Osmotica Pharmaceuticals US LLC Submits Amended NDA for Arbaclofen Extended Release Tablets to U.S. Food and Drug Administration
-- Submission based on world’s largest database of patients treated for spasticity associated with Multiple Sclerosis --
-- Demonstrated efficacy, tolerability and one-year safety results on 80 mg/day --
“We are excited to have resubmitted our NDA for arbaclofen ER, our novel treatment, using the Osmodex technology, for MS spasticity. With the recent completion of our 12-month open-label study – assessing the long-term safety and tolerability of arbaclofen ER 80 mg/day - this resubmission also includes the full results of our second Phase 3 efficacy study (“OS440-3004”). The safety and efficacy results from these studies, together with the entire data package from our clinical development program, supports the clinical significance of arbaclofen ER as a potential treatment for MS spasticity. We look forward to working with the FDA during the course of its review,” stated
The arbaclofen ER clinical development program represents one of the largest clinical databases of placebo-controlled and open-label studies conducted in MS spasticity patients. The key primary efficacy assessment of spasticity for the pivotal studies was the generally accepted gold standard measure, Total Numeric modified Ashworth Scale TNmAS most affected limb (“TNmAS-MAL”). In addition, a co-primary measure, the Clinician Global Assessment of Change (“CGIC”) was examined to provide an assessment of patient’s general well-being. The compelling evidence provided by these studies clearly demonstrated clinically improved MS spasticity in patients administered arbaclofen ER in two, large three-month, placebo-controlled studies, and in two one-year, open-label safety studies.
Results of Study OS440-3004 revealed a statistically significant improvement from baseline to Day 84 in TNmAS-MAL scores in the arbaclofen ER tablet target dose of 40 mg/day (20 mg given twice a day) group compared to the placebo group. Subjects dosed with 80 mg/day (40 mg given twice a day) also derived significant clinical benefit. Though the mean Clinical Global Impression of Change score for arbaclofen ER was not significantly better than placebo, subjects treated with arbaclofen ER tablets did not show a mean worsening of CGIC scores after treatment.
The long-term open-label study OS440-3005 dosed subjects for up to one year on arbaclofen ER. The majority of subjects enrolled completed the study on the arbaclofen 80 mg/day dose. Of particular note, subjects dosed with arbaclofen ER up to 80 mg daily showed an overall improvement from baseline scores in the TNmAS measure up to one year demonstrating the durability of arbaclofen ERs efficacy. The drug was safe and generally well tolerated throughout the study.
“We are currently unaware of any MS spasticity program that has the breadth and scope in terms of long-term safety and tolerability assessments while demonstrating efficacy,” stated
Spasticity is one of the more common and disabling symptoms of MS. Spasticity in MS is a result of demyelination along the nerves of the brain and spinal cord that control movement. Certain muscles are continuously contracted, which causes stiffness and tightness of the muscles and/or a wide range of involuntary muscle spasms. The main feature of spasticity is stiffness or increased resistance when attempting to move a limb or joint. Often, spasticity can worsen at night with tight muscles and pain from symptoms making it difficult for patients to sleep. Current anti-spastic treatment options, such as baclofen and tizanidine, as well as others, offer limited clinical benefit due to tolerability concerns.
About Arbaclofen ER
Baclofen is a racemate (rac-baclofen) consisting of an equal mixture of two enantiomers: the
l- or R-enantiomer (arbaclofen) and the d- or S-enantiomer. Arbaclofen is the active R-enantiomer of baclofen, and the literature reveals convincing evidence that the efficacy of baclofen is primarily due to the R-enantiomer whereas the S-enantiomer may be inactive and may contribute to adverse events. In a pharmacokinetic/ pharmacodynamic study in healthy volunteers, R-baclofen plasma and cerebral spinal fluid concentrations following administration of immediate-release arbaclofen and baclofen were comparable. The observed increased propensity for drowsiness to occur after baclofen administration was attributed to the S-enantiomer of baclofen.
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