Osmolex ER (amantadine ER) / Supernus Pharma - LARVOL DELTA

Treatment for Dyskinesia in Parkinson's Disease: A Network Meta-analysis of Randomized Controlled Trials. (PubMed, Mov Disord) - "This RCT-based NMA identifies and ranks nine efficacious interventions for dyskinesia in PD. GPi-DBS may be the most effective therapy for treating dyskinesia, with IR amantadine ranking highest among oral medications. Novel anti-dyskinetic medications are associated with less-favorable tolerance profiles."

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

Recent advancements and updates in the management of Parkinson's disease (Neuroscience 2024) - "Dyskinesia was significantly decreased in the studies of immediate-release/extended-release amantadine (OS320) with treatment differences of ≥8. Conclusion Pharmacological therapies such as ND0612, Opicapone, Safinamide, and LCIG have the potential to improve the Quality of Life in PD by decreasing motor symptoms and dyskinesias. STN-DBS can also be a cutting-edge measure in the overall management of patients. Further studies should be directed toward the use of combination therapies and precision-based treatment regimens for refractory cases."

Late-breaking abstract • CNS Disorders • Parkinson's Disease

Zydus receives USFDA final approval for Amantadine ER capsules 68.5 mg (Indian Pharma Post) - "Zydus Lifesciences Limited has received final approval from the United States Food and Drug Administration (USFDA) to market Amantadine extended-release capsules, 68.5 mg, and tentative approval for 137 mg (USRLD: Gocovri (amantadine) extended-release capsules, 68.5 mg and 137 mg). Amantadine extended-release capsules are indicated for the treatment of dyskinesia in patients with Parkinson's disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications."

FDA approval • CNS Disorders • Parkinson's Disease

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

Minimizing Variations in Patient’s Experience with Levodopa Therapy in Parkinson's Disease : Episode 4: Amantadine Extended Release for the Management of Dyskinesia and OFF Episodes (NeurologyLive) - "Robert Hauser, MD, MBA, talks about amantadine extended release for management of dyskinesia and OFF episodes."

Video

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

Management of Dyskinesia and Advances in Treatment of Parkinson’s Disease : Episode 11: Amantadine DR/ER for Dyskinesia in Parkinson Disease: Safety Profile and Ideal Patient (NeurologyLive) - "The expert panel reviews the safety profile of amantadine DR/ER and who may be an ideal patient for its use in patients with Parkinson disease experiencing dyskinesia."

Video

Management of Dyskinesia and Advances in Treatment of Parkinson’s Disease : Episode 12: Use of Other Amantadine Formulations in Parkinson Disease (NeurologyLive) - "The expert neurology panel shares their clinical experience with different formulations of amantadine in management of dyskinesia in patients with Parkinson disease."

Video

Proteasome Regulatory Atpases PSMC2 and PSMC6 Modulate Proteosome Inhibitor Sensitivity and Correlate with Survival in Multiple Myeloma (ASH 2022) - "The proteasome inhibitor (PI) bortezomib (BTZ) is a potent, selective, and reversible drug that dramatically improved the prognosis of multiple myeloma (MM) patients and remains the backbone of induction therapy for transplant-eligible new diagnosis MM (NDMM), but response to therapy remains highly variable... We interrogated gene expression profiles (GEP) from the randomized, phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study that compared BTZ with high-dose dexamethasone (DEX) in RRMM patients who had received 1-3 prior therapies...Finally, we used shRNA to knockdown PSMC2 in RPMI8226 and ARH77 cells and tested their sensitivity to BTZ and carfilzomib (CFZ). Analysis of the APEX dataset revealed that increased expression of genes PSMC2 and PSMC6, members of the heterohexameric ATPase ring of the 19S RP, correlated with poorer OS (PSMC2- Figure 1A, PSMC6- Median OS 320 versus 620 days for upper and lower tertile PSMC6, respectively)......"

Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • Transplantation • PSMC2 • PSMC6 • SDC1

"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

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

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 Pharmaceuticals Completes Acquisition of Adamas Pharmaceuticals (GlobeNewswire) - "Supernus Pharmaceuticals...today announced that it has successfully completed its previously announced acquisition of Adamas Pharmaceuticals...'In addition, the acquisition adds a new growth catalyst, diversifies our revenue base and cash flow, and is expected to be significantly accretive in 2022'....Strengthens Parkinson’s disease portfolio with GOCOVRI® (amantadine) extended release capsules...and Osmolex ER® (amantadine) extended release tablets, approved for the treatment of Parkinson’s disease and drug-induced extrapyramidal reactions in adult patients. Potential synergies of $60 million to $80 million in year one due to strong overlap with existing infrastructure. The acquisition is expected to be significantly accretive in 2022."

M&A • CNS Disorders • Multiple Sclerosis • Parkinson's Disease

Osmotica Pharmaceuticals plc Reports Third Quarter 2021 Results and Provides Business Update (GlobeNewswire) - "Osmotica Pharmaceuticals plc...today announced business highlights and financial results for the three months ended September 30, 2021....Net product sales increased $1.6 million to $2.2 million for the three months ended September 30, 2021, compared to $0.6 million for the three months ended September 30, 2020. The increase was primarily attributable to an increase in sales of Upneeq, which was commercially launched in September 2020, partially offset by a decrease in product sales of Osmolex, reflecting the divestiture of the product in January 2021."

