Gocovri (amantadine ER) / Supernus Pharma - LARVOL DELTA

Comparison of Three Oral Amantadine Formulations: A Population Pharmacokinetic Study (AAN 2024) - "Objective:Compare exposure parameters of three amantadine (AMT) formulations using an integrated population pharmacokinetic (PK) model.Background:Currently, three distinct AMT products are available in the US to treat manifestations of Parkinson's disease [PD]: the original immediate-release (IR) formulation (AMT-IR, [Symmetrel] administered 2-3 times daily), and two extended-release (ER) formulations; one with an IR component (AMT-IR/ER [Osmolex ER], administered once/day morning) and one with delayed-release technology (AMT-DR/ER [Gocovri], administered once/day bedtime)). Model-generated PK data confirm lack of product interchangeability reported in US product prescribing information. The higher plasma AMT concentrations in the morning and first half of the day with AMT-DR/ER are consistent with its indication for levodopa-related OFF episodes and dyskinesia as people with PD often wake up in an OFF state, and dyskinesia typically emerges following morning..."

Clinical • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease

Gocovri: Newly added patent in Orange Book (Orange Book) - Expiry on Dec 4, 2034

Patent • CNS Disorders • Parkinson's Disease

Recognition and Paradigm Shift in Treatment Strategies for OFF Fluctuations and Dyskinesia in Parkinson’s Disease (NeurologyLive) - "The neurology doctors discuss motor fluctuations and dyskinesia associated with Parkinson’s Disease."

Audio

Supernus Announces Second Quarter 2023 Financial Results (Supernus Pharmaceuticals Press Release) - "GOCOVRI® net product sales growth of 17% and 16% in the second quarter and first six months of 2023, respectively, compared to the same periods in 2022...SPN-830 (apomorphine infusion device) - Continuous treatment of motor fluctuations ('off' episodes) in Parkinson's disease (PD); The Company continues to expect to resubmit the New Drug Application for SPN-830 in the fourth quarter of 2023."

NDA • Sales • CNS Disorders • Parkinson's Disease

Extended-Release Amantadine Offers More Predictable Good ON Time for Those With Parkinson Disease (NeurologyLive) - "'Such observations may have important implications on the ability to participate in daily activities for [people with PD], and as such, the relationship between predictability and good quality of life merits further investigation,' first author Robert A. Hauser, MD, MBA...'When calculated in hours instead of percentages, participants had just over 5 hours per day of 'predictable' good ON time at baseline. This nearly doubled to just over 10 hours per day at Week 12 for those receiving amantadine extended-release vs just over 7 hours per day for placebo,' Hauser et al wrote."

Media quote

A population pharmacokinetic comparison of three amantadine formulations (IAPRD 2023) - P=NA | N=140 | "The population PK model predicted AMT plasma concentrations for the amantadine formulations. Comparative plasma-concentration time-profiles generated from the model confirm lack of product interchangeability reported in drug labeling, consistent with their different maintenance dosage and release technology. In contrast to AMT-IR and AMT-IR/ER, clinically used doses of AMT-DR/ER produced higher plasma concentrations in the morning and first half of the day, consistent with its intended use for levodopa-induced dyskinesia, which typically manifests with levodopa dosing in the morning and throughout the day."

Clinical data

Predictability of GOOD ON time during the waking day with amantadine extended-release capsules: a post-hoc analysis of pooled pivotal trials (IAPRD 2023) - "This post-hoc analysis of patient diary data suggests that in addition to reducing dyskinesia and OFF episodes, AMT-DR/ER may increase the predictability of GOOD ON time during the waking day."

Supernus Announces First Quarter 2023 Financial Results (GlobeNewswire) - "In April 2023, the Company had a constructive meeting with the U.S. Food and Drug Administration (FDA) to discuss the Complete Response Letter received in October 2022. Based on this meeting, the Company expects to resubmit the New Drug Application for SPN-830 in the fourth quarter of 2023....Net product sales were $140.6 million, compared to net product sales of $147.5 million for the same period in 2022. The decrease in net product sales was primarily due to a decrease in net product sales of Trokendi XR, partially offset by an increase in net product sales of both Qelbree and GOCOVRI. Excluding net product sales of Trokendi XR, first quarter 2023 total net product sales increased 25% compared to the same quarter last year."

