Anti-dyskinetic Effect Consistent Across Primary and Secondary Outcome Measures
EMERYVILLE, Calif., April 19, 2016 (GLOBE NEWSWIRE) -- Adamas Pharmaceuticals, Inc. (Nasdaq:ADMS) today announced positive findings from its lead Phase 3 study (EASE LID) evaluating ADS-5102 (amantadine HCl) extended-release capsules for the treatment of levodopa-induced dyskinesia (LID) associated with Parkinson’s disease (PD). Results from this randomized, double-blind, placebo-controlled study showed a statistically significant improvement (p = 0.0009) in LID at 12 weeks for patients who received ADS-5102 versus placebo as assessed by the Unified Dyskinesia Rating Scale (UDysRS). The improvement in LID was maintained at 24 weeks (p = 0.0008), a key secondary analysis. An anti-dyskinetic effect achieved by ADS-5102 was also demonstrated across multiple outcome measures, providing further data suggestive of a clinically meaningful benefit. These results (Emerging Science abstract # 014) were presented at the 68th American Academy of Neurology Annual Meeting in Vancouver, Canada.
“These findings support our upcoming new drug application for ADS-5102 for the treatment of LID associated with Parkinson’s disease, a motor complication for which there is currently no FDA-approved drug therapy,” stated Rajiv Patni, M.D., Chief Medical Officer of Adamas Pharmaceuticals. “The full treatment effect was seen at week 2, the first post-baseline efficacy assessment, and was durable out to six months. We are encouraged by the consistent improvement in LID seen across the Phase 2/3 EASED study and this Phase 3 EASE LID study. We look forward to presenting the results from our third controlled study, EASE LID 3, and the EASE LID 2 open-label safety study later this year.”
“LID is often a dose-limiting consequence of levodopa use and its treatment is a major unmet need for people with Parkinson’s disease,” stated Rajesh Pahwa, M.D., Laverne & Joyce Rider Professor of Neurology, Director of the Parkinson's Disease and Movement Disorder Center at the University of Kansas Medical Center. “LID limits our use of levodopa to treat the underlying symptoms of PD, like OFF episodes, and can have a detrimental impact on the lives of those faced with this debilitating side effect.”
About EASE LID
The Phase 3 EASE LID study 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 24 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. The key secondary efficacy outcome measures were a reduction in LID over 24 weeks as assessed by the UDysRS and changes in a standardized PD home diary, including ON time without troublesome dyskinesia and OFF time at weeks 12 and 24. Additional secondary efficacy outcome measures included overall PD clinical status as assessed by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Clinician's Global Impression of Change.
Three outcome measures were used to evaluate the therapeutic effect of ADS-5102 on LID: the UDysRS, PD home diaries and the MDS-UPDRS, Part IV. The following analyses were based on a modified intent to treat population of 121 Parkinson's disease patients with LID. The treatment groups were similar with respect to baseline demographics and Parkinson's disease-related medical history. Data are summarized below:
- The percent reduction from the observed mean UDysRS total score at baseline compared to that at week 12 was 42 percent in the ADS-5102 group and 19 percent in the placebo group. The least square (LS) mean treatment difference at week 12 was statistically significant (p = 0.0009, primary endpoint).
- Similarly, the percent reduction in observed mean UDysRS total score from baseline to week 24 was 40 percent in the ADS-5102 group and 16 percent in the placebo group. The LS mean treatment difference at week 24 was statistically significant (p = 0.0008).
PD Home Diaries
- At week 12, ON time with troublesome dyskinesia decreased by 3.2 hours in the ADS-5102 group and 1.6 hours in the placebo group (p = 0.0027). At week 24, ON time with troublesome dyskinesia decreased by 3.3 hours in the ADS-5102 group and 1.9 hours in the placebo group (p = 0.0072).
- At week 12, OFF time decreased by 0.6 hours in the ADS-5102 group and increased by 0.3 hours in the placebo group (p = 0.0170). At week 24, OFF time decreased by 0.6 hours in the ADS-5102 group and increased by 0.2 hours in the placebo group (p = 0.0406).
- At week 12, ON time without troublesome dyskinesia increased by 3.6 hours in the ADS-5102 group and 0.9 hours in the placebo group (p < 0.0001). At week 24, ON time without troublesome dyskinesia increased by 3.6 hours in the ADS-5102 group and 1.4 hours in the placebo group (p = 0.0007).
- A synchronized treatment group time profile of patients with evaluable diary sets at baseline and week 24 showed that ADS-5102 treatment increased ON time without troublesome dyskinesia by decreasing both ON time with troublesome dyskinesia and OFF time throughout waking hours.
MDS-UPDRS, Part IV
- At week 12 and week 24, a statistically significant reduction (p = 0.0005 and p = 0.0012, respectively) 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).
The reported adverse events (AEs) associated with ADS-5102 were consistent with the known safety profile of amantadine as well as safety results from the Phase 2/3 placebo-controlled study (EASED). There was one death in the study. The subject, who was in the ADS-5102 treatment group, died of advanced PD while in hospice; the death was deemed to be unrelated to study drug. Most subjects experienced at least one AE (89 percent of the ADS-5102 group and 60 percent of the placebo group). For the majority of subjects, the highest intensity for a reported AE was mild to moderate (68 percent of ADS-5102 subjects, 53 percent of placebo subjects). Ten subjects experienced serious AEs (SAEs), seven in the ADS-5102 group and three in the placebo group; none of the SAEs were considered related to study drug. There were 17 subjects who experienced severe AEs, 13 subjects in the ADS-5102 group and four in the placebo group. Seventeen subjects discontinued study treatment due to an AE, 13 subjects in the ADS-5102 group versus four in the placebo group. The most common AEs (occurring in greater than five percent of ADS-5102-treated patients) were: visual hallucinations, peripheral edema, dizziness, dry mouth, constipation, falls, urinary tract infections, anxiety, contusion, livedo reticularis, auditory hallucinations, abnormal dreams, depression and headaches. Onset of visual hallucinations typically occurred during the first month of treatment. Five of the 15 subjects in the ADS-5102 group who experienced visual hallucinations discontinued study drug due to this AE.
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 and EASE LID enrolled a total of 209 patients, of which 84 patients received a 340 mg dose of ADS-5102 once daily before bedtime for a prespecified period of time. In both 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) and week 12 and week 24 (EASE LID). The AEs associated with ADS-5102 in the two completed trials were consistent with the known safety profile of amantadine. EASE LID 3 is ongoing and fully enrolled with 77 patients. Additionally, Adamas is continuing to conduct EASE LID 2, an open-label safety study, which is open to patients from EASED, EASE LID, EASE LID 3 and LID patients who have undergone deep brain stimulation. The company expects to submit a new drug application in 2016 and, pending a positive review, launch the product in 2017 with its own targeted sales force.
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. The company's portfolio includes Namzaric™ and Namenda XR®, two approved products with Forest Laboratories Holdings Limited, an indirect wholly owned subsidiary of Allergan plc. Forest is responsible for marketing both products in the United States under an exclusive license from Adamas. 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 regarding Adamas’ expectations of presenting the results from its third controlled study, EASE LID 3, and the EASE LID 2 open-label study later this year, that Adamas expects to submit a new drug application in 2016 and, pending a positive review, launch the product in 2017 with its own targeted sales force, and statements regarding the potential for ADS-5102 for the treatment of LID, 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’ 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.
For questions, please contact: Susan Lehner Corporate Communications & Investor Relations Adamas Pharmaceuticals, Inc. Phone: 510-450-3567
Source:Adamas Pharmaceuticals, Inc.