SMA: Repligen Launches Phase 1b Trial of RG3039

The experimental drug RG3039, being developed by Repligen Corp. of Waltham, Mass., as a potential treatment for spinal muscular atrophy (SMA), has moved into its next phase of testing.

RG3039 previously was tested in a phase 1a trial, in which healthy adult volunteers received a single dose of the drug. Now, in a phase 1b trial, healthy volunteers will receive multiple doses of the drug.

By inhibiting the activity of an enzyme called DcpS (scavenger decapping enzyme), RG3039 may increase levels of the SMN (survival of motor neuron) protein, which is deficient in SMA.

A $1.4 million MDA grant awarded to Repligen in December 2010 is helping to support the new trial.

Phase 1b trial tests multiple doses in adult volunteers

In the new phase 1b trial, 24 volunteers will take multiple doses of either RG3039, and eight will receive an inactive substance (placebo).   

The trial is designed to evaluate the safety and pharmacokinetics (the ways in which a drug is absorbed, distributed, metabolized and eliminated by the body) of multiple doses of RG3039 in healthy adult volunteers. In addition, the researchers plan to determine what levels of RG3039 are needed in the body to achieve sufficient inhibition of DcpS.

"Completion of this stage of the RG3039 clinical development program in healthy volunteers, if successful, will provide the necessary foundation for more advanced trials involving SMA patients who are in critical need of a treatment for this devastating disease," said Repligen's President and CEO Walter C. Herlihy. "We appreciate the support of our collaborators in conducting this phase 1b trial and look forward to sharing the results."

Previous encouraging results

In preclinical testing, RG3039 was shown to increase production of the SMN protein in cells derived from people with SMA. In addition, RG3039 has been shown to improve the health of nerve cells called motor neurons, preserve mobility and increase life span in animal models of SMA.

Encouraging results from Repligen's phase 1a trial of RG3039, presented at the annual meeting of the American Academy of Neurology (AAN) in April 2012, demonstrated that RG3039 was well-tolerated at levels even greater than those at which its target, cellular DcpS, was inhibited. The data showed evidence of a dose-related drug response, with greater effect at higher doses. In some cases, RG3039 inhibited DpcS by up to 90 percent.

The outcomes from both phase 1 studies are expected to inform the approach and design of a future efficacy study of RG3039 in people with SMA.

MDA support for RG3039

MDA's $1.4 million grant to Repligen in December 2010 is helping to support the new trial. Funds from that award also supported completion of the final stages of RG3039's preclinical development, including the manufacturing of sufficient quantities of clinical-grade RG3039 for use in testing, and submission to the U.S. Food and Drug Administration (FDA) of an investigational new drug (IND) application.

“We are pleased to see the continued development of this important therapy for individuals with SMA," said MDA Vice President of Research Sanjay Bidichandani.

The FDA has granted RG3039 fast track and orphan drug designations. A fast track designation allows for faster review of drugs that treat serious diseases and fill an unmet need, while orphan drug status provides economic incentives to companies developing treatments for rare diseases.

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