FDA event • NDA • Sales • CNS Disorders • Parkinson's Disease

Management of Dyskinesia and Advances in Treatment of Parkinson’s Disease : Episode 9: Amantadine Formulations in Treatment of Dyskinesia in Parkinson Disease (NeurologyLive) - "Drs William G. Ondo and Rajesh Pahwa analyze the pharmacokinetics of different formulations of amantadine for treatment of dyskinesia in Parkinson disease....Daniel E. Kremens, MD, JD: We've mentioned that there are a couple of different formulations of amantadine. There's amantadine-IR [immediate release], amantadine-IR/ER [extended release], and amantadine-DR [delayed release]/ER."

Video

Management of Dyskinesia and Advances in Treatment of Parkinson’s Disease : Episode 10: Studies With Amantadine-DR/ER for Treatment of Dyskinesia (NeurologyLive) - "The expert neurology panel discusses clinical trial data of amantadine-DR/ER in treatment of dyskinesia and OFF episodes in Parkinson disease."

Video

Supernus Announces Fourth Quarter and Full Year 2022 Financial Results (Supernus Pharmaceuticals Press Release) - "Fourth quarter 2022 GOCOVRI® net product sales of $29.2 million increased 13% compared to fourth quarter of 2021; Full year 2022 GOCOVRI net product sales of $104.4 million increased 19% compared to full year 2021...SPN-830...The Company will be meeting with the U.S. Food and Drug Administration (FDA) in April 2023 to discuss the Complete Response Letter received in October 2022. We will announce the timing for our resubmission after our discussion with the FDA."

FDA event • Sales • CNS Disorders • Parkinson's Disease

Effect of GOCOVRI (Amantadine, Extended Release Capsules) on Gait in Parkinson's Disease (clinicaltrials.gov) - P4 | N=8 | Completed | Sponsor: Oregon Health and Science University | Recruiting ➔ Completed | N=12 ➔ 8

Enrollment change • Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

Synergistic effect of serotonin 1A and serotonin 1B/D receptor agonists in the treatment of L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rats (Neuroscience 2022) - "Extended-release amantadine (Gocovri™) is the only approved therapy for dyskinesia in Parkinson’s patients on the American market but is associated with neurological adverse effects and limited efficacy. Head-to-head comparison with amantadine showed superior performance of buspirone and zolmitriptan in this rat model. The robust anti-dyskinetic effect resulting from combined 5-HT1A and 5-HT1B/D agonism qualifies buspirone and zolmitriptan as a promising treatment for LID in Parkinson’s disease."

Preclinical • CNS Disorders • Parkinson's Disease

Supernus Announces Third Quarter 2022 Financial Results (GlobeNewswire) - “Third quarter 2022 GOCOVRI® net product sales of $27.9 million increased 16% compared to net product sales reported by Adamas Pharmaceuticals, Inc. (Adamas) in third quarter of 2021; First nine months 2022 GOCOVRI net product sales of $75.2 million increased 22% compared to net product sales reported by Adamas in the first nine months of 2021….For the three months ended September 30, 2022, net product sales were $172.7 million, a 19% increase over net product sales of $145.5 million for the same period in 2021. For the nine months ended September 30, 2022, net product sales were $485.6 million, an 18% increase over net product sales of $412.5 million for the same period in 2021. The increases in both periods were primarily due to net product sales of GOCOVRI...”

Commercial • Sales • CNS Disorders • Multiple Sclerosis • Parkinson's Disease

Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson’s disease. (PubMed, NPJ Parkinsons Dis) - P3 | "Recently, an amantadine delayed release/extended release (DR/ER) formulation (Gocovri) indicated for dyskinesia received additional FDA approval as an adjunct to levodopa for the treatment of OFF episodes. At Week 12, mean placebo-subtracted treatment difference in OFF time was -1.00 [-1.57, -0.44] h in the mITT population (n = 196), -1.2 [-2.08, -0.32] h in the ≥2.5 h subgroup (n = 102) and -0.77 [-1.49, -0.06] in the <2.5 h subgroup (n = 94). Amantadine-DR/ER-treated participants showed reduced MDS-UPDRS Part IV motor fluctuation subscores by week 2 that were maintained below baseline to Week 100."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Zydus receives tentative approval from the USFDA for Amantadine Extended-Release Capsules (Equitybulls) - "Zydus Lifesciences Limited's...U.S. subsidiary Zydus Pharmaceuticals (USA) Inc. has received tentative approval from the United States Food and Drug Administration (USFDA) to market Amantadine Extended-Release Capsules USP 68.5 mg and 137 mg (USRLD: Gocovri®)."

