Sometimes, researchers find beneficial medications during clinical trials. Other times, the therapy just falls short. According to Myasthenia Gravis News, the latter is true for Firdapse (amifampridine phosphate). The therapy, which was being tested to treat patients with MuSK-antibody positive myasthenia gravis (MuSK-MG), failed to meet its endpoints in a Phase 3 clinical trial.
Myasthenia Gravis
If you’re looking to understand myasthenia gravis (MG), look no further than its name. The progressive autoimmune neuromuscular disorder, named for the Greek and Latin words for “grave muscle weakness,” causes muscle weakness and fatigue that worsens with activity. Altogether, myasthenia gravis affects voluntarily controlled muscle groups such as the eyes, the mouth, and the arms and legs. While there is no cure for MG, many patients live full lives; only 10% of patients will experience severe and life-threatening respiratory issues.
While MG can be inherited (congenital myasthenia gravis), most causes result from antibodies. Antibodies, which should protect the body from foreign invaders, instead attack proteins that contribute to nerve-muscle communication. Symptoms include:
- Double vision
- Eyelid drooping
- Changes in gait or posture
- Widespread muscle fatigue
- Changes in speech (slurring)
Learn more about myasthenia gravis here.
MuSK-MG
In an article in Neurologic Clinics, the authors explain that approximately 80% of patients with MG have acetylcholine receptor (ACHR) antibodies. But what about those who don’t? Patients without ACHR antibodies were once known as antibody negative (SNMG). However, researchers discovered that many of these patients (around 70%) had muscle specific tyrosine kinase (MuSK) antibodies. As a result, the body mistakenly attacks MuSK-producing cells. Additionally, researchers note that MuSK-MG antibodies:
are found in around 30–40% of ACHR negative MG patients and are associated with specific clinical phenotypes. One is a predominantly bulbar form with fewer ocular symptoms than in ACHR positive MG, [while] others show an isolated head drop or symptoms indistinguishable from ACHR positive MG.
Bulbar represents the bulbar region, or the brain stem. Those with a “predominantly bulbar form” of MuSK-MG are more likely to have difficulty chewing, speaking, and swallowing.
About Firdapse
Developed by Catalyst Pharmaceuticals, Firdapse is an orally-administered voltage-gated potassium channel blocker. Basically, it helps raise acetylcholine levels. As a result, Firdapse should have allowed for better nerve-muscle communication.
Yet despite positive Phase 2b trial data, Firdapse failed to improve Myasthenia Gravis Activities of Daily Living or Quantitative Myasthenia Gravis scores. During the Phase 3 trial, 70 patients with MuSK-MG received either a placebo (3-4x daily for 10 days) or 10mg Firdapse. Although it was fairly safe and well-tolerated, with nausea and diarrhea as side effects, it still did not improve patient outcomes. Moving forward, Catalyst Pharmaceuticals hopes to create a more targeted treatment for patients with MuSK-MG.
Beyond MuSK-MG, Firdapse is approved to treat Lambert-Eaton myasthenic syndrome (LEMS), and is also being explored as a potential treatment for spinal muscular atrophy (SMA).
