SMA: RG3039 Proves Safe in Phase 1 Trial

In a phase 1 trial in healthy volunteers, Repligen's experimental therapy for spinal muscular atrophy was safe and well-tolerated

Article Highlights:
  • Repligen Corp. announced positive results for its phase 1 safety trial of RG3039, an experimental treatment for spinal muscular atrophy (SMA).
  • RG3039 was found to be safe and well-tolerated in 32 healthy volunteers. Data also showed that the therapy reached and worked on its biological target.
  • RG3039 is a small-molecule therapy designed to increase cellular levels of the SMN protein, which is deficient in SMA.
  • A $1.4 million MDA grant supported completion of the preclinical steps required for advancing RG3039 to testing in humans and helped support the phase 1 trial.
by Amy Madsen on April 25, 2012 - 4:00am

Update (June 21, 2012): This story was updated to include the fact that MDA funding helped support the phase 1 trial, as well as the preclinical development of RG3039.

RG3039, an experimental therapy designed to treat spinal muscular atrophy (SMA), was safe and well-tolerated in a phase 1 clinical trial. In addition, data suggests the drug reached and worked on its biological target, an enzyme called DcpS.

Results for the trial, the first of a drug specifically designed to treat SMA, were announced by biotech company Repligen Corp., of Waltham, Mass., on April 25, 2012, at the 2012 meeting of the American Academy of Neurology taking place in New Orleans.

RG3039 is a small-molecule compound designed to increase cellular levels of the SMN protein, which is deficient in SMA.

MDA helped pave the way to the phase 1 trial with a $1.4 million grant to Repligen in December 2010.

Phase 1 study focused on safety

RG3039 was tested in 32 healthy human volunteers, each of whom received a single dose of the drug. The trial was designed to determine safety, tolerability and pharmacokinetics (the way the body affects a drug).

Results indicated that RG3039 is safe and well-tolerated at several dose levels. A dose-dependent drug response was seen, with greater effect at higher doses. In some cases RG3039 inhibited the activity of the target enzyme, DpcS, by up to 90 percent.

Pending approval by the U.S. Food and Drug Administration (FDA), Repligen plans to conduct a second phase 1 study, this time in people with SMA. If favorable results are obtained in this second safety study, RG3039 may advance to later-stage efficacy trials. (A drug's efficacy is its ability to produce a desired effect.)

RG3039 increases production of SMN protein

RG3039 is designed to increase levels of fully functional SMN protein produced by the SMN2 gene. (SMN stands for “survival of motor neuron.”)

The experimental therapy has been shown to increase production of SMN protein in cells taken from people with SMA, and to improve mobility, life span and the health of nerve cells (motor neurons) in animal models of the disease.

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. RG3039 was licensed by Repligen from the patient organization Families of SMA, which fully funded and directed its preclinical development.

MDA support for RG3039

MDA's $1.4 million award to Repligen helped support the phase 1 trial, as well as mouse studies to determine the optimum dose of RG3039 in humans, and the identification of biomarkers to monitor the drug's effects in the body.

Part of MDA's award also supported completion of the final stages of RG3039's preclinical development. These included the manufacturing of sufficient quantities of clinical-grade RG3039 for use in testing, and submission to the FDA of an investigational new drug (IND) application.

The grant was awarded through MDA's translational research program, which funds the transition of promising experimental drugs from preclinical development through the testing required to qualify for government approval for marketing.

About Clinical Trials

About Clinical Trials

A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur.

MDA has no ability to influence who is chosen to participate in a clinical trial.

To learn more, see Understanding Clinical Trials and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to

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