ANDA • CNS Disorders • Parkinson's Disease

"Do you know what to look for in amantadine induced livedo reticularis? Sold under Gocovri, Osmolex ER and Symmetrel. Be aware as you can stop the Parkinson’s medication and resolve the issue." (@MichaelOkun)

CNS Disorders • Movement Disorders • Parkinson's Disease

Synergistic effect of serotonin 1A and serotonin 1B/D receptor agonists in the treatment of L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rats. (PubMed, Exp Neurol) - "The strong anti-dyskinetic effect found with combined 5-HT1A and 5-HT1B/D agonism renders buspirone and zolmitriptan together a meaningful treatment for LID in PD."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Supernus Announces Second Quarter 2022 Financial Results (GlobeNewswire) - "GOCOVRI® prescriptions in second quarter 2022 reached 10,929, a 16% growth compared to second quarter 2021...For the three months ended June 30, 2022 operating earnings (GAAP) were $11.3 million, as compared to $34.1 million for the same period in 2021. For the six months ended June 30, 2022 operating earnings (GAAP) were $13.3 million, as compared to $47.3 million for the same period in 2021. The decreases in both periods were primarily due to activities to support...costs associated with GOCOVRI and amortization of acquired intangible assets from the Adamas Acquisition."

Commercial • CNS Disorders • Parkinson's Disease

Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy (clinicaltrials.gov) - P4 | N=11 | Terminated | Sponsor: Columbia University | Trial completion date: Sep 2023 ➔ Feb 2022 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2022 ➔ Feb 2022; PI left institution.

Trial completion date • Trial primary completion date • Trial termination • Cerebral Palsy • CNS Disorders

Supernus Announces First Quarter 2022 Financial Results (GlobeNewswire) - "GOCOVRI® prescriptions in first quarter 2022 reached 10,736, a 23% growth compared to first quarter 2021...Supernus Pharmaceuticals, Inc...today announced preliminary financial results for the first quarter of 2022, and associated Company developments....For the first quarter 2022, net product sales were $147.5 million, a 15% increase over $128.4 million for the same period in 2021. The increase was primarily due to net product sales of GOCOVRI..."

Commercial • CNS Disorders • Parkinson's Disease

Potential Utility of Amantadine DR/ER for Persons with Parkinson's Disease Under Consideration for Device-Aided Therapy (AAN 2022) - "Findings suggest AMT DR/ER should be considered as an option for PwP eligible for DAT."

CNS Disorders • Movement Disorders • Parkinson's Disease • Xerostomia

Experts Offer Advice on Newer Parkinson's Medications Cautions, Recommendations, and the Big Picture (Neurology Today) - '"Some of them are no big deal, but some are true game changers,' said Rajesh Pahwa, MD, FAAN...He pointed to extended-release amantadine (Gocovri) as the first drug shown to not only reduce off time but to also reduce dyskinesia. 'That to me is a huge benefit,' Dr. Pahwa said. 'All the other medications we use to treat off time make the dyskinesias worse.'"

Media quote

Immediate-release/extended-release amantadine (OS320) to treat Parkinson's disease with levodopa-induced dyskinesia: Analysis of the randomized, controlled ALLAY-LID studies. (PubMed, Parkinsonism Relat Disord) - "IR/ER-amantadine significantly reduced LID in ALLAY-LID II but not in ALLAY-LID I; post-hoc pooled data also indicated a positive treatment effect on LID."

Journal • CNS Disorders • Fatigue • Movement Disorders • Parkinson's Disease

Supernus Announces Preliminary Fourth Quarter and Full Year 2021 Financial Results (GlobeNewswire) - "Supernus Pharmaceuticals, Inc...today announced preliminary financial results for the fourth quarter and full year of 2021, and associated Company developments....Preliminary fourth quarter 2021 net product sales were $155.0 million, a 10% increase over $140.7 million in the same period in 2020. The increase was primarily due to net product sales of GOCOVRI....The Company will work closely with the FDA as it reviews the SPN-830 NDA. The Company is preparing for the commercial launch of SPN-830 in the first quarter of 2023, assuming timely approval by the FDA."

Launch US • Sales • CNS Disorders • Parkinson's Disease