Efficacy

Efficacy and safety profile demonstrated by a robust clinical program

THE EFFICACY AND SAFETY OF GOCOVRI® 274 mg QHS WERE EVALUATED IN 2 PHASE 3, RANDOMIZED, PLACEBO-CONTROLLED TRIALS1-3:

Study 11
24 weeks, n = 121
Study 22
13 weeks, n = 75
Study design
  • Phase 3 randomized, placebo-controlled
  • 274 mg GOCOVRI®, QHS
  • Baseline PD medications including levodopa were held constant
Primary endpoint
  • Change in UDysRS total score from baseline to week 12
Secondary endpoint
  • PD motor diary
  • Change in ON time without troublesome dyskinesia from BL to week 12
  • Change in OFF time from BL to week 12
Long-term open-label study3
100 weeks, N = 223
  • Open-label
  • 274 mg GOCOVRI®, QHS
  • Adjustments to BL PD medications including levodopa were allowed
  • Evaluated long-term safety, tolerability, and efficacy
BL, baseline; UDysRS, Unified Dyskinesia Rating Scale.
Primary endpoint

GOCOVRI® reduced dyskinesia without adjustments to existing levodopa or other dopaminergic therapies4

POOLED RESULTS: MEAN IMPROVEMENT IN UDysRS TOTAL SCORE AT WEEK 12 (MEAN BASELINE, 40.1)4

27% Mean Improvement in UDysRS Total Score at Week 12, Chart
* Percent improvement from baseline calculated using MMRM statistics model.4
  LS, least squares; MMRM, mixed model repeated measure; SE, standard error.
GOCOVRI® achieved a 10.1-point reduction in UDysRS (placebo-adjusted)4
Secondary endpoint6

Derived from patient diary data

GOCOVRI® reduced OFF time without adjustments to existing levodopa or other dopaminergic therapies4

POOLED RESULTS: MEAN REDUCTION IN OFF TIME AT WEEK 12 (MEAN BASELINE OF ALL PATIENTS: 2.8 HOURS)4,5

36% Mean Reduction in OFF Time at Week 12, Chart
GOCOVRI® decreased OFF time by 1 hour (placebo-adjusted)4
Secondary endpoint6

Derived from patient diary data

GOCOVRI® increased GOOD ON time without adjustments to existing levodopa or other dopaminergic therapies4

POOLED RESULTS: MEAN INCREASE IN GOOD ON TIME AT WEEK 12 (MEAN BASELINE OF ALL PATIENTS: 8.4 HOURS)4,5

29% Mean Increase in Good ON Time at Week 12, Chart

GOOD ON time = ON time without troublesome dyskinesia.

GOCOVRI® increased GOOD ON time by 2.4 hours (placebo-adjusted)4

Less dyskinesia and OFF time means more GOOD ON time throughout the waking day4

POOLED PATIENT DIARY RESULTS FROM STUDIES 1 AND 2 (AT 12 WEEKS)5

GOOD On Placebo Patients vs. GOCOVRI Patients at 12 Weeks
* Dyskinesia defined as ON time with troublesome dyskinesia.
GOOD ON time = ON time without troublesome dyskinesia.
Pooled baseline values (hours) for dyskinesia, OFF time, and GOOD ON time, respectively:
Placebo: 5.2, 2.6, and 8.1, GOCOVRI®: 4.7, 3.1, and 8.55

Results from a post-hoc analysis of the patient diary data

Exploring whether reductions in daily episodes increased continuous GOOD ON time7

POST-HOC ANALYSIS USING DIARY DATA EXPLORED THE CONNECTION BETWEEN REDUCING TRANSITIONS AND INCREASING CONTINUOUS GOOD ON TIME7*

SAMPLE DIARY PLOT FOR A SINGLE PATIENT THROUGHOUT THE WAKING DAY7

Sample Diary Plot
Adapted from Hauser, et al.
Swipe for more >
* Dyskinesia defined as ON time with troublesome dyskinesia.
GOOD ON time = ON time without troublesome dyskinesia.
Using diary plots as depicted above, the 162 evaluable patient diaries were combined to create the graphical representation below.7

ANALYSIS OF PATIENT DIARY PLOTS (n = 162) REPRESENTING 1 DAY AT BASELINE AND WEEK 127*

Patient Diary Plots of GOCOVRI® vs Placebo Post-hoc Analysis at 12 Weeks Displaying GOOD ON Time
Patient Diary Plots of GOCOVRI® vs Placebo Post-hoc Analysis at 12 Weeks Displaying GOOD ON Time
Slide bar to left and right

Week 12 Analysis of Motor State Episodes†

In patients receiving GOCOVRI®:

  • 57.1% reported no episodes of dyskinesia (vs 24.7% with placebo)
  • 27.3% reported no OFF time (vs 20.0% with placebo)
  • 19.5% reported no dyskinesia nor OFF time (vs 3.5% with placebo)
Patient Diary Analysis legend. Categories: Asleep, OFF Time, Dyskinesia, and GOOD ON Time
Adapted from Hauser, et al.
* Patients are organized in descending order of number of episodes reported at Week 12 (with baseline reordered to match, so that patient order is the same at baseline and Week 12).7
† Episodes are defined as time spent in a PD diary motor state (dyskinesia or OFF time) before entering another state.

