Regulus off by more than half on FDA clinical trial hold for lead in hep C

FDA sign

Regulus Therapeutics ($RGLS) shed 54% in after-hours trading on news that the FDA placed a clinical trial hold on its lead candidate, RG-101 to treat hepatitis C. The hold is due to safety concerns triggered after a second case of jaundice emerged in a Phase I trial after the patient received a single dose of RG-101.

The candidate, which is intended to cure hepatitis C with just a single dose, is partnered with GlaxoSmithKline ($GSK). RG-101 targets microRNA-122, which the virus uses to replicate.

“Given that the mechanism for these two events is uncertain at this time, the FDA considered it appropriate to issue a clinical hold,” said Regulus CEO Dr. Paul Grint on a June 27 conference call regarding the clinical hold.

The company said it had received verbal notice from the FDA, but that it anticipates a formal clinical hold letter within 30 days. It said it will work with the agency to lift the clinical hold.

Regulus said that its three ongoing studies of RG-101 should not be affected, since all patients have been enrolled and already completed their single dose of the candidate.

The company reported positive top-line Phase II data for RG-101 in early June. And it was also slated to be in a Phase II trial in combination with partner GlaxoSmithKline’s long-acting parenteral formulation of GSK2878175 starting in the fourth quarter; data from that trial were anticipated during the second half of next year. GSK just expanded a deal with Regulus earlier this month to conduct that trial.

In March, the pair started a Phase II study of RG-101 in combination with daily oral GSK2878175 for up to 12 weeks in treatment-naïve patients chronically infected with HCV genotypes 1 and 3. Dosing has been completed in that trial with interim data due before year end.

This latest serious adverse event was a case of jaundice that occurred in an ongoing Phase I trial, 117 days after receiving one dose of RG-101. The HCV patient had end-stage renal disease and was on dialysis.

Regulus said it’s “unlikely” that the latest event was related to RG-101, noting that the patient had Type 2 diabetes that was controlled with insulin, coronary artery disease, high cholesterol and high blood pressure and was on a dozen medications

A prior case of jaundice was reported in a Phase II combination trial earlier this year. That patient had one dose of RG-101 as well as four weeks of oral Daklinza that was followed by a second dose of RG-101 on day 29.

“Once we receive the letter from the FDA, I'm sure there going to be additional analysis and things that we're going to have to perform and we will obviously make that our utmost priority and we'll turn everything round and provide it back to the FDA as fast as we can,” summed up Grint on next steps for Regulus.

- here is the release

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