Adamas Pharma (ADMS) Reports Second ADS-5102 Phase 3 Met Primary Endpoint in PD

September 20, 2016 4:13 PM EDT
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Adamas Pharmaceuticals, Inc. (Nasdaq: ADMS) announced the results of the EASE LID 3 study, the second Phase 3 trial of ADS-5102 (amantadine hydrochloride) extended-release capsules for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease (PD). The trial met its primary endpoint, the reduction of the UDysRS (Unified Dyskinesia Rating Scale) total score at week 12 (p<0.0001), reflecting a decrease in the duration, intensity and disability associated with LID. In addition, a statistically significant reduction in OFF time (a key secondary endpoint) was observed, as measured by patient reported home diaries. A separate post hoc analysis of data from the EASE LID trial was also announced, reporting the impact LID has on activities of daily living (ADLs) of PD patients as well as the favorable effects of ADS-5102 on these ADLs. These data will be presented in two posters at the 4th World Parkinson Congress (WPC) in Portland, Oregon on September 20-23, 2016.

“Data from the EASE LID 3 trial of ADS-5102 further illustrates the potential for ADS-5102 to reduce the unwanted involuntary movements called dyskinesia, as well as OFF time, so patients can be more independent in their daily activities,” stated 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.

“We look forward to submitting a new drug application for ADS-5102 to the FDA later this year and the potential of bringing the first FDA-approved medicine for the treatment of LID to Parkinson’s patients in the coming year,” said Rajiv Patni, M.D., Adamas’ Chief Medical Officer.

Results of a Phase 3 Efficacy and Safety Study of ADS-5102 (amantadine hydrochloride) Extended-Release Capsules in Parkinson’s Disease Patients with Levodopa-induced Dyskinesia (EASE LID 3); Abstract 1331, Poster Board Number P35.20 – Selected for WPC Organized Poster Tour

This is the first scientific presentation of the EASE LID 3 trial evaluating ADS-5102 for the treatment of LID associated with PD. The trial met its primary endpoint and key secondary endpoints:

  • Primary Endpoint: ADS-5102 significantly decreased the UDysRS total score at week 12 compared with placebo. The percent reduction from the mean UDysRS total score at baseline compared to that at week 12 was 46 percent in the ADS-5102 group and 16 percent in the placebo group. Improvement in LID was evident at the first post-baseline UDysRS assessment at week 2 and was maintained through week 12.
  • Key Secondary Endpoints (PD Home Diaries): ADS-5102 increased ON time without troublesome dyskinesia by 1.9 hours per day, placebo adjusted (p=0.0168). In addition, OFF time decreased by 1.1 hours per day (p=0.0199).

ADS-5102 was generally well tolerated and the types of adverse events (AEs) reported were consistent with the known safety profile of amantadine. The most common adverse events occurring in more than five percent of subjects were dry mouth, nausea, decreased appetite, insomnia, orthostatic hypertension, fall and visual hallucination. One trial subject reported two study drug related serious adverse events, but the subject stayed on study drug and completed the trial.

ADS-5102 (amantadine hydrochloride) Extended-Release Capsules Improves Activities of Daily Living (ADLs) in Parkinson’s Disease (PD) Patients by Reducing Levodopa-induced Dyskinesia: A Post-Hoc Analysis from the Phase 3 EASE LID study; Abstract 1233; Poster Board Number P35.15

An analysis of the UDysRS data from the EASE LID pivotal Phase 3 trial was conducted to characterize the effect dyskinesia has on ADLs for patients with PD and to evaluate the treatment impact of ADS-5102 on ADLs. The analysis included patient reported data from Part 1B of the UDysRS.

The baseline data illustrate the major impact that dyskinesia has on the daily life of patients with Parkinson’s disease. Seventy percent of patients reported mild to moderate impairment of activities in ‘public and social settings’ as well as in ‘walking and balance’ at baseline.

Further analysis revealed that patients treated with ADS-5102 recorded a 7.0 point reduction from baseline in the UDysRS, Part 1B total score, compared to a 4.0 reduction for placebo. ADS-5102 was generally well tolerated and the types of AEs reported were consistent with the known safety profile of amantadine.

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. These trials enrolled a total of 286 patients, of whom 122 patients received a 340 mg dose of ADS-5102 once daily before bedtime. In all three trials, change in LID versus placebo was achieved at each trial’s predefined treatment period as assessed by the Unified Dyskinesia Rating Scale (UDysRS): change from baseline to week 8 (EASED), week 12 and week 24 (EASE LID) and week 12 (EASE LID 3). EASE LID 2 is an open-label safety study for patients from EASED, EASE LID and EASE LID 3 and for LID patients who have undergone deep brain stimulation. The EASE LID 2 trial is ongoing and patients will be followed for up to two years.

About ADS-5102 Adamas' most advanced wholly-owned product candidate is ADS-5102 (amantadine HCI) extended release capsules 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 hyperkinetic, involuntary, random movements often described as non-rhythmic, purposeless, and unpredictable. Dyskinesia is sometimes not recognized or difficult to differentiate from tremor. 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.

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