Novel retrospective analysis of GOCOVRI® pooled Phase 3 Parkinson’s disease diary data, presented at the International Association of Parkinsonism and Related Disorders World Congress; June 16-19, 2019; Montreal, Canadaand published in the Journal of Parkinson’s Disease
EMERYVILLE, Calif., June 18, 2019 (GLOBE NEWSWIRE) -- Adamas Pharmaceuticals, Inc. (ADMS), a fully-integrated pharmaceutical company pioneering time-dependent medicines for central nervous system (CNS) disorders, today announced a retrospective data analysis from pooled Phase 3 trials of GOCOVRI® (amantadine) extended release capsules were presented at the International Association of Parkinsonism and Related Disorders (IAPRD) World Congress, and published in the Journal of Parkinson’s Disease, online 8th May 2019. The poster entitled, “Troublesome Dyskinesia and OFF Prevalence Throughout the Day: Population Profile and GOCOVRI® Effects on Frequency and Duration of These Episodes Relative to Placebo,” demonstrated that dyskinesia and OFF states occur erratically throughout the waking day in people with Parkinson’s disease, and that GOCOVRI® demonstrated a reduction in the number, duration, and transitions between episodes of troublesome dyskinesia and OFF experienced daily by patients.
GOCOVRI® is the first and only medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications. It is also the only medicine clinically proven to reduce both dyskinesia and OFF. In the pooled Phase 3 analysis, most adverse events were of mild to moderate intensity, and the most common (>10%) adverse events were hallucination, dizziness, dry mouth, peripheral edema, constipation, falls, and orthostatic hypotension.
“We often don’t realize the prevalence and unpredictability of these transitions from episodes of troublesome dyskinesia and OFF, and how they can disrupt a patient’s day and quality of life,” said Robert A. Hauser MD, MBA, Professor of Neurology and Director, USF Health Byrd Parkinson’s Disease and Movement Disorders Center Parkinson Foundation Center of Excellence, and lead author of the publication. “This retrospective data analysis provides a window into the true patterns of these episodes throughout the day and how GOCOVRI® can reduce both the number and duration of these episodes of troublesome dyskinesia and OFF, consistent with the data from GOCOVRI®’s Phase 3 clinical studies. To my knowledge, both of these observations have not been previously reported in Parkinson’s disease, and GOCOVRI® is the first product that is clinically proven to reduce both dyskinesia and OFF, resulting in longer periods of improved movement control.”
Participants in the GOCOVRI® pivotal Phase 3 trials filled out diaries documenting their motor state every 30 minutes over the course of a day, both at baseline and week 12 of the study. These data were used to map the daily patterns of dyskinesia and OFF episodes and evaluate the ability of GOCOVRI® to reduce the number and duration of these poor motor control states. Based on evaluable diary data from 162 patients, episodes of dyskinesia and OFF occur sporadically throughout the day, with patients experiencing, on average, just over eight transitions between episodes of OFF, Good ON, and troublesome dyskinesias. GOCOVRI® reduced both the number and duration of troublesome dyskinesia and OFF episodes relative to placebo, such that patients experienced approximately half as many transitions between troublesome dyskinesia and OFF at endpoint vs baseline. The duration of the first episode of the day on Good ON time increased by an average of 5.2 hours in the GOCOVRI® group, compared with 2.0 hours for placebo. Good ON time is defined as time spent in the ON state without experiencing troublesome dyskinesia.
“In the retrospective analysis of the diary data from our Phase 3 study, we see that GOCOVRI® significantly reduced both the number and duration of troublesome dyskinesia and OFF episodes relative to placebo, allowing patients to experience fewer and shorter episodes and increasing the duration of continuous Good ON time,” said Rajiv Patni, MD, Chief Medical Officer of Adamas Pharmaceuticals. “These data further reinforce our view that blocking the hyperactive glutamate system in a time-dependent manner is critical in managing these disabling symptoms throughout the waking day.”
About Parkinson’s Disease, OFF and Dyskinesia
Parkinson’s Disease (PD) is a progressive, neurodegenerative disorder caused by a dysregulation of neurotransmitter signaling, afflicting approximately one million people in the United States. The gradual loss of brain cells producing the neurotransmitter dopamine leads to this dysregulation, resulting in motor (movement related) and non-motor symptoms. The primary PD treatment approach is with levodopa, a dopamine precursor, that works by entering the brain and being converted to dopamine. While this replacement of dopamine is initially highly effective in relieving motor symptoms, over time, many patients develop a fluctuating, and unpredictable response to levodopa. At low dopamine levels, patients experience stiffness and rigidity, referred to as OFF periods, while at high dopamine levels they experience involuntary movements known as dyskinesia. The abrupt and unpredictable transitions between episodes of OFF, dyskinesia and normal movement (referred to as Good ON) lead to considerable disruption of patients’ lives. At this stage of the disease since the motor symptoms and underlying glutamate hyperactivity are thought to follow a diurnal pattern across the waking day of patients, a therapy that effectively attenuates glutamate hyperactivity using a time-dependent approach, may help improve good motor control throughout the waking day in individuals with dyskinesia and OFF.
