Clinical Background

Congenital myasthenic syndromes (CMS) are a rare group of genetic disorders characterized by fatigable weakness of skeletal muscles with onset at or shortly after birth or early childhood. CMS can involve defects or mutations in at least 20 different genes. It affects approximately 3 per 1 million persons. In rare cases, symptoms may not manifest until later in childhood. The severity and course of the disease are variable, ranging from minor symptoms to progressive disabling weakness. In some cases, CMS symptoms may be mild, but sudden, severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be caused by fever, infections, or excitement.1-3

The diagnosis of CMS is based on clinical findings, including a decremental EMG response of the compound muscle action potential (CMAP) on low-frequency stimulation, and the absence of anti-acetylcholine receptor and anti-MuSK antibodies in the serum, which are diagnostic for myasthenia gravis.1-3

Amifampridine Phosphate in CMS

Catalyst is continuing clinical development and with the goal of securing FDA approval for amifampridine phosphate, a neuronal potassium channel blocker, for the treatment of CMS.

CMS Trial (CMS-001)

CMS-001 is a phase 3, randomized, double-blind, controlled, outpatient 2 period, 2 treatment crossover study that is designed to evaluate the efficacy and safety of amifampridine phosphate in patients (aged 2 years and above) diagnosed with certain genetic subtypes of CMS.

Efficacy measures  


  • Change in SGI score* from baseline to:
    • End of week 5 (period 1)
    • End of week 8 (period 2)



  • Change in the composite MFM score from baseline to:
    • End of week 5 (period 1)
    • End of week 8 (period 2)

Safety assessments

Patient safety is monitored throughout the trial and EAP

Study Design

Click the image to enlarge

Following the experimental treatment period 1, a stable dose will be reestablished, followed by crossover treatment in period 2.

Catalyst is making amifampridine phosphate available on a compassionate use basis through an Expanded Access Program while it seeks FDA approval.

EAP=Expanded Access Program; EMG=electromyography; MFM=motor function measure; MuSK=muscle-specific kinase; SGI=Subject Global Impression.


  • The SGI is a measure of changes in a subject’s perception of change in overall well-being. The patient is asked to use the 7-point scale to rate their impression of the effects of the study medication, during the preceding 3 days on their physical well-being. The 7-point SGI scale: 1=terrible; 2=mostly dissatisfied; 3=mixed; 4=partially satisfied; 5=mostly satisfied; 6=pleased; 7=delighted. 
  • The MFM score evaluates the severity and progression of motor function and monitors weakness in neuromuscular disorders. It is applicable to both ambulant and non-ambulant patients with a wide range of disease severity. The scale exists in 2 versions, one with 32 items for patients aged 6-60 years (MFM-32), the other, with 20 items for children aged 2-6 years (MFM-20). The MFM has 3 functional dimensions: D1, standing position and transfers (13 items, 8 items in the short version); D2, axial and proximal motor function (12 items, 8 in the short version); and D3, distal motor function (7 items, 4 in the short version). A total score is calculated as well as a score for each dimension (data are usually presented as a percentage of normal maximal score).


  1. Engel AG, Shen XM, Selcen D, Sine SM. Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. Lancet Neurol. 2015;14(4):420-434.
  2. Eymard B, Hantaï D, Estournet B. Congenital myasthenic syndromes. Handb Clin Neurol.2013;113:1469-1480.
  3. Ohno K, Ohkawara B, Ito M. Recent advances in congenital myasthenic syndromes. Clin Exp Neuroimmunol. 2016;7(3):246–259.

LEMS Clinical

MuSK-MG Clinical

SMA Clinical

Infantile Spasms