Rytary (levodopa/carbidopa extended-release capsule) / Amneal - LARVOL DELTA

FDA mandates label updates to common Parkinson's meds based on seizure risk finding (Fierce Pharma) - "Healthcare providers should evaluate patients’ baseline vitamin B6 levels prior to and during treatment and supplement patients with the vitamin as necessary, the warning says....The label update affects Amneal’s Crexont and Rytary; Avion Pharmaceuticals’ Dhivy; Merck’s Sinemet and controlled-release Sinemet CR; Novartis’ Stalevo; and AbbVie’s Duopa. Also affected is AbbVie’s newer Vyalev, a subcutaneous treatment that delivers prodrugs of carbidopa and levodopa via an infusion pump system....In its safety review, the FDA identified 14 causes of seizures linked to vitamin B6 deficiency in patients taking the common Parkinson’s disease drugs, including 13 instances that were submitted to the FDA’s adverse events reporting system and 1 reported in medical literature."

Adverse events • FDA event • Parkinson's Disease

COMPUTATIONAL MODELING TO OPTIMIZE CONTROLLED RELEASE FORMULATIONS OF LEVODOPA FOR PARKINSON'S DISEASE (ADPD 2026) - "To minimize the influence of gastric emptying, the model supports multiparticulate pellets with coatings that enable differential release along the small intestine, similar to the mechanism employed in Rytary. The proposed CRF strategy is expected to reduce motor complications by maintaining stable plasma levodopa levels and to improve patient compliance through fewer daily doses. Beyond levodopa, this modeling framework illustrates how computational tools can accelerate the rational design of controlled drug delivery systems."

CNS Disorders • Movement Disorders • Parkinson's Disease

Protein-induced Motor Fluctuations Despite Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion: A Case Report (AAN 2026) - " A 41-year-old right-handed male with young-onset Parkinson's disease diagnosed at age 35 was switched over to fCD/fLD pump due to increasing wearing off fluctuations after failing best medical treatment with immediate-release carbidopa/levodopa (IR CD/LD) and extended-release carbidopa/levodopa (Rytary and Crexont). Even though fCD/fLD pump is a subcutaneous levodopa infusion, it seems that oral protein interferes with its central effect. We propose that amino acids, the products of protein breakdown, may compete with levodopa for transport into the central nervous system at the L-type amino-acid transporter 1 (LAT1) protein located in the blood-brain barrier."

Case report • Clinical • CNS Disorders • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease

Switching to CREXONT® Improves "Good On" Time and Reduces Motor Fluctuations in Parkinson's Disease: Interim Results from the Real-world ELEVATE-PD Phase Four Study (AAN 2026) - "Objective: Evaluate interim outcomes from the real-world study of CREXONT, assessing its impact to extend "Good On" time and reduce "Off" time in PD patients after switching from other levodopa-based therapies.Background: CREXONT, a novel extended-release carbidopa-levodopa formulation containing a mucoadhesive polymer, is designed to improve levodopa delivery and absorption, enhancing therapeutic benefit. CREXONT substantially increased "Good On" time, reduced "Off" time, and improved motor function in PD patients across all therapy groups, confirming that switching patients from other levodopa-based therapies to CREXONT offers meaningful improvements in symptom control through the day."

Clinical • Real-world • Real-world evidence • CNS Disorders • Infectious Disease • Movement Disorders • Nephrology • Parkinson's Disease • COMT

Treatment strategies for motor fluctuations in Parkinson's disease: a systematic review of efficacy, functionality, and drug accessibility with a focus on Latin America. (PubMed, Front Pharmacol) - "High-certainty evidence supports the efficacy of extended-release levodopa (IPX066), opicapone, pramipexole, rotigotine, and safinamide in reducing OFF-time, although improvements in functional disability and quality of life were modest or inconsistent. Moderate-certainty evidence supports device-aided therapies, including levodopa-carbidopa intestinal gel (LCIG), subcutaneous foslevodopa-foscarbidopa, and continuous apomorphine infusion, which achieved larger effects on OFF-time and functional outcomes...In contrast, several newer therapies-such as IPX066, opicapone, istradefylline, and foslevodopa-foscarbidopa-were unavailable in most Latin American markets, and price differentials for controlled-release or add-on therapies were often several-fold higher after PPP adjustment...The Latin American region exemplifies these disparities, with limited regulatory availability, heterogeneous pricing, and insufficient inclusion of novel agents in national formularies...."