About GOCOVRI® QHS
GOCOVRI® (amantadine) extended-release capsules is the first and only FDA-approved medicine indicated for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications. It is also the only medicine clinically proven to reduce both dyskinesia and OFF.
GOCOVRI® is thought to work by reducing the amount of glutamate hyperactivity in a region of the brain that controls movement, in patients experiencing dyskinesia and OFF. The NMDA receptor is activated by glutamate and causes post-synaptic nerve signaling in this area of the brain, which is modulated by dopamine. Levodopa therapy replaces dopamine lost in Parkinson’s disease, but may result in large fluctuations in synaptic levels of dopamine during waking hours, further exacerbating glutamate hyperactivity. GOCOVRI®, developed by Adamas, is novel in that it selectively blocks the NMDA receptor in a time-dependent manner. Taken at bedtime (QHS), GOCOVRI® provides an initial lag and a slow rise in amantadine concentration during the night and a high concentration from the morning and throughout the waking day. Additionally, adjunctive use of GOCOVRI® does not require dose changes to dopaminergic therapies. The most commonly observed adverse reactions with GOCOVRI® were hallucinations, dizziness, dry mouth, peripheral edema, constipation, fall and orthostatic hypotension.
For more information about GOCOVRI®, please see the U.S. Prescribing Information at www.GOCOVRI.com.
About Adamas Pharmaceuticals, Inc.
Adamas’ goal is to create and commercialize a new generation of medicines intended to lessen the burden of chronic neurologic diseases on patients, caregivers and society using its deep understanding of time-dependent biology. The company is focused on the commercialization of GOCOVRI® (amantadine) extended release capsules, the first and only FDA-approved medicine for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications. The Company also continues to deliver differentiated investigational programs, including ADS-5102 in development for the treatment of walking impairment in patients with multiple sclerosis. For more information about Adamas and its unique approach to developing medicines based on time-dependent biology, please visit www.adamaspharma.com.
Important Safety Information
Before taking GOCOVRI®, patients should tell their doctor about all medical conditions, including if they:
- Have kidney problems; unexpected sleepiness; take medicine to help them sleep or that makes them drowsy; have mental problems, such as suicidal thoughts, depression, or hallucinations; unusual urges including gambling, increased sex drive, compulsive eating, or shopping; or if they drink alcoholic beverages.
- Are pregnant or plan to become pregnant or are breastfeeding or plan to breastfeed. GOCOVRI® may harm the unborn baby and can pass into breastmilk.
Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements, especially if medicines like sodium bicarbonate are taken.
What should patients avoid while taking GOCOVRI®? Patients should NOT:
- Take GOCOVRI® if they have severe kidney problems.
- Drive, operate machinery, or do other dangerous activities until they know how GOCOVRI® affects them.
- Drink alcohol while taking GOCOVRI® as it can increase their chances of serious side effects.
- Stop or change the dose of GOCOVRI® before talking with their doctor.
- Take a flu nasal spray vaccine while taking GOCOVRI®, but they can receive a flu shot.
What are the possible side effects of GOCOVRI?
GOCOVRI may cause serious side effects, including:
- Falling asleep during normal activities, such as driving, talking, or eating, while taking GOCOVRI®. Patients may fall asleep without being drowsy or warning.
- Suicidal thoughts or actions and depression.
- Occurrence or worsening of hallucinations (seeing or hearing things that are not real).
- Feeling dizzy, faint or light headed, especially when standing up too quickly, when first starting GOCOVRI®, or if a patient’s dose has been increased.
- Unusual urges including gambling, sexual, spending money, binge eating, and the inability to control them.
If a patient or their family notices that they are developing any new, unusual or sudden changes in behavior or related symptoms, inform the patient’s healthcare provider right away.
The most common side effects of GOCOVRI® include dry mouth, swelling of legs and feet, constipation, and falls.
For additional important safety information, please see GOCOVRI® full Prescribing Information at www.gocovri.com.
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