Repligen Initiates Phase 1b Trial of RG3039 for Spinal Muscular Atrophy Licensed from Families of SMA.

Post date: May 17, 2013 2:54:57 PM

September 26, 2012.

Repligen Initiates Phase 1b Trial of RG3039 for Spinal Muscular Atrophy Licensed from Families of SMA.

Repligen Corporation has initiated a Phase 1b clinical study of RG3039, a novel small molecule drug candidate for the potential treatment of spinal muscular atrophy (SMA).  The primary objectives of the study are to further evaluate the safety and plasma pharmacokinetics (PK) of multiple doses of RG3039 in healthy volunteers.

Repligen licensed RG3039 in 2009 from Families of Spinal Muscular Atrophy (FSMA).  FSMA funded and directed the preclinical development of RG3039 with an investment of more than $13 million.  This was the first drug discovery program ever conducted specifically for SMA.

Phase 1b Study Design:

This Phase 1b trial is a double-blind, placebo-controlled, ascending multiple dose study, being conducted at the Jasper Clinic in Kalamazoo, Michigan.  According to the study protocol, each of 32 adult healthy volunteers will be randomized to receive ascending oral doses of either RG3039 or placebo.  Within each of the four dose cohorts, six subjects will be exposed to oral doses of RG3039 and two subjects to placebo (3-to-1 ratio) for 28 days.

Secondary objectives are to correlate RG3039 PK with a panel of molecular biomarkers, and to determine the inhibitory plasma concentrations of RG3039 for the target enzyme DcpS.  It is the company’s expectation that cumulative Phase 1 study outcomes will inform the approach and design of a future efficacy study of RG3039 in SMA patients.

Phase 1a Results:

The initiation of this Phase 1b study follows on the completion by Repligen of a Phase 1a trial earlier this year.  The Phase 1a study was a blinded, ascending single dose study of RG3039 administered to 32 healthy volunteers.  Positive results from this single dose study were presented and the Annual Meeting of the American Academy of Neurology (AAN) in April 2012.  Those results demonstrated that RG3039 was well tolerated at plasma levels exceeding those in which cellular DcpS was fully inhibited.  The data showed evidence of a dose related drug exposure and target binding that resulted in greater than 90% inhibition of the target enzyme DcpS in peripheral blood cells for 48 hours.

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