HONG KONG – The recent approval of all-oral hepatitis C virus (HCV) drug RDV/DNV, a combination of Asclevir (ravidasvir) and Ganovo (danoprevir), helped boost shares of Ascletis Pharma Inc. (HK:1672), which ended July with a 10% jump to HK$3.36 (US43 cents), as the Hangzhou, China-based company continues to push its pipeline of treatments forward and improve its outlook.
The company’s NDA for Asclevir, a NS5A protein inhibitor with pan-genotypic antiviral activity, was accepted in 2018, while Ganovo, a NS3/4A protease inhibitor, was approved for commercialization by China’s National Medical Products Administration (NMPA) in 2018, making it the company’s third marketed product in China. Approval of the combination regimen was based on data from phase II and III trials showing it had a 99% cure rate and achieved a sustained virologic response (SVR) and no detectable amount of HCV after 12 weeks of treatment in genotype 1 patients. For patients with baseline NS5A resistance mutations, the regimen demonstrated a cure rate of 100%.
“The biggest innovation of the treatment is the use of potent oral antiviral drugs to replace interferon, which has a longer treatment time,” Chenlin Li, spokeswoman for Ascletis told BioWorld. “Previous HCV treatments combined interferon with ribavirin, which meant that treatments lasted anywhere from 24 to 48 weeks. The all-oral regimen not only shortens the treatment course to 12 weeks, but also greatly improved the cure rate of the disease to 95% from 50% to 70% previously.”
With a different antiviral compound, the regimen is also less likely to trigger adverse reactions. Compared with triple direct-acting antiviral (DAA) treatments involving grazoprevir, ruzasvir and uprifosbuvir, which has a treatment time of up to 24 weeks, patients who use the full-oral regimen for treatment no longer need weekly subcutaneous injections of interferon, which greatly reduces the incidence of adverse reactions during treatment, improving their tolerance for the regimen.
“Side effects of the new regimen include rashes, headaches and diarrhea, much lighter than those of traditional therapies such as fever, flu-like symptoms or even blood abnormalities,” said Li.
The new regimen is also an important step in eliminating the HCV virus from patients’ bodies. With previous treatments, patients can be “cured” of the disease, achieving SVR. However, traces of the virus still linger in the body, which could lead to relapses or chronic conditions in rare cases.
“Traditional interferon therapies work by activating the body’s immune response to kill the HCV virus which works. However, DAA therapies such as the new oral treatment are far superior in terms of efficacy as they directly inhibit certain receptors in the liver which the virus attaches on to cause an infection, allowing the body to be rid of the virus near completely,” said Li.
Both ravidasvir and danoprevir have been listed as Innovative Drug Development programs by the Development Center for Medical Science & Technology in China.
Ravidasvir was licensed from Presidio Pharmaceuticals Inc., while danoprevir was licensed from Roche Holding AG, with Ascletis holding commercial rights in greater China for both drugs.
Ascletis is now looking to strengthen its pipeline of products to treat chronic hepatitis B. Under development is a first-in-class immunotherapy, the subcutaneously injected PDL-1 antibody ASC-22. The product is already undergoing phase II trials.
“ASC-22 is expected to become the world’s first PD-L1 antibody immunotherapy drug for hepatitis B. It can effectively improve the function of specific T cells by blocking the PD-1/PD-L1 pathway. It remains stable at room temperature, and can be administered through subcutaneous injection,” said Li.
Other products in the company’s pipeline include ASC-09, a potential best-in-class protease inhibitor to treat HIV type-1 infections. ASC-09 has completed phase I and phase IIa trials, which have shown that ASC-09 has potent antiviral activity, contributing to up to a 1.79 log viral load decrease (62-fold reduction of viral load in blood samples of patients) after two weeks of treatment of monotherapy.
ASC-09’s genetic barrier to resistance is also a highlight. Studies have shown that more than seven mutations are required before HIV develops resistance to ASC-09, a much higher number compared to other approved protease inhibitors. The company plans to initiate the product’s phase IIb trial this year.
Another product in development is ASC-06, the first systematically delivered therapeutic drug to treat liver cancer by using RNA interference. ASC-06 works by silencing two genes critical for growth of liver cancer cells, specifically VEGF and kinesin spindle protein.
ASC-06 has already gone through phase I and phase II trials, which showed that 50% of patients who received a ≥0.7-mg/kg dose achieved stabilized conditions and that the drug is generally safe and well-tolerated. The company also plans to initiate a phase II trial in China this year.