-- Results presented in oral platform and poster sessions at the 69th American Academy of Neurology (AAN) Annual Meeting --
-- Results from the pooled analysis showed approximately twice as many ADS-5102 treated patients as placebo treated patients reported complete resolution of ON time with troublesome dyskinesia and OFF time at 12 weeks --
-- New Drug Application for ADS-5102 currently under FDA review with August 24, 2017, PDUFA date --
EMERYVILLE, Calif., April 24, 2017 (GLOBE NEWSWIRE) -- Adamas Pharmaceuticals, Inc. (Nasdaq:ADMS) today announced the presentation of two separate analyses of pooled data from the placebo-controlled Phase 3 clinical trials of ADS-5102 (amantadine) extended-release capsules in oral platform and poster presentation sessions at the 69th American Academy of Neurology (AAN) Annual Meeting in Boston. The pooled data results, which are consistent with the original findings from EASE LID and EASE LID 3, demonstrated that people with Parkinson's disease treated with ADS-5102 had a significant reduction in levodopa-induced dyskinesia (LID), as measured by the Unified Dyskinesia Ratings Scale (UDysRS), and showed statistically significant reduction in OFF time, as reported by Parkinson’s disease home diary data.
“Adamas is excited to present this important research at the AAN Annual Meeting,” stated Gregory T. Went, Ph.D., Chairman and Chief Executive Officer of Adamas Pharmaceuticals, Inc. “We continue to be highly-encouraged by the strength and consistency of the ADS-5102 data, as we believe it demonstrates that ADS-5102, if approved, has the potential to be an important new treatment for people with Parkinson’s disease. Given the upcoming PDUFA date for ADS-5102, our company is now at an important inflection point; we look forward to making this treatment available for patients and creating value for all Adamas shareholders.”
Oral Platform Presentation (Primary Endpoint)
Pooled Analysis of Phase 3 Studies of ADS-5102 (amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia: A Detailed Review of UDysRS Results
The UDysRS data from EASE LID and EASE LID 3 were pooled in a pre-specified analysis. The UDysRS included both physician assessments and historical patient assessments. The pooled ADS-5102 UDysRS results showed a significant, rapid and durable reduction in LID versus placebo:
- At Week 12, the UDysRS total score was -17.7 in the ADS-5102 group versus -7.6 in the placebo group (p<0.0001) – an improvement in the UDysRS total score of approximately 30 percent among those treated with ADS-5102 compared to placebo treated patients.
- For any change from baseline in UDysRS total score, a greater proportion of patients taking ADS-5102 showed a reduction compared to placebo.
- Treatment effects were comparable in both the objective (physician-assessed) and historical (patient-reported) UDysRS scores, and reductions were significantly greater with ADS-5102 than with placebo (p<0.0001 for both).
“The magnitude of the reduction of LID, as well as the significant reduction in OFF time, demonstrated with ADS-5102 treatment is an important advancement in the management of Parkinson’s disease,” said Rajesh Pahwa, M.D., Laverne & Joyce Rider Professor of Neurology and Director of the Parkinson's Disease and Movement Disorder Center at the University of Kansas Medical Center. “To my knowledge, ADS-5102 is the first and only medicine to provide both of these benefits to patients on levodopa therapy. As a result, patients treated with ADS-5102 in the Phase 3 studies gained approximately four hours of ON time without troublesome dyskinesia daily.”
Poster Presentation (Secondary Endpoints)
Pooled Analysis of Phase 3 Studies of ADS-5102 (amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia: A Detailed Review of PD Home Diary Results
Parkinson’s disease home diary data from the ADS-5102 Phase 3 EASE LID and EASE LID 3 studies were pooled to summarize the results of the secondary endpoints of ON time without troublesome dyskinesia, ON time with troublesome dyskinesia and OFF time. Results showed that patients treated with ADS-5102 reported a clinically meaningful increase in ON time without troublesome dyskinesia, due to significant reductions in both ON time with troublesome dyskinesia and OFF time, at 12 weeks compared to placebo:
- Treatment with ADS-5102 improved ON time without troublesome dyskinesia by approximately 40 percent compared to placebo (p<0.0001), which represents a 2.4 hour per day increase in ON time without troublesome dyskinesia.
- Treatment with ADS-5102 decreased OFF time by approximately 45 percent compared to placebo (p=0.0006), which represents a 1 hour per day decrease in OFF time.
- The treatment effect of ADS-5102 on OFF time was consistent across subgroups, including baseline OFF severity.
Additional analyses of the pooled Parkinson’s disease home diary data showed that among ADS-5102 treated patients, 52 percent reported complete resolution (0 hours) of ON time with troublesome dyskinesia compared to 23 percent of placebo treated patients. Also, these analyses showed that among ADS-5102 treated patients, 68 percent reported marked improvement (>2 hours) in ON time without troublesome dyskinesia compared to 40 percent of placebo treated patients.
“The pooled analysis of the key secondary endpoints, Parkinson’s disease home diary data from patients treated with ADS-5102, is consistent with the ADS-5102 primary UDysRS results and these complementary findings are clinically meaningful. Two of the most troublesome motor problems experienced by people with Parkinson’s disease – levodopa induced dyskinesia and OFF time – were both improved,” said Caroline M. Tanner, M.D., Ph.D., Director of the Parkinson's Disease Research, Education and Clinical Center at the San Francisco Veterans Affairs Medical Center and professor in residence in the Department of Neurology at the University of California, San Francisco. “Also, the additional analysis showing that more than half of Phase 3 study participants treated with ADS-5102 had complete resolution of ON time with troublesome dyskinesia, compared to fewer than one-fourth of those in the placebo group, is compelling.”