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

Symptom improvement in a South Asian patient with Parkinson's disease treated with immediate- and extended-release carbidopa-levodopa: a case report. (PubMed, J Med Case Rep) - "Immediate-release carbidopa-levodopa given three to four times daily remains the most common medication regimen for managing Parkinson's disease symptoms of tremor and rigidity, with benefits noted in responsive patients for 2 to 3 hours. Extended release and combination formulations of carbidopa-levodopa that combine short- and long-acting medications in one capsule provide symptom relief for responsive patients for 4-6 hours and should be considered when the benefit from immediate-release carbidopa-levodopa is limited. Little has previously been published about the potential for variations in carbidopa-levodopa formulation responsiveness in South Asians, though it has been suggested that Western guidelines for managing "off" periods where carbidopa-levodopa is less effective, may not apply to other ethnicities (Bhidayasiri et al. in Expert Rev Neurother 15(11):1285-1297, 2015). As exemplified in this case, greater understanding of non-Caucasian..."

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

Plant-Based Therapies To Ameliorate Neuroinflammation In Parkinson's Disease, Alzheimer's Disease And Epilepsy: A Narrative Review. (PubMed, Chem Biodivers) - "Some of the examples are curcumin, resveratrol, ginsenosides, cannabidiol, notoginseng, quercetin etc. Clinical studies also indicate that certain plant-based formulations like Wei Li Bai, IPX066, Bushen huoxue etc., can be effective alternatives to presently available remedies. The review is an attempt at assimilating the information from available literature on the role of different neurotransmitters involved in neuroinflammation and their connection in AD, PD, and, Epilepsy and applications of plant-based therapies in the prevention and cure of the above-mentioned diseases."

Journal • Alzheimer's Disease • CNS Disorders • Epilepsy • Inflammation • Movement Disorders • Parkinson's Disease

Extended-Release Carbidopa-Levodopa: How is IPX203 different from IPX066? (ANA 2024) - "These data confirm that both IPX066 and IPX203 have ER LD pharmacokinetic profiles. Levodopa concentrations were sustained for a longer duration with IPX203 compared to IPX066; the pharmacodynamic effects were consistent with LD pharmacokinetics."

CNS Disorders • Parkinson's Disease

Extended-release carbidopa-levodopa: How is IPX203 different from IPX066? (ATMRD 2024) - No abstract available.

Novel Non-opioid Post-surgical Pain Treatment in Females (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Northwestern University | N=60 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Pain

IPX203 vs Immediate-Release Carbidopa-Levodopa for the Treatment of Motor Fluctuations in Parkinson Disease: The RISE-PD Randomized Clinical Trial. (PubMed, JAMA Neurol) - P3 | "A total of 770 patients were screened, 140 were excluded (those taking controlled-release carbidopa-levodopa apart from a single daily bedtime dose, Rytary (Amneal Pharmaceuticals), additional carbidopa or benserazide, or catechol O-methyl transferase inhibitors or who had a history of psychosis within the past 10 years), and 630 were enrolled in the trial. In this study, IPX203 provided more hours of good on-time per day than immediate-release carbidopa-levodopa, even as IPX203 was dosed less frequently. ClinicalTrials.gov Identifier: NCT03670953."

Clinical • Journal • CNS Disorders • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Novel Non-opioid Post-surgical Pain Treatment in Females (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Northwestern University | Trial completion date: Jan 2023 ➔ Jan 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Pain

Parkinson’s Disease Patient Characteristics in a US Real-World Study of Opicapone (ANA 2022) - "Background : Opicapone is an oral, selective, once-daily catechol-O-methyltransferase (COMT) inhibitor used as adjunctive treatment to carbidopa/levodopa (CD/LD) in patients with PD experiencing “OFF”-episodes...11.1% of patients used entacapone before enrollment and were switched to opicapone... Opicapone was added to a variety of CD/LD formulations, including over 20% of patients utilizing Rytary. While the study was conducted during the ongoing pandemic and investigators could initiate treatment via telemedicine, most investigators elected to initiate patients on opicapone with an in-person visit. Findings from OPTI-ON will further characterize the PD population treated with opicapone and real-world clinician- and patient-reported outcomes data in the US will complement results from previous controlled clinical trials."

