Ascletis Pharma, a Hangzhou clinical stage biopharma, has been approved to begin a Phase II trial in Taiwan of its dual-drug, interferon-free treatment for chronic hepatitis C. The regimen consists of two Ascletis direct-acting antivirals (DAAs) that will be administered for 12 weeks. "We expect the dual drug regimen will be comparable to Gilead's (NSDQ: GILD) Harvoni in efficacy and safety," Dr. Jinzi Wu, Founder, Chairman and CEO of Ascletis, told ChinaBio® Today in an exclusive interview. "But because we are a China company, our regimen will be more affordable."

"There are no direct-acting antiviral agents approved in China, and no China companies have filed to start clinical trials of more than one DAA in China," Dr. Wu added. "Also, we are the only China company to have two HCV regimens in China trials." Ascletis' other regimen is a combination of two DAAs and pegylated interferon alpha, which would compete with Gilead's second HCV treatment, Sovaldi.

The two Gilead blockbuster drugs are very effective against HCV genotype 1, but they are also controversial because of their cost: over $80,000 for a 12-week treatment.

Ascletis' two-drug regimen for HCV consists of ASC08, also known as danoprevir, an HCV NS3/4A protease inhibitor licensed from Roche in 2013 (see story); and ASC16, a clinical stage HCV NS5A inhibitor licensed from Presidio Pharmaceuticals in 2014 (see story).  

Dr Wu said his prediction that Ascletis' dual therapy would rival Harvoni is based on the preclinical data of ASC16, the HCV NS5A inhibitor, and the data from trials of similar drugs from other manufacturers. He expects a sustained virologic response in at least 90% of the patients, and he is hoping for higher than that. Harvoni is a combination of two HCV NS5 inhibitors.

Ascletis plans to conduct trials in both Taiwan and mainland China even though some data sharing is allowed between the two countries. In Taiwan, the TFDA allowed Ascletis to begin testing of the regimen at Phase II because each of the two drugs has been tested separately.

Dr. Wu expects the China FDA to rule on the IND in early 2016. "If we have strong data from our Taiwan trial, we are hoping to be granted Super Approval," he said. "That means we would be able to move directly from one phase to the next, without applying to the CFDA for approval each time."

According to Ascletis, the Taiwan study, named EVEREST, will begin in September 2015. It is designed to evaluate the antiviral activity, safety and pharmacokinetics of the regimen in treatment-naive HCV Genotype 1 non-cirrhotic patients. The primary endpoint is sustained virologic response at 12 weeks post-treatment (SVR12). Both ASC16 and ASC08 are well tolerated, and each has shown strong antiviral activity in prior clinical trials.

ASC08 has been evaluated in 27 Phase I and 7 Phase II clinical trials with a total of approximately 2400 healthy volunteers and patients tested. The DAPSANG (Phase II study in Taiwan) results show that after 12-week treatment of ASC08 in combination with PEG-IFN and ribavirin, the SVR12 rate observed in genotype 1 non-cirrhotic patients in Taiwan was 94% and in genotype 1b non-cirrhotic patients the SVR12 rate was 100%.

ASC16, also known as ravidasvir, is a pan-genotypic NS5A inhibitor. In a Phase IIa clinical trial in patients with HCV genotype 1a infection, an IFN-free regimen containing ASC16 and other two DAAs was well tolerated and had an SVR12 rate of 92% after 12 weeks of treatment.

Traditionally, the regimen for treatment of hepatitis C has been a 48-week course of interferon and ribavirin. Neither one is a direct-acting antiviral, and the regimen is only about 50% effective in patients with HCV genotype 1. Because interferon typically causes flu-like symptoms, the long-term regimen is difficult to tolerate.

“Due to the long treatment duration, significant adverse effects and various kinds of contraindications, many patients cannot tolerate treatment with interferon.” said Professor Zhuang Hui, academician of the Chinese Engineering Academy and the honorary Chairman of the Chinese Society of Hepatology, at Peking University Health Science Center, “Ascletis is the first domestic company in China to conduct clinical trials of an all-oral IFN-free HCV regimen.”

“Therapies based on DAAs have predominated the chronic hepatitis C markets in the developed countries; however, there are no DAAs approved in China yet and the combination of PEG-interferon-alpha and ribavirin is still widely used as the Standard of Care,” said Ascletis' Dr. Wu in a statement. “It is Ascletis’ vision to bring breakthrough treatments to the Chinese market. With two DAAs in the pipeline, we are developing a triple therapy (ASC08 in combination of PEG-IFN/ribavirin for 12 weeks) and an all-oral-IFN-free therapy to meet different clinical needs of patients. We believe that the EVEREST study will provide safety and efficacy data to support further development to the market, since we want to bring Chinese HCV patients an affordable all-oral IFN-free regimen.”

Formed in 2011 with $100 million in startup capital, Ascletis has in-licensed four late-stage candidates: besides ASC08 and ASC16, these are ASC06, a clinical stage, first-in-class, systemically delivered RNAi therapeutic for the treatment of liver cancers licensed from Alnylam Pharmaceuticals; and ASC09, a next-generation HIV protease inhibitor licensed from Janssen, a Johnson & Johnson company.

As a young company, Ascletis hasn't detailed its late-development strategy. But Dr. Wu said, "Ascletis has R&D, manufacturing and regulatory capability. So we want to do that. There are several options for commercialization. One of those would be our partner Roche, which discovered one of the two DAA agents and has a strong commercialization operation. But other options exist as well."

Timelines are important, and there are too many variables in clinical trials to predict when Ascletis' regimens will be granted approval. However, Dr. Wu does harbor one hope: "If things go well for us, we could be the Harvoni in China -- we could be the first to market."

See our other articles on Ascletis.

Disclosure: none.