Breakthrough Therapy Designation for Firdapse to treat Lambert-Eaton Myasthenic Syndrome (LEMS)

· TGI - Cancer, TGI - Health, Uncategorized

Recently, Catalyst Pharmaceutical Partners Received Breakthrough Therapy Designation From FDA for Firdapse(TM) for the Treatment of LEMS.

Company announced that its investigational product Firdapse(TM) (amifampridine phosphate) has received “Breakthrough Therapy Designation” by the U.S. Food and Drug Administration (FDA) for the symptomatic treatment of patients with Lambert-Eaton Myasthenic Syndrome (LEMS). Firdapse(TM) is Catalyst’s investigational therapy that is being evaluated for the treatment of the debilitating symptoms associated with LEMS, including muscle weakness.

“We are very pleased to have received Breakthrough Therapy Designation for Firdapse(TM) and we are excited by the FDA’s decision to place our product in a category that may enable expedited development and review for patients with LEMS,” said Patrick McEnany, President and Chief Executive Officer of Catalyst. “With no approved or effective symptomatic treatment currently available for LEMS, Firdapse(TM) has the potential to be the first-line treatment option for patients with this rare condition.”

Breakthrough Therapy Designation for Firdapse(TM) was based on clinical data from several previously published clinical trials of amifampridine (3,4-DAP) in patients with LEMS. Firdapse(TM) has the potential to provide significant relief of the often debilitating symptoms of the disease, including muscle weakness (e.g. difficulty walking), difficulty swallowing and talking, drooping of eyelids and facial weakness. Read more at source.

Lambert-Eaton Myasthenic Syndrome, LEMS:

LEMS is a rare autoimmune disease that can be severely disabling, with the primary symptom of muscle weakness.  The weakness is generally more marked in the proximal muscles, particularly of the legs and trunk,  this leads to difficulties climbing stairs and rising from a sitting position. Physical exercise and high temperatures can worsen the symptoms.  In the advanced stages of the disease, weakness of the respiratory muscles may occur.  Some may also experience problems with coordination (ataxia). ( People who develop LEMS are usually over 40, although it may occur at any age.

Other problems include:

  • reduced reflexes,
  • drooping of the eyelids,
  • facial weakness and
  • problems with swallowing.
  • dry mouth,
  • impotence,
  • constipation and
  • feelings of light headedness on standing.

These problems can be life threatening when the weakness involves respiratory muscles.

The prevalence of LEMS is estimated at approximately 3,000 patients in the United States and Canada. Approximately 50 percent of LEMS patients diagnosed have small cell lung cancer. Patients with LEMS typically present with fatigue, muscle pain and stiffness.


The muscle weakness in LEMS is caused by autoantibodies to voltage gated calcium channels, which cause a reduction in the amount of acetylcholine released from nerve terminals. LEMS is often associated with lung cancer (50–70%), making LEMS a paraneoplastic syndrome.

Non-small-cell lung carcinoma

Of the people with small cell lung cancer, 1–3% have LEMS. In most of these cases, LEMS is the first symptom of the lung cancer, and it is otherwise asymptomatic. LEMS may also be associated with autoimmune diseases, such as hypothyroidism (an underactive thyroid gland) or diabetes mellitus type 1.


Review: Brain Nerve. 2010 Apr;62(4):419-26

Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular disorder in which autoantibodies inhibit the presynaptic release of acetylcholine. Autoantibodies against P/Q-type voltage-gated calcium channels (VGCC) are detected in 85% of patients with LEMS. In addition, autoantibodies to synaptotagmin, an M1-type muscarinic acetylcholine receptor and SOX1 are also found in the sera of patients with LEMS. LEMS is closely associated with small cell lung cancer (SCLC) in 50-60% of patients, it is therefore regarded as a paraneoplastic syndrome (a condition that arises as a result of cancer elsewhere in the body). And the other half of the patients have an idiopathic form of the disease.

Patients with SCLC who have anti-VGCC antibodies have been reported to have a favorable prognosis. In contrast to paraneoplatic LEMS, other forms of LEMS may have an autoimmune aspect because of the established association between human leukocyte antigen and a family history of other autoimmune disorders in this condition.

The clinical features of LEMS include proximal weakness, areflexia, ptosis, cerebellar ataxia and autonomic dysfunction.

The findings of electrophysiological examination show that LEMS is characterized by compound muscle action potential potentials with a low amplitude and increment upon repetitive nerve stimulation at a high rate. Tumor removal is the primary treatment of LEMS.

The efficacy of 3,4-diaminopyridine for the treatment of LEMS has also been established. Patients with LEMS require the immunotherapies such as plasma exchange and the administration of high doses of immunoglobulin and prednisolone.


A diagnosis of LEMS is generally made on the basis of

  • clinical symptoms,
  • electromyographic and
  • compound muscle action potential (CMAP) testing,
  • the presence of autoantibodies against voltage gated calcium channel


 If the disease is associated with cancer, direct treatment of the cancer often relieves the symptoms of LEMS. Other treatments often used are steroids, azathioprine and intravenous immunoglobulin, which suppress the immune system, and pyridostigmine and 3,4-diaminopyridine, which enhance the neuromuscular transmission. Occasionally, plasma exchange is required to remove the antibodies.

Recent literature on treatment:

Treatment for Lambert-Eaton myasthenic syndrome: Cochrane Database Syst Rev. 2011 Feb 16;(2):CD003279. doi: 10.1002/14651858.CD003279.pub3.


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