The possibility of obtaining marketing authorization of orphan pharmaceutical compounding preparations: 3,4-DAP for Lambert-Eaton Myasthenic Syndrome

Wilde, Sofieke de; Jong, Maria G H de; Lipka, Alexander F.; Guchelaar, Henk‐Jan; Schimmel, Kirsten J. M.

doi:10.1016/j.ejps.2017.11.025

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…3,[6][7][8][9][10][11][12] 3,4-DAP was the most effective symptomatic treatment available and considered to be first-line for both autoimmune and paraneoplastic LEMS. 1,7,13 3,4-DAP was obtained by patients through a compassionate use program, which allows patients access to unapproved medications for diseases where comparable alternatives are unavailable. Despite the long history of use of 3,4-DAP for LEMS, orphan drug designation from the United States Food and Drug Administration (FDA) was not obtained until 2009 because of issues relating to variability and reliability of the product between batches.…”

Section: Treatmentmentioning

confidence: 99%

Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug

et al. 2019

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Objective: The purpose of this article is to review the literature for both 3,4-diaminopyridine (3,4-DAP) and amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). Amifampridine (Firdapse) is the salt form of 3,4-DAP and was approved by the Food and Drug Administration for the treatment of LEMS. Data Sources: PubMed, TRIP database, and EMBASE searches were conducted without a back date (current to June 2019) utilizing the following search terms: amifampridine, 3,4-diaminopyridine, and Lambert-Eaton myasthenic syndrome. Completed trials were also reviewed at clinicaltrials.gov. Study Selection and Data Extraction: Criteria for article inclusion consisted of human subjects, age ≥18 years, phase II or III clinical trials, and English language for both drugs. Observational and pharmacokinetic studies for amifampridine were also included. Data Synthesis: Prior to the approval of amifampridine, 3,4-DAP was first-line for the management of LEMS symptoms. Two phase III trials have evaluated amifampridine to confirm efficacy, both showing superiority over placebo in the management of LEMS symptoms, with minimal adverse effects. A significant improvement in both quantitative myasthenia gravis scores and Subjective Global Impression scores was established at days 4 and 14. Relevance to Patient Care and Clinical Practice: With an improved stability profile and decreased dose variability, amifampridine will likely assume the role of first-line management of LEMS. Conclusions: Amifampridine has been shown to improve symptoms of LEMS and is generally well tolerated.

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Section: Treatmentmentioning

confidence: 99%

Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug

et al. 2019

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“…For over 30 years, 3,4-diaminopyridine had been administered to LEMS patients on an unlicensed basis through compounding pharmacies since it was first studied in LEMS patients in 1983. , Beginning in the early 1990s, at the request of the Muscular Dystrophy Association, Jacobus Pharmaceutical Company provided 3,4-diaminopyridine for free to an estimated 100–200 LEMS patients for approximately 20 years under compassionate use (also known as expanded access), which allows patient access to unapproved, investigational medications for diseases where comparable alternatives are unavailable. , At the time, Jacobus Pharmaceutical Company did not seek FDA approval given the substantial investment and small patient population. As well, variability and unreliability of drug product existed between different preparations 3,4-diamionpyridine free base…”

Section: Introductionmentioning

confidence: 99%

An Efficient Undergraduate Synthesis of the Exorbitantly Priced Lambert–Eaton Myasthenic Syndrome Drug Amifampridine

Garcia

Tran

et al. 2023

J. Chem. Educ.

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An efficient synthesis of the exorbitantly priced Lambert–Eaton myasthenic syndrome drug amifampridine was developed and applied in the second-semester undergraduate organic chemistry laboratory. The two-step synthesis entails a nucleophilic aromatic substitution reaction of commercial 4-chloro-3-nitropyridine with methanolic ammonia to afford 4-amino-3-nitropyridine. Subsequent palladium-catalyzed nitro reduction provides amifampridine in high yield and purity. Amifampridine can alternatively be prepared by advanced undergraduate students in four linear steps beginning with 4-hydroxypyridine. Nitration of 4-hydroxypyridine to 4-hydroxy-3-nitropyridine and subsequent treatment with phosphoryl chloride provides the intermediate 4-chloro-3-nitropyridine, which is then subjected to the SNAr and reduction reactions to cleanly afford amifampridine without the need for column chromatography.

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Amifampridine for the treatment of Lambert-Eaton myasthenic syndrome

2019

Expert Review of Clinical Immunology

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The possibility of obtaining marketing authorization of orphan pharmaceutical compounding preparations: 3,4-DAP for Lambert-Eaton Myasthenic Syndrome

Cited by 3 publications

References 21 publications

Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug

Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug

An Efficient Undergraduate Synthesis of the Exorbitantly Priced Lambert–Eaton Myasthenic Syndrome Drug Amifampridine

Amifampridine for the treatment of Lambert-Eaton myasthenic syndrome

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