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 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.
Top-line results from this Phase 1 study of RG3039 are scheduled to be
presented as part of a special neuroscience program at the 64th
Annual Meeting of the American Academy of Neurology (AAN). The AAN
meeting is being held April 21-28, 2012 at the New Orleans Ernest N.
Morial Convention Center. James P. Van Meerbeke, Research Assistant from
the lab of Charlotte J. Sumner, M.D., Associate Professor of Neurology
and Neuroscience, Johns Hopkins University School of Medicine, will
present the abstract titled “The Therapeutics Effects of RG3039 in
Severe Spinal Muscular Atrophy – Mice and Normal Human Volunteers,”
during “The Future of Neuroscience Conference: Neurologists and
Neuroscientists Defining the Next Generation of CNS Therapies,” taking
place on April 27.
In addition to the Phase 1 clinical trial outcomes, the AAN presentation
highlights the results of earlier mouse model studies conducted with
RG3039 at Johns Hopkins University and in the lab of Dr. Chien-Ping Ko
at University of Southern California. In these preclinical studies,
which provided proof of principle for conducting human clinical studies,
administration of RG3039 resulted in a significant improvement in
survival, increased maximum body weight and improved motor behavior in
severe SMA mice. The effects were associated with increased SMN2
transcript levels and improved neuromuscular junction morphology and
physiology.