Commercial • CNS Disorders • Parkinson's Disease

Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy (clinicaltrials.gov) - P4; N=10; Recruiting; Sponsor: Columbia University; Trial completion date: Sep 2021 ➔ Sep 2023; Trial primary completion date: Sep 2021 ➔ Sep 2022

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

Supernus Pharmaceuticals to Acquire Adamas Pharmaceuticals Strengthening its CNS Product Portfolio (GlobeNewswire) - "Supernus Pharmaceuticals, Inc...and Adamas Pharmaceuticals, Inc...today announced a definitive agreement for Supernus to acquire Adamas through a tender offer for $8.10 per share in cash...payable at closing plus two non-tradable contingent value rights (CVR) collectively worth up to $1.00 per share in cash (or an aggregate of approximately $50 million), for a total consideration of $9.10 per share in cash....The first CVR, worth $0.50 per share, is payable upon achieving net sales of GOCOVRI® of $150 million in any four consecutive quarters between closing and the end of 2024. The second CVR, worth $0.50 per share, is payable upon achieving net sales of GOCOVRI of $225 million in any four consecutive quarters between closing and the end of 2025. The transaction is expected to close in late fourth quarter 2021 or in early first quarter 2022. The transaction will provide Supernus with two marketed products: GOCOVRI (amantadine)...and Osmolex ER®..."

M&A • CNS Disorders • Parkinson's Disease

Adamas Reports Second Quarter 2021 Financial Results (Businesswire) - "Total revenues were $22.0 million for the second quarter of 2021, consisting of GOCOVRI product sales of $20.1 million, OSMOLEX ER product sales of $0.5 million and royalty revenue earned on net sales of NAMZARIC® (memantine hydrochloride extended release and donepezil hydrochloride) capsules of $1.4 million. GOCOVRI product sales were up 12% compared to $18.0 million in the same period in 2020....SG&A expenses for the second quarter of 2021 were $29.2 million, compared to $23.2 million for the same period in the prior year. SG&A expenses in the second quarter of 2021 were primarily attributable to sales force costs and external spend dedicated to GOCOVRI commercialization and the related administrative support as well as the integration and initial promotion of OSMOLEX ER."

Commercial • Sales • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Osmolex ER: Newly added patents in Orange Book (Orange Book) - Expiry on November 23, 2025 and January 22, 2028

Patent • CNS Disorders • Parkinson's Disease

"$ADMS Adamas Completes Acquisition of OSMOLEX ER® https://t.co/idon1ERY4i" (@otcdynamics)

Adamas Completes Acquisition of OSMOLEX ER (GlobeNewswire) - "Adamas Pharmaceuticals...today announced the closing of the settlement of patent litigation with Osmotica Pharmaceutical US LLC, a subsidiary of Osmotica Pharmaceuticals plc and completes the acquisition of the global rights to OSMOLEX ER®...We look forward to leveraging the unique opportunities and benefits of each therapy in our portfolio, with the growth of GOCOVRI remaining our primary focus."

Licensing / partnership • Patent • CNS Disorders • Parkinson's Disease

Osmotica Pharmaceuticals plc Announces Agreement to Settle Patent Litigation with Adamas (GlobeNewswire) - "Osmotica Pharmaceuticals plc....announced today that its subsidiary Osmotica Pharmaceutical US LLC has entered into an agreement to settle its ongoing patent litigation with Adamas Pharmaceuticals, Inc. related to OSMOLEX ER. Under the terms of the agreement, both parties will drop their respective claims relating to the patent litigation, and Adamas will acquire the global rights to OSMOLEX ER for $7.5 million. The agreement is expected to close in early 2021."

Patent • CNS Disorders • Parkinson's Disease

Adamas Announces Agreement to Amend Royalty-Backed Loan Agreement with HealthCare Royalty Partners (GlobeNewswire) - "Adamas Pharmaceuticals, Inc....today announced it has entered into an agreement to amend certain key terms of its Royalty-Backed Loan agreement ('Royalty-Backed Loan') with HealthCare Royalty Partners ('HCR'). The key terms amended are summarized as follows: Revised to provide for repayment from a royalty on OSMOLEX ER® on the same terms as, and in addition to, the royalty for GOCOVRI®....The amendment will come into effect upon closing the acquisition of OSMOLEX ER in early 2021."

Commercial • Financing • CNS Disorders • Parkinson's Disease

Osmolex ER: Newly added patents in Orange Book (Orange Book) - Expiry on November 28, 2025, March 13, 2030, February 15, 2038

Patent • CNS Disorders • Parkinson's Disease

Effects of Renal Impairment on the Pharmacokinetics of Once-Daily Amantadine Extended-Release Tablets. (PubMed, CNS Drugs) - "Renal impairment was associated with reduced amantadine clearance. Based on pharmacokinetic modeling and simulations, dose regimens were recommended for subjects with impaired renal function to provide systemic amantadine exposure similar to subjects with normal renal function taking a once-daily extended-release amantadine tablet."

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

"Pero que alguien se lo explique a los 320 alcaldes que están haciendo lo que se les da la gana" (@JoseGonzaloQue1)