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

Elk Grove Village, IL. September 26, 2012.

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.

RG3039 is an orally bioavailable small molecule inhibitor of an RNA processing enzyme called DcpS.  RG3039 has been shown to increase production of the SMN protein in cells derived from patients.  In addition, RG3039 has been shown to improve motor neuron pathology, mobility and lifespan in animal models of SMA.

“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 Walter C. Herlihy, Ph.D., President and Chief Executive Officer of Repligen.  “We appreciate the support of our collaborators in conducting this Phase 1b trial and look forward to sharing the results.”

FSMA began the Quinazoline/RG3039 program in 2000 at the very initial stages of drug development, when risk is the highest.  It was the very first industrial drug program for SMA ever conducted.  The direction from FSMA provided the positive results necessary to license the program to Repligen Corporation and leverage larger funding for clinical development.

Click here to see more details about the program.

Click here to read about the groundbreaking licensing agreement.

About Families of Spinal Muscular Atrophy

Families of SMA funds and directs the leading SMA research programs to develop a treatment and cure for the disease.  The successful results and progress that the organization has delivered, from basic research to drug discovery to clinical trials, provide real hope for families and patients impacted by the disease. The charity has invested over $50 million in research and been involved in funding half of all the ongoing novel drug programs for SMA.  Families of SMA is a nonprofit 501(c)3 organization, with 31 Chapters and 85,000 members and supporters throughout the United States, and is dedicated to creating a treatment and cure by: funding and advancing a comprehensive research program; supporting SMA families through networking, information and services; improving care for all SMA patients; educating healthcare professionals and the public about SMA; enlisting government support for SMA; embracing all touched by SMA in a caring community. 

About Repligen Corporation

Repligen Corporation is a life sciences company focused on the development, production and commercialization of products used in the process of manufacturing biological drugs.  In addition to its core bioprocessing business, Repligen has developed a portfolio of clinical-stage drug candidate assets available for partnering, including RG3039 for the potential treatment of spinal muscular atrophy (SMA). For more information, please visit Repligen’s website at www.repligen.com.

Please contact Kenneth Hobby at Kenneth@fsma.org or call 1-800-886-1762 if you have any questions.

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