A retrospective, subgroup analysis of patient diary data7:

  • Included only patients with baseline and Week 12 diaries (n = 162/196)
  • Evaluated the frequency, prevalence, and duration of episodes of troublesome dyskinesia and OFF time
  • Analyzed the effect of GOCOVRI® on these episodes
    • Episodes are defined as time spent in a PD diary motor state (dyskinesia or OFF time) before entering another state

Limitations of this analysis7:

  • Only analyzed preexisting data derived from a population with at least mild dyskinesia at baseline
  • Did not include patients who withdrew from the study prematurely
  • Did not include tools for capturing the intensity of clinical states

Due to these limitations, this analysis may not be applicable to a more generalized PD population, and no formal conclusions can be drawn.

In the EASE LID 2 open-label extension (OLE) study

GOCOVRI® long-term efficacy and safety were studied through 2 years3

REDUCTIONS IN DYSKINESIA AND OFF TIME (MDS-UPDRS Part IV) WERE ACHIEVED BY ALL TREATMENT GROUPS, REGARDLESS OF PREVIOUS THERAPY3

EASE-LID 2 Open-Label 100 Extension Study Results, Chart

This study’s “real-world” design permitted treatment with an adjustment of concomitant PD treatments.3


The lack of a blinded control group reduced the certainty that study findings were due to GOCOVRI®. No formal comparisons can be made between GOCOVRI® and other treatment regimens.3

Reductions were maintained over the 2 years of the open-label extension3

DBS, deep brain stimulation; MDS-UPDRS, Movement Disorders Society-Unified Parkinson's Disease Rating Scale.

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INDICATION and important safety information

GOCOVRI® (amantadine) extended release capsules is indicated:

  • For the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications
  • As adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes

It is not known if GOCOVRI is safe and effective in children.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
GOCOVRI is contraindicated in patients with creatinine clearance below 15 mL/min/1.73 m2.

WARNINGS AND PRECAUTIONS

Falling Asleep During Activities of Daily Living and Somnolence: Patients treated with Parkinson’s disease medications have reported falling asleep during activities of daily living. If a patient develops daytime sleepiness during activities that require full attention (e.g., driving a motor vehicle, conversations, eating), GOCOVRI should ordinarily be discontinued or the patient should be advised to avoid potentially dangerous activities.

Suicidality and Depression: Monitor patients for depression, including suicidal ideation or behavior. Prescribers should consider whether the benefits outweigh the risks of treatment with GOCOVRI in patients with a history of suicidality or depression.

Hallucinations/Psychotic Behavior: Patients with a major psychotic disorder should ordinarily not be treated with GOCOVRI because of the risk of exacerbating psychosis. Observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases.

Dizziness and Orthostatic Hypotension: Monitor patients for dizziness and orthostatic hypotension, especially after starting GOCOVRI or increasing the dose.

Withdrawal-Emergent Hyperpyrexia and Confusion: Rapid dose reduction or abrupt discontinuation of GOCOVRI, may cause an increase in the symptoms of Parkinson’s disease or cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, or slurred speech. Avoid sudden discontinuation of GOCOVRI.

Impulse Control/Compulsive Behaviors: Patients may experience urges (e.g. gambling, sexual, money spending, binge eating) and the inability to control them. It is important for prescribers to ask patients or their caregivers about the development of new or increased urges. Consider dose reduction or stopping medications.

ADVERSE REACTIONS
The most common adverse reactions (>10%) were hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension.

View the full Prescribing Information.

References:
  1. Pahwa R, Tanner CM, Hauser RA, et al. ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson disease (EASE LID Study). Jama Neurol. 2017;74(8):941-949.
  2. Oertel W, Eggert K, Pahwa R, et al. Randomized, placebo-controlled trial of ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson’s disease (Ease LID 3). Mov Disord. 2017;32(12):1701-1709.
  3. Tanner CM, Pahwa R, Hauser RA, et al. EASE LID 2: a 2-year open-label trial of Gocovri (amantadine) extended release for dyskinesia in Parkinson’s disease. J Parkinsons Dis. 2020;10(2):543–558.
  4. Elmer LW, Juncos JL, Singer C, et al. Pooled analyses of phase III studies of ADS-5102 (amantadine) extended-release capsules for dyskinesia in Parkinson’s disease. CNS Drugs. 2018;32(4):387-398.
  5. Data on file. Adamas Pharma LLC, Emeryville, CA.
  6. GOCOVRI® (amantadine) [Prescribing Information]. Emeryville, CA. Adamas Pharma LLC; 2021.
  7. Hauser RA, Kremens DE, Elmer LW, et al. Prevalence of dyskinesia and OFF by 30-minute intervals through the day and assessment of daily episodes of dyskinesia and OFF: novel analyses of diary data from Gocovri pivotal trials. J Parkinsons Dis. 2019;9(3):591-600.

GOCOVRI, the GOCOVRI logo, GOCOVRI Onboard, and the GOCOVRI Onboard logo, are trademarks of Adamas Pharmaceuticals, LLC or its related companies.
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