In the Phase 3 EASE LID and EASE LID 3 studies, the most common adverse events were consistent with the known amantadine safety profile, and most occurred between Weeks 2-4 of treatment. The majority (84 percent) of ADS-5102 treated patients did not discontinue study drug due to adverse reactions. The most common adverse reactions (≥5 percent in the active group) were visual hallucinations, dry mouth, dizziness, peripheral edema, falls, constipation, nausea, anxiety, decreased appetite, livedo reticularis, insomnia, auditory hallucinations and orthostatic hypotension.
About EASE LID and EASE LID 3
The randomized, double-blind, placebo-controlled, multi-center, ADS-5102 Phase 3 EASE LID and EASE LID 3 studies were of identical design except for a longer treatment duration in EASE LID. The two studies were designed to evaluate the safety and efficacy of 340 mg amantadine HCl doses of ADS-5102 taken once daily at bedtime -- for 25 weeks in EASE LID and 13 weeks in EASE LID 3 -- for the treatment of LID in people with Parkinson's disease. The primary efficacy endpoint for both studies was the change from baseline in the UDysRS total score at Week 12, which assessed the reduction in LID. Key secondary efficacy endpoints were changes from baseline in ON time without troublesome dyskinesia, OFF time, and ON time with troublesome dyskinesia at Week 12 (and Week 24 in EASE LID), as assessed by a standardized Parkinson’s disease home diary.
In accordance with the nomenclature naming guidance of the U.S. Pharmacopeia salt policy, potential labeling of ADS-5102 for the treatment of LID in people with Parkinson’s disease will refer to 274 mg amantadine (equivalent to 340 mg amantadine HCl) capsules, as the recommended daily dose. For reference, the equivalent quantity of amantadine contained in a 100 mg amantadine HCl immediate release tablets is 80.6 mg.
About ADS-5102
ADS-5102 is a high-dose amantadine, taken once daily at bedtime, in development for the treatment of levodopa-induced dyskinesia (LID) in people with Parkinson's disease. A New Drug Application (NDA) supporting ADS-5102 for the treatment of LID in people with Parkinson's disease is under review by the U.S. Food and Drug Administration (FDA), with a Prescription Drug User Fee Act (PDUFA) date of August 24, 2017. If approved, ADS-5102 will be the first and only FDA-approved medicine indicated for the treatment of LID in people with Parkinson's disease. Adamas is also investigating ADS-5102 for the treatment of walking impairment in people with multiple sclerosis and is considering developing it for other indications earlier in the Parkinson's disease treatment journey.
About Parkinson's Disease and Levodopa-induced Dyskinesia
Parkinson's disease is a chronic neurodegenerative disorder affecting close to 1 million people in the United States. It is characterized by the progressive loss of dopaminergic neurons, causing lower levels of endogenous dopamine and manifesting as symptoms of bradykinesia (slowness of movement), rigidity, impaired walking, tremor and postural instability.
Levodopa, which replaces lost dopamine, is the most effective therapy for all stages of Parkinson's disease and is considered the "gold standard" therapy. Over time, people require increasingly higher or more frequent doses of levodopa in order to avoid the recurrent periods of OFF time when the underlying symptoms of Parkinson’s disease return. As Parkinson’s disease progresses, nearly all people on levodopa therapy will also experience LID, which is characterized by involuntary movements that are non-rhythmic, purposeless and unpredictable. These people often experience multiple fluctuating periods of OFF time and LID during any given day, which can impede their movement and daily function. In the United States, approximately 150,000 to 200,000 people with Parkinson’s suffer from LID.
About Adamas Pharmaceuticals, Inc.
Adamas develops new medicines to improve the daily lives of those affected by chronic neurologic disorders, including Parkinson's disease, multiple sclerosis, epilepsy and Alzheimer's disease. Adamas has pioneered a platform to develop medicines, called chrono-synchronous therapies, for chronic neurologic disorders based on an understanding of the time-dependent biologic processes responsible for disease activity and drug response to potentially achieve symptomatic relief without tolerability issues. The company's most advanced product candidate, ADS-5102, is in development for levodopa-induced dyskinesia (LID) in people with Parkinson's disease and walking impairment in people with multiple sclerosis. An NDA supporting ADS-5102 for the treatment of LID in people with Parkinson's disease is under review by the FDA, with a PDUFA date of August 24, 2017. Adamas is exploring other indications for ADS-5102 for further development. Adamas is also investigating ADS-4101 for the treatment of partial onset seizures in patients with epilepsy. Additionally, Adamas’ licensed assets, are currently marketed by Allergan under the brand names NAMENDA XR® and NAMZARIC®, and Adamas is eligible to receive royalties on sales of these medicines beginning in June 2018 and May 2020, respectively. For more information, please visit www.adamaspharma.com.
NAMENDA XR® and NAMZARIC® are trademarks of Merz Pharma GmbH & Co. KGaA.
Forward-looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including but not limited to, statements contained in this press release regarding the potential approval of ADS-5102 for the treatment of levodopa-induced dyskinesia in people with Parkinson's disease and the potential clinical benefits of ADS-5102. Words such as "expect," "anticipate," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. For a description of risks and uncertainties that could cause actual results to differ from those expressed in forward-looking statements, including risks relating to Adamas' research, clinical, development and commercial activities relating to ADS-5102 and ADS-4101, the regulatory and competitive environment and Adamas' business in general, see Adamas' Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 28, 2017. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. Adamas undertakes no obligation to update any forward-looking statement in this press release.