FDA Approves First Enzyme Replacement Therapy for α-Mannosidosis
Lamzede helps break down