FDA approves first enzyme replacement therapy for rare alpha-mannosidosis
FDA has approved Lamzede (velmanase alfa), the first enzyme replacement therapy approved in the U.S. for the treatment of the non-central nervous system manifestations of alpha-mannosidosis, a rare genetic condition characterized by the lack of the alpha-mannosidase enzyme in the body. Lamzede acts the same way as the alpha-mannosidase enzyme in the human body thus restoring normal cellular activity in patients. Patients receive Lamzede as a 10mg injection once every week.
Disease or Condition
Alpha-mannosidosis is a rare genetic lysosomal storage disorder. The symptoms of the disorder vary, but often include mild to moderate intellectual disability, hearing loss, weakened immune system, distinctive facial features (e.g., a large head, prominent forehead, and protruding jaw), skeletal abnormalities, and muscle weakness. Alpha-mannosidosis is caused by genetic changes in the MAN2B1 gene, which codes for the lysosomal alpha-mannosidase enzyme. Mutations of the MAN2B1 gene result in the lack of production of the alpha-D-mannosidase enzyme or the production of a defective, inactive form of the enzyme. Alpha-mannosidosis affects about 1 in every 500,000 people worldwide.
Lamzede’s effectiveness was evaluated in adults and pediatric patients with alpha-mannosidosis in a phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel group study. The trial evaluated Lamzede’s efficacy over 52 weeks at a dose of 1 mg/kg given weekly as an intravenous infusion. A total of 25 patients were enrolled (14 males, 11 females), including 13 adult patients (age range: ≥18 to 35 years; mean: 25 years) and 12 pediatric patients (age range: ≥6 to <18 years; mean: 11 years); all patients were White. Fifteen patients (8 adult and 7 pediatric) received Lamzede and 10 patients (5 adult and 5 pediatric) received placebo.
The efficacy results for the clinical endpoints assessed at 12 months, 3-minute stair climbing test, 6-minute walking test, and forced vital capacity, all favored the Lamzede group and were supported by a reduction in serum oligosaccharide concentration.
The most common adverse reactions to Lamzede are hypersensitivity reactions including anaphylaxis, a severe, potentially life-threatening allergic reaction. Appropriate medical support measures, including resuscitation equipment, should be readily available during Lamzede administration. If a severe hypersensitivity reaction occurs, discontinue Lamzede immediately and initiate appropriate medical treatment. In patients with severe hypersensitivity reaction, health care professionals may consider a desensitization procedure to Lamzede.
Lamzede received orphan drug designation for this indication.