Firdapse led to clinically significant improvements, compared with a placebo, in adult patients with Lambert-Eaton myasthenic syndrome (LEMS), according to full results of a Phase 3 trial.
The results were published in the Journal of Clinical Neuromuscular Disease in a study titled “Amifampridine Phosphate (Firdapse) Is Effective in a Confirmatory Phase 3 Clinical Trial in LEMS.”
Firdapse (amifampridine phosphate), developed by Catalyst Pharmaceuticals, was approved by the U.S. Food and Drug Administration (FDA) in December for adults with LEMS, making it the first approved therapy in the U.S. for the condition.
“The results of this second pivotal Phase 3 trial again demonstrate that Firdapse is effective for the treatment of LEMS,” Gary Ingenito, MD, PhD, chief medical officer of Catalyst Pharmaceuticals said in a press release. “We are pleased to offer access, for all adult LEMS patients, to the first FDA approved, evidence-based treatment available in the United States.”
Firdapse, taken as oral tablets, is a neuronal potassium channel blocker, which allows for an influx of calcium. It also induces the secretion of synaptic vesicles to release more of the neurotransmitter acetylcholine (ACh) — a shortage of ACh is the underlying cause of LEMS — into the synaptic space, thereby enhancing neuromuscular transmission and improving muscle function. Synapses are the junctions between two nerve cells that allow them to communicate.
The FDA’s approval was based on two Phase 3 trials, LMS-002 and LMS-003, which showed the therapy’s effectiveness, but only now have the full results of LMS-003 been published.
The LMS-003 (NCT02970162) was a multicenter, double-blind, placebo-controlled study to evaluate the effectiveness and safety of multiple doses of Firdapse compared with a placebo in LEMS patients.
A total of 26 adults with LEMS, with a mean age of 54.2 years, were randomly assigned to a four-day oral treatment with either 10 mg of Firdapse (13 patients) or a placebo (13 patients) taken three to four times per day for a daily total dose of 30 mg to 80 mg.
All the participants had previously been given a stable dose of Firdapse for at least a week. At the end of the study, eligible patients were allowed to return to open-label treatment with Firdapse.
The main objective was to assess the tolerability and clinical efficacy of Firdapse over the placebo using the quantitative myasthenia gravis (QMG) score — a 13-item physician-rated assessment of arm and leg strength, face and neck muscle performance, swallowing, speech, grip strength, forced respiration, and gaze — and the subjects’ global impression (SGI), a seven-point scale in which patients rate their global impression of the therapy on LEMS symptoms.
Exploratory efficacy parameters included the Triple Timed Up and Go walk test (3TUG), which is a functional mobility test, and the QMG-limb domain score — the total sum of arm and leg raising maneuvers used to assess muscle weakness.
Additional objectives used Clinical Global Impression–Improvement (CGI-I) scores.
The results showed that treatment with Firdapse led to clinically significant improvements compared with a placebo in both QMG and SGI scores.
Firdapse’s efficacy was further supported with improvements seen in the 3TUG and the QMG-limb domain tests. A significant proportion of placebo patients (61.5%) took longer to perform the 3TUG test compared with those treated with Firdapse (7.7%).
The scores of the CGI-I test at day four were lower (which means the condition improved) with Firdapse (3.8) compared with the placebo (5.5).
“On further analysis of other 9 QMG items, the forced vital capacity and head lift to 45 degrees showed a statistically significant difference in favor of amifampridinephosphate,”the researchers wrote.
In the Firdapse-treated group, three patients reported side effects, which included back pain, pain in their extremities, and headaches. The most common side effect in the placebo group were muscle weakness and fatigue.