FDA Gives the Green Light for Achillion to Resume Trials with Sovaprevir for Hepatitis C

The US Food and Drug Administration partially lifted a clinical hold on a hepatitis C drug under development by Achillion Pharmaceuticals, clearing the way for a restart of the company’s clinical trials of sovaprevir.

The FDA partially removed the clinical hold on sovaprevir, an NS3/4A protease inhibitor investigational drug for the treatment of the hepatitis C virus. Multiple dose studies of the drug remain on hold but the FDA decision allows additional therapeutic clinical trials of a maximum of 200 mg once-daily dose of sovaprevir in patients with hepatitis C virus to go forward, as well as single dose trials with healthy volunteers, according to a company statement.

So far about 550 trial subjects have taken sovaprevir and the drug was well tolerated when previously evaluated at a once-daily dose of 200 mg in two completed Phase 2 studies, according to a statement released on June 10. Company officials said that they plan to continue to work with the FDA on clinical development of sovaprevir.

The partial clinical hold that remains for multiple dose studies in healthy volunteers requires that the protocol first be reviewed and approved by the FDA. The agency initially placed sovaprevir on clinical hold one year ago because of elevated liver enzymes among some drug recipients involved in a Phase 1 study that evaluated effects of concomitant administration of sovaprevir with ritonavir-boosted atazanavir. To resolve the hold, Achillion was asked to give the FDA study reports from two drug-drug interaction studies along with an integrated safety analysis of ongoing sovaprevir trials.

An FDA clinical hold may apply to one or more investigations covered under a drug company’s approved Investigational New Drug (IND). A hold involving an ongoing study suspends the investigation. Recruitment of new subjects is not allowed and administration of the drug is stopped, unless otherwise permitted by the agency.

Drug companies are in a race to develop the best drugs to treat hepatitis C, a blood-borne virus that if left unchecked can slowly damage the liver, leading to cirrhosis, liver cancer and liver transplant. Health officials have launched public awareness campaigns to encourage screening for the virus because millions of people nationwide and around the world may have the disease and not know it.

Achillion also announced that initial dosing has begun for a patient cohort in a Phase 1 proof of concept trial for another hepatitis C drug. The investigational drug, identified as ACH-3422, is a uridine-analog nucleotide polymerase inhibitor that will be studied for 7 days in patients with genotype 1 chronic hepatitis C.

"With the start of patient dosing with ACH-3422, our Phase 1 uridine-analog nucleotide, we remain on track to report proof-of-concept results in the fall, and plan on initiating all oral combination studies with ACH-3422 by the end of 2014,” David Apelian, MD, Achillion’s chief medical officer said in the prepared statement. “We are also very pleased that the effort by the Achillion team, working in collaboration with the FDA, has resulted in this response for the sovaprevir program.”

Achillion’s hepatitis C drug pipeline will allow it to add protease inhibitors such as sovaprevir to exploration of triple-direct acting antiviral regimens for shorter treatment durations, according to Chief Executive Officer Milind Deshpande. As data from on-going trials emerge, the company will decide how to integrate sovaprevir and other protease inhibitors into combination development programs, the statement said.