Clinical • Real-world evidence • CNS Disorders • Parkinson's Disease

Learning and predicting Levodopa regimens from wearable sensors: A novel machine learning approach (MDS Congress 2022) - " Our wearable-based RL policies suggest that the original n=26 study patients would experience lower bradykinesia (and unchanged dyskinesia) if switched to controlled-release L-dopa formulations such as Rytary... We show that pairing machine learning with even small quantities of wearable movement tracker data can offer novel, generalizable clinical insights and medication strategies, which can be used to improve care for other PD patients for whom wearable data are not available."

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

"PPMI Parkisons progression marker initiative sponsored by the MJF foundation. Also finished a trial for a rytary type med. Stage 1, what trial is yours?" (@rjmcane2006)

Difference in rural and urban Medicare prescription pattern for Parkinson's disease in Hawai'i. (PubMed, Clin Park Relat Disord) - "In rural Hawai'i, Rytary, Rotigoitne and selegiline were rarely prescribed. In the state of Hawai'i, there is an urban-rural access gap to neurologists as evidenced by Medicare prescription pattern. Further study is needed to understand the reasons for rural-urban differences in prescription patterns and their impact on outcomes."

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

AMNEAL PHARMACEUTICALS, INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) (Market Screener) - "Specialty segment net revenue decreased $10.8 million during the thee months ended March 31, 2022 as compared to the prior year period, driven by the loss of exclusivity of Zomig® nasal spray as well as a decline in our other non-promoted products. Net revenue for our promoted products, including Rytary® and Unithroid®, declined 6% and increased 13%, respectively, due to the timing of shipments as prescription growth remained strong for both products...Research and Development Specialty R&D expenses for the three months ended March 31, 2022 were $9.6 million, as compared to $12.1 million for the three months ended March 31, 2021. The $2.5 million decrease from the prior year period was primarily attributable to a decrease in in-licensing and upfront milestone payments of $5.0 million and a reduction in IPX-203 spend as the project neared completion, partially offset by increased spend of $3.0 million associated with the KSP Acquisition."

Commercial • CNS Disorders • Migraine • Pain • Parkinson's Disease

BRIEF—Bora Pharma links with Bright Future on PD drug (The Pharma Letter) - "Taiwan drug maker Bora Pharmaceuticals has signed a distribution deal with its Hong Kong-based counterpart Bright Future to supply the extended release (ER) combo drug Numient (carbidopa/levodopa) to treat Parkinson's disease in China, including Hong Kong and Macau....Bora is Amneal's contracted manufacturer for Numient, and holds the commercial rights to the drug in many other Asian countries including Japan, South Korea and Thailand."

Licensing / partnership • CNS Disorders • Parkinson's Disease

Novel Non-opioid Post-surgical Pain Treatment in Females (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Northwestern University; Not yet recruiting ➔ Recruiting

Enrollment open • Pain

AMNEAL PHARMACEUTICALS, INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) (Market Screener) - "Specialty net revenue for the three months ended September 30, 2021 was $93 million, an increase of $5 million, or 6%, compared to the three months ended September 30, 2020. The overall growth was primarily attributed an increase in Rytary® and Unithroid® revenue of $4 million, or 11%, and $2 million, or 18%, respectively, compared to the prior year period, partially offset by a decline in non-promoted Specialty brands."

Sales • CNS Disorders • Parkinson's Disease

Novel Non-opioid Post-surgical Pain Treatment in Females (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: Northwestern University

New P2 trial • Pain

Drugs for Parkinson's disease. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Real-World Experience with Carbidopa-Levodopa Extended-Release Capsules (Rytary): Results of a Nationwide Dose Conversion Survey. (PubMed, Parkinsons Dis) - "Moreover, rapid patient follow-up after initial dose conversion to allow for further dose adjustments plays a critical role in achieving success. Gaining experience over time is important for satisfactory conversion."

Clinical • Journal • Real-World Evidence

Comparison chart: Drugs for Parkinson's disease. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Opicapone (Ongentys) - a COMT inhibitor for Parkinson's disease. (PubMed, Med Lett Drugs Ther) - No abstract available

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