China company to achieve this milestone. "There are no direct-acting antiviral agents (DAAs) approved in China, and no China companies have filed to start clinical trials of more than one DAA in China," Dr. Jinzi Wu, Founder, Chairman and CEO of Ascletis, told ChinaBio® Today in an exclusive interview. "We are very competitive against both domestic and multinational pharmas."

Ascletis filed to test a combination of ASC08, a second-generation HCV NS3/4A protease inhibitor, and ASC16, a NS5A inhibitor. Both are DAAs.

In a departure from the norm, Ascletis completed a simultaneous filing in both China and Taiwan. Dr. Wu explained that ASC08 has already completed a Phase II test in Taiwan, which will will accelerate the process in China. "Because the data from the Taiwan trial was so positive," he said, "the CFDA will approve all three phases of the test at the beginning." Otherwise, the company would have to follow the usual procedure and apply for permission to continue after each phase is completed.

Ascletis is proud of being the first-to-file in China for an interferon-free HCV treatment. But it also wants to be first on the market in China. Timelines become critical, as a result. Dr. Wu believes, based on Ascletis' internal analysis, that the company will have a two-year jump over the competition, including the Gilead HCV treatments, Solvadi and Harvoni.

"Because Ascletis' molecules are designated China Class 1.1 innovative drugs [never approved anywhere in the world], the company has a competitive advantage over multinationals," Dr. Wu declared. "Multinational drugs have already been approved elsewhere or are part of multicenter trials. The CFDA gives consideration of their approval requests a lower priority."

Taiwan offers an additional advantage to companies developing drugs for China. The two countries signed an Harmonization Agreement for clinical development in December 2014. "The CFDA and the Taiwan FDA picked four hospitals in China and four in Taiwan. They agreed that clinical trial data from these four sites would be accepted for use by both agencies," Dr. Wu said.

In 2013, Ascletis in-licensed ASC08 (danoprevir). a second-generation HCV NS3/4A  protease inhibitor, from Roche. Ascletis reported data from a Taiwanese Phase II study in March, in combination with interferon and ribavirin. In genotype 1a non-cirrhotic patients, after a 12-week regimen, the SVR12 rate was 94% and in genotype 1b non-cirrhotic patients the SVR12 rate was 100%.

Roche thought the drug might be more effective in Asian patients than among Caucasians, a theory that turned out to be correct.

Before he founded Ascletis, Dr. Wu was Vice President, Global HIV Drug Discovery at GlaxoSmithKline (NYSE: GSK), giving him credibility in anti-viral drug development. At Ascletis, the danovir protease inhibitor HCV treatment from Roche was the second asset the company in-licensed. He knew, he said, that the Roche DAA was very safe and very effective. But the company would need a second DAA molecule to be competitive as a complete interferon-free regimen for HCV.

"We didn't know what the second molecule would be, though I talked with Presidio Pharma fairly early. I knew we must have two DAAs, and we started looking for a second asset from the start," he declared.

In late 2014, Ascletis in-licensed ASC16 (ravidasvir), an NS5A inhibitor and Ascletis’ second DAA, from Presidio Pharma of California. ASC16 may be one of the best-in-class compounds, according to Ascletis. In a US Phase IIa clinical trial, which combined ASC16 and other two DAAs (but no interferon), a group of HCV genotype 1a patients experienced an SVR12 rate of 92% after 12 weeks of treatment.

The high prices of new-generation HCV drugs, especially the Gilead drugs, has been very controversial. Although Ascletis won't get specific about is pricing targets, Dr. Wu declared that "Ascletis is in China for China. We want to be affordable, and we will be less expensive than the Gilead drugs."

Hepatitis C is a large unmet need in China. CCTV recently put the number of patients with HCV at 40 million, which is in the same range as most experts in the field. Of these, about two-thirds or 24 million have genotype 1b. As Dr. Wu is quick to point out, the genotype 1b population is the one in which ASC08 had a 100% cure rate in the recent Taiwan trial.

Ascletis was formed in 2011 with commitments for an amazing $100 million in startup capital. So far, it has announced work on four drug candidates: the two we have already discussed, plus ASC06, a clinical stage, first-in-class, systemically delivered RNAi therapeutic for the treatment of liver cancers licensed from Alnylam Pharma; and ASC09, a next-generation HIV protease inhibitor licensed from Janssen, a division of Johnson & Johnson.

"This is a great business opportunity for Ascletis to market a DAA in China," Dr. Wu said, summing up. " It was already on my mind five years ago and now Ascletis is in a position to deliver."

See our other articles on Ascletis.

Disclosure: none.