EMERYVILLE, Calif.—West Coast-based Adamas Pharmaceuticals Inc. has taken its first steps toward aiding individuals afflicted with multiple sclerosis (MS) to walk faster and better. The company recently shared positive findings from its Phase 2 proof-of-concept study designed to evaluate ADS-5102 (amantadine HCl) extended-release capsules for the treatment of levodopa-induced dyskinesia associated with Parkinson’s disease and for the treatment of major symptoms associated with multiple sclerosis in patients with walking impairment.
The Phase 2 multicenter, randomized, double-blind, placebo-controlled, parallel group study evaluated ADS-5102 dosed at 340 mg once daily in an MS population for four weeks. Efficacy analyses were based on a modified intent-to-treat population (n=56). The primary outcome measure was the safety and tolerability of ADS-5102. Key secondary outcome measures included assessments of walking performance.
Data from the study indicate that ADS-5102 is well tolerated in the MS patient population and has a significant positive impact on walking speed, Adamas announced May 2. The data supports further clinical development of ADS-5102 in MS.
“We are excited by these positive MS walking data, which represent our fourth successful controlled clinical trial with ADS-5102,” states Gregory T. Went, chairman and CEO of Adamas. “We are now ready to speak with the FDA about a pivotal registration program for impaired walking in people with MS.”
“We believe these novel data show a benefit of ADS-5102 on walking speed in MS patients and the positive data generated in our Phase 3 trials for both dyskinesia and ‘off’ time in Parkinson’s patients with dyskinesia to further validate the strength of Adamas’ ‘shape matters’ discovery and development platform,” Went says. “The notion of shape incorporates aspects like timing, the profile and drug level and how they can be modified to improve the way medicines behave in the body.”
Dr. Rajiv Patni, chief medical officer of Adamas Pharmaceuticals, notes that approximately 75 percent of individuals with MS experience clinically significant walking impairment.
Currently there is no effective treatment or cure for MS. According to the National Institutes of Health, “multiple sclerosis (MS) can range from relatively benign to somewhat disabling to devastating, as communication between the brain and other parts of the body is disrupted. Many investigators believe MS to be an autoimmune disease—one in which the body, through its immune system, launches a defensive attack against its own tissues.” In multiple sclerosis, damage to the myelin in the central nervous system (CNS)—and to the nerve fibers themselves—interferes with the transmission of nerve signals between the brain and spinal cord and other parts of the body. In general, MS affects approximately 270,000 individuals in the United States. In a 2013 patient survey on MS in America, 76 percent of respondents reported walking difficulties.
Susan Lehner, senior director of corporate communications and investor relations at Adamas, told DDNews that ADS-5102 was developed by researchers at Adamas after “we started looking at the needs of patients impacted by chronic disorders of the central nervous system.”
“Specifically, we designed ADS-5102 to be given once daily at bedtime, to have a release profile which allows the medicine to gradually reach and then sustain peak therapeutic blood levels, starting first thing in the morning and extending throughout the day, and decreasing in the evening,” Lehner says. “Our data demonstrates that ADS-5102 provides patients with therapeutic benefit during their waking hours when it’s needed most.”
“To our knowledge, this is the only controlled clinical study that has evaluated the effects of amantadine on walking speed in the MS patient population,” she adds.
One measure used in this Phase 2 trial is the timed 25-foot walk (T25FW) test, Lehner says. This is a well-established outcome measure, one that has previously been used as a basis for product approval in the United States and Europe. In the trial, an approximately 15-percent placebo-adjusted improvement in walking speed was measured by the T25FW test, a statistically significant improvement, according to Lehner.
With the completion of the Phase 2 trial, “we turn our attention to finalizing our analysis, our briefing package and meeting with the FDA to discuss a plan for further clinical development of ADS-5102 for the treatment of walking impairment in patients with MS,” she explains.
The types of adverse events (AEs) reported with ADS-5102 in this study were consistent with the known safety profile of amantadine. The majority of study participants experienced at least one AE (17 patients in the ADS-5102 group and 19 patients in the placebo group). The recorded AE intensity was mild or moderate in the majority of patients (88 percent in the ADS-5102 group, 100 percent in the placebo group). Five patients discontinued study drug due to an AE.
Adamas plans to commercialize ADS-5102, and potentially other wholly owned product candidates, if approved, by developing a small CNS commercial organization, including a sales force targeting neurologists and movement disorder specialists in the United States, and possibly through distribution agreements and license agreements with CNS-focused pharmaceutical companies.
In addition, “we also expect to submit our first NDA for ADS-5102 in 2016 for levodopa-induced dyskinesia associated with Parkinson’s disease,” Went says. “Over the next several months, we intend to analyze the best additional opportunities for ADS-5102 to create new therapies where no medicines exist or where improved treatment options are needed.”