Muscle weakness disease LEMS drug 3,4-DAP may get speedier review in US: BioMarin

Lambert Eaton Myasthenic Syndrome is a rare disorder that affects 4-10 in million

BioMarin’s 3,4-diaminopyridine (3,4-DAP), amifampridine phosphate for the treatment of the rare autoimmune disease Lambert Eaton Myasthenic Syndrome (LEMS) has been granted orphan drug designation by US Food and Drug Administration.

Lambert Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disease. LEMS’ presents with  the primary symptoms of weaking muscles.

Patients with LEMS typically present with fatigue, muscle pain and stiffness. The weakness is generally more marked in the proximal muscles particularly of the legs and trunk.

Other symptoms of LEMS include reduced reflexes, drooping of the eyelids, facial weakness and problems with swallowing.

LEMS patients often report a dry mouth, impotence, constipation and feelings of light headedness on standing.

On occasion these problems can be life threatening when the weakness involves respiratory muscles.

A diagnosis of LEMS is generally made on the basis of clinical symptoms, electromyographic testing and the presence of autoantibodies against voltage gated calcium channels.

Muscle weakness in LEMS is caused by autoantibodies to voltage gated calcium channels leading to a reduction in the amount of acetylcholine released from nerve terminals.

The prevalence of LEMS is estimated at four to ten per million, or approximately 2,000 to 5,000 patients in the E.U. and 1,200 to 3,100 patients in the U.S. Approximately 50 percent of LEMS patients diagnosed have small cell lung cancer.

Current treatment of LEMS consist of strategies directed at the underlying malignancy if one is present.

Immunosuppressive agents have been tried but success is limited by toxicity, and difficulty administering the regimens.

A mainstay of therapy has been 3,4-DAP but its use in practice has been limited by the drug’s availability.

3,4-DAP has previously received orphan drug designation in the E.U.

Also, in October 2009, the Committee for Medicinal Products for Human Use of the European Medicines Evaluations Agency adopted a positive opinion recommending approval of amifampridine phosphate for LEMS.

If approved by the European Commission, amifampridine phosphate will be the first approved treatment for LEMS, thereby conferring orphan drug protection and providing ten years of market exclusivity in Europe.

“We look forward to meeting with the FDA in early 2010 to determine the necessary regulatory path for amifampridine phosphate in the U.S,”stated Jean-Jacques Bienaime, Chief Executive Officer of BioMarin.

BioMarin plans to launch the product in Europe in the first quarter of 2010, he said.

BioMarin will also evaluate the best development strategy for amifampridine phosphate in other indications in the U.S. and Europe, as well.

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions.

BioMarin’s  product portfolio comprises three approved products and multiple clinical and pre-clinical product candidates. Approved products include Naglazyme (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin; Aldurazyme (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation; and Kuvan (sapropterin dihydrochloride) tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck KGaA of Darmstadt, Germany.

BioMarin’s other product candidates include PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase), which is currently in Phase II clinical development for the treatment of PKU and GALNS (N-acetylgalactosamine 6-sulfatase), which is currently in Phase I/II clinical development for the treatment of MPS IVA.