Third Randomized Clinical Trial Meets Primary and Key Secondary Endpoints
Conference Call and Webcast Today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time)
EMERYVILLE, Calif., April 28, 2016 (GLOBE NEWSWIRE) -- Adamas Pharmaceuticals, Inc. (Nasdaq:ADMS) today announced that its Phase 3 trial (EASE LID 3) evaluating ADS-5102 (amantadine HCl) extended-release capsules for the treatment of levodopa-induced dyskinesia (LID) associated with Parkinson’s disease (PD) met its primary and key secondary endpoints. Results from this randomized, double-blind, placebo-controlled study showed a statistically significant improvement (p<0.0001) in LID at 12 weeks (primary endpoint) for patients who received ADS-5102 versus placebo as assessed by the Unified Dyskinesia Rating Scale (UDysRS). Additionally, a statistically significant increase in ON time without troublesome LID (p=0.0168) and a statistically significant decrease in OFF time (p=0.0199) versus placebo, both key secondary endpoints, were observed. The company plans to present the data at an upcoming scientific conference.
“We are thrilled by the data resulting from EASE LID 3, our third randomized clinical study of ADS-5102 to have met its primary endpoint and show a statistically significant improvement in LID,” stated Gregory T. Went, Ph.D., Chairman and Chief Executive Officer of Adamas Pharmaceuticals, Inc. “We are pleased to see data from all three studies in LID that suggest ADS-5102 is the first investigational therapy with the potential to positively affect both dyskinesia and OFF time. We are excited about the possible role ADS-5102 may have in helping people with Parkinson’s disease, and we look forward to submitting a new drug application (NDA) to the FDA this year.”
“The uncontrollable involuntary movements associated with LID can be disruptive and debilitating for those living with Parkinson’s disease,” stated Joseph Jankovic, M.D., Professor of Neurology, Distinguished Chair in Movement Disorders and Director of the Parkinson Disease Center and Movement Disorders Clinic at the Baylor College of Medicine in Houston, Texas. “It is very encouraging to see that ADS-5102 has shown a reduction in LID across three clinical studies as well as a decrease in OFF time in two clinical studies.”
In the EASE LID 3 study, 77 PD patients with LID were randomized to placebo or active treatment (340 mg ADS-5102). Efficacy analyses were based on a modified intent-to-treat population of 75 patients. The treatment groups were similar with respect to baseline demographics and PD-related medical history. Data are summarized below:
Primary Endpoint (UDysRS)
- The percent reduction from the observed mean UDysRS total score at baseline compared to that at week 12 was 50 percent in the ADS-5102 group and 18 percent in the placebo group. The least square (LS) mean treatment difference at week 12 was statistically significant (p<0.0001, primary endpoint).
Secondary Endpoints
PD Home Diaries
- ON time without troublesome dyskinesia increased by 4.0 hours per day in the ADS-5102 group and 2.1 hours per day in the placebo group (p=0.0168, key secondary endpoint).
- OFF time decreased by 0.5 hours per day in the ADS-5102 group and increased by 0.6 hours per day in the placebo group (p=0.0199, key secondary endpoint).
- ON time with troublesome dyskinesia decreased by 3.6 hours per day in the ADS-5102 group and 2.5 hours per day in the placebo group (p=0.0853).
Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)
- A statistically significant reduction (p<0.0001) in the MDS-UPDRS (Part IV) score was seen in the ADS-5102 group versus the placebo group.
- The effect of ADS-5102 was achieved without worsening the underlying PD as assessed by MDS-UPDRS (combined Parts I, II and III).
Safety Information
The types of adverse events (AEs) reported with ADS-5102 were consistent with the known safety profile of amantadine as well as safety results from the earlier randomized studies (EASED and EASE LID). Most patients experienced at least one AE (84 percent of the ADS-5102 group and 50 percent of the placebo group). For the majority of patients, the reported AEs were mild to moderate in intensity (70 percent of ADS-5102 patients, 45 percent of placebo patients). Four patients, all in the ADS-5102 group, experienced serious AEs, which were considered related to study drug in one patient. There were seven patients who experienced severe AEs, five patients in the ADS-5102 group and two in the placebo group. Ten patients discontinued study treatment due to an AE, seven patients in the ADS-5102 group and three in the placebo group.
The most common AEs (occurring in greater than two patients in the ADS-5102 group) were: dry mouth, nausea, decreased appetite, insomnia, orthostatic hypotension, constipation and visual hallucinations. Visual hallucinations were reported by three patients in the ADS-5102 group and by two in the placebo group. Of these, two patients in the ADS-5102 group discontinued study treatment.
Conference Call and Webcast Today, April 28, at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time)
The Adamas management team will host a conference call and webcast at 8:00 a.m. ET/ 5:00 a.m. PT on Thursday, April 28 to discuss the study results. Interested parties may access the webcast on the Adamas website at http://ir.adamaspharma.com/events.cfm, or by dialing 844-215-3280 (domestic) or 484-747-6383 (international) and referencing conference ID 2778439. A replay of the call will be available on the Adamas website later in the day. The replay will be available for approximately one month following the call.
About EASE LID 3
The Phase 3 EASE LID 3 study, which enrolled 77 patients at 39 sites located in the United States, Germany, France, Spain and Austria, was a multi-center, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of 340 mg of ADS-5102 dosed once daily at bedtime for 12 weeks in patients with LID associated with PD. The study's primary efficacy analysis measured the reduction in LID over 12 weeks as assessed by the UDysRS. Key secondary efficacy outcome measures were changes in a standardized PD home diary, including ON time without troublesome dyskinesia and OFF time at week 12. Other secondary efficacy outcome measures included ON time with troublesome dyskinesia based on PD home diaries, overall PD clinical status as assessed by the MDS-UPDRS and the Clinician’s Global Impression of Change.
ADS-5102 Phase 3 Program Overview
Adamas’ Phase 3 clinical program of ADS-5102 for the treatment of LID comprises three placebo-controlled trials: EASED, EASE LID and EASE LID 3. EASED, EASE LID and EASE LID 3 enrolled a total of 286 patients, of which 122 patients received a 340 mg dose of ADS-5102 once daily before bedtime for a prespecified period of time. In all three trials, a statistically significant reduction in LID versus placebo was achieved at each trial’s predefined treatment period as assessed by the UDysRS: week 8 (EASED), week 12 and week 24 (EASE LID) and week 12 (EASE LID 3). The types of AEs associated with ADS-5102 in the three completed trials were consistent with the known safety profile of amantadine. EASE LID 2, an open-label safety study that is open to patients from EASED, EASE LID and EASE LID 3 and to LID patients who have undergone deep brain stimulation, is ongoing. The company expects to submit a new drug application in 2016 and, assuming FDA approval, launch the product in 2017.
About ADS-5102
Adamas' most advanced wholly owned product candidate is ADS-5102 (amantadine HCl), an extended-release version of amantadine that is intended for once daily administration at bedtime. ADS-5102 is designed to improve upon the pharmacokinetic (PK) profile of immediate-release amantadine, with the aim of enhancing efficacy without compromising the known tolerability profile. In PK studies, ADS-5102 has been shown to achieve high plasma amantadine concentrations in the early morning that are sustained throughout the afternoon and are lower in the evening.
Parkinson's Disease and Levodopa-induced Dyskinesia
Parkinson's disease is a chronic, progressive motor disorder that causes a variety of symptoms, such as tremors, rigidity, slowed movements and postural instability. The most commonly prescribed treatments for Parkinson's disease are levodopa-based therapies. In the body, levodopa is converted to dopamine to replace the dopamine loss caused by the disease. Patients initially receive relief from symptoms of Parkinson's disease for much of the day. This period of relief is known as ON time. As the effects of levodopa wear off, the symptoms of Parkinson's disease return. This is known as OFF time.
As Parkinson's disease progresses, most patients require increasing doses of levodopa to achieve equivalent therapeutic benefit. Patients may also experience symptoms of their disease upon waking, prior to the first dose of levodopa taking effect. Over time many patients will suffer from levodopa-induced dyskinesia (LID), a condition characterized by involuntary movements without purpose. As Parkinson's disease advances, the symptoms of LID often worsen in frequency and severity. Eventually the total time that a patient spends ON with LID can become a significant portion of his or her day.
About Adamas Pharmaceuticals
Adamas Pharmaceuticals, Inc. is driven to improve the lives of those affected by chronic disorders of the central nervous system. The company seeks to achieve this by modifying the pharmacokinetic profiles of approved drugs to create novel therapeutics for use alone and in fixed-dose combination products. Adamas is currently developing ADS-5102, its lead wholly owned product candidate, 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 company is also evaluating ADS-4101, an extended-release version of a FDA-approved single-agent compound for the treatment of epilepsy. In addition, under a license agreement with Forest Laboratories Holdings Limited, an indirect wholly owned subsidiary of Allergan plc., the company is eligible to receive royalties from Forest on sales of Namenda XR® and Namzaric™ beginning in June of 2018 and May of 2020, respectively. For more information, please visit www.adamaspharma.com.
Namzaric™ is a trademark of Merz Pharma GmbH & Co. KGaA.
Namenda XR® is a registered trademark of Merz Pharma GmbH & Co. KGaA.
The statements contained in this press release that are not historical facts, including statements regarding Adamas’ expectations of presenting the results of the EASE LID 3 at an upcoming scientific conference, submitting a new drug application in 2016 and, assuming FDA approval, launching the product in 2017, are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. 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 the risks and uncertainties that could cause actual results to differ from those expressed in forward-looking statements, including risks relating to the FDA’s interpretation and review of the ADS-5102 data and program, ongoing research, clinical and development activities of ADS-5102, the regulatory and competitive environment, as well as risks relating to Adamas’ business in general, see Adamas’ Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 23, 2016. 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.