No New Safety Signals With Long-Term 3,4-DAPP for Lambert–Eaton Myasthenic Syndrome

Among patients with Lambert-Eaton myasthenic syndrome (LEMS) in Europe, no new safety signals were reported after long-term management, according to study findings published in Neurology and Therapy.

Potassium channel blocker 3,4-diaminopyridine (3,4-DAP), a LEMS treatment which improves neurotransmission among patients, regularly fails to meet Good Manufacturing Practice standards of active ingredient consistency.

Gathering and collating observational safety data for 3,4-DAP and investigating long-term outcomes for patients with LEMS was a goal of the European LEMS registry. Researchers sought to present the analysis of registry results with respect to 3,4-DAP efficacy and safety among patients with LEMS.

Participation in the noninterventional European LEMS registry included 30 centers in Germany, Spain, Italy, and the UK, and 96 patients with a clinical assessment and abnormal neurophysiological testing or positive for voltage-gated calcium channels antibodies between May 2010 and August 2016. These participants also qualified for participation, of whom, there were 50 patients (52.1%) 3,4-DAPP (3,4-diaminopyridine phosphate), 21 (21.9%) 3,4-DAP, and 25 (26%) with other treatments (pyridostigmine, corticosteroids, immunoglobulins, and azathioprine). In total, 74 patients (77.1%) were exposed to 3,4-DAP.

Participation duration ranged from about half a year to almost 9 years, and in the follow-up period, 15 patients died and an additional 21 patients discontinued prematurely.

Myasthenia gravis quantitative scores were all similar. More than 50% of patients had a negative Romberg’s test plus a positive ataxia test. While muscle strength was maintained through follow-up, most patients experienced lessened reflex tone and limited functioning, though sustained or improvement in functioning was noted with the 3,4-DAPP treatment group. Inconsistent and sporadic functional improvement and regression was noted in the 3,4-DAP and other treatment groups. There were 55 adverse events (AEs) related to treatment reported by 32 patients, 8 of whom reported 9 serious AEs.

Researchers noted the study was limited by its noninterventional, observational design, the large number of patients lost, and a nonstandard approach to LEMS testing resulting in small sample sizes, and some LEMS patients may have been referred for other therapy and not enrolled in the registry.

Researchers concluded that, “No new safety signals were observed following long-term management of LEMS with 3,4-DAPP.” Poor health status and impaired quality of life are reported by an overwhelming majority of LEMS patients.

Disclosure: This research was supported by Biomarin International Ltd and SERB SA. Please see the original reference for a full list of disclosures. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Meisel A, Sieb JP, Le Masson G, Postila V, Sacconi S. The European Lambert-Eaton Myasthenic Syndrome Registry: Long-term outcomes following symptomatic treatment. Neurol Ther. Published online May 5, 2022. doi:10.1007/s40120-022-00354-8