FDA Puts Clinical Hold on Studies of Investigational MicroRNA Drug

The Food and Drug Administration recently placed a clinical hold on human trials involving a new investigational hepatitis C drug that targets microRNA following a report of jaundice by someone enrolled in a study, the drug developer Regulus Therapeutics announced.

Regulus said in a statement that the company learned of a clinical hold on RG-101, its investigational new drug, via a verbal notice from the FDA. The hold was initiated after Regulus, a San Diego-based company, reported a second serious adverse event (SAE) of jaundice, according to the statement.

“Regulus anticipates it will receive a formal clinical hold letter from the FDA within 30 days and plans to work diligently with the agency to seek the release of the clinical hold,” company officials said in the statement.

A patient with hepatitis C experienced jaundice 117 days after taking a single dose of RG-101, the statement said. The patient, who has end-stage renal disease and was on dialysis, was enrolled in the Regulus ongoing phase 1 US drug trial, according to the company statement.

In a conference call about the FDA action, Paul Grint, President and CEO of Regulus, said that the patient with jaundice had elevated bilirubin lab results and was hospitalized for further evaluation. The patient was later released in stable condition and the study investigator assessed the SAE as unlikely related to RG-101, he said.

The recent SAE was the second case of jaundice involving patients who received RG-101, Grint said. Both patients also had type 2 diabetes and the first SAE occurred earlier his year and involved a patient who also received RG-101 in a Phase 2 trial, he said.

“It is our understanding that given that the mechanisms for these two events appear uncertain at this time, the FDA considered it appropriate to issue a clinical hold,” Grint said.

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

All patients enrolled in the Phase 1 trial and two other studies have already completed dosing of RG-101 so timelines for those studies are not expected to be impacted by the FDA clinical hold, according to Grint. Patients involved in the studies will continue with protocol-scheduled visits and Regulus expects “to remain on track” to present follow-up results at upcoming scientific meetings, the statement said.

The investigational drug RG-101 targets microRNAs, with a unique approach to treating the disease by modulating entire biological pathways, according to the statement. The drug, which is administered as an injection, has also been tested in a study conducted in Budapest, Hungary, according to research presented earlier this this year at the International Liver Congress in Barcelona.

Grint said his company will decide what action to take once it has received the formal clinical hold letter from the FDA.

“Clearly we are waiting for the FDA letter, and then absolutely our goal is to answer their questions as rapidly and as completely as we can,” he said.