Repligen Corporation (NASDAQ:RGEN) today announced positive results from a Phase 1 study to evaluate the pharmacokinetic (PK) and safety profile of RG3039, a novel small molecule drug candidate for the potential treatment of spinal muscular atrophy (SMA). SMA is a inherited neurodegenerative disease in which symptoms of progressive damage to motor neurons including loss of muscle function typically appear very early in life and often progress to severe physical disability and early loss of life. The Phase 1 trial was a blinded, ascending, single dose study of RG3039 administered to 32 healthy volunteers. The study results demonstrate that RG3039 was well tolerated at all doses administered, with no serious adverse events reported. The data also showed evidence of a dose-related drug response resulting in 90% inhibition of the target enzyme. These outcomes may help to establish appropriate RG3039 dosing regimens for future studies, including potential efficacy studies in SMA patients.
“The agency has previously granted Orphan Drug and Fast Track designations to RG3039, in recognition of the unmet medical need that exists for patients with SMA and the urgency to advance a treatment for this devastating disease.”
"The safety and PK outcomes from our Phase 1 study of RG3039 are encouraging, and we look forward to initiating the next steps for this drug candidate in alignment with guidance from the U.S. Food and Drug Administration," said Walter C. Herlihy, President and Chief Executive Officer of Repligen. "The agency has previously granted Orphan Drug and Fast Track designations to RG3039, in recognition of the unmet medical need that exists for patients with SMA and the urgency to advance a treatment for this devastating disease."
Repligen licensed RG3039 in 2009 from Families of Spinal Muscular Atrophy (FSMA), a patient advocacy organization that 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. Repligen's research efforts including this Phase 1 study have been partially supported by a grant from the Muscular Dystrophy Association (MDA).
RG3039 is the first clinical-stage drug candidate to target the core genetic deficit in SMA in order to treat the biochemical deficits caused by decreased levels of the survival motor neuron (SMN) protein. This key protein is necessary for normal neuromuscular function but is insufficiently produced in SMA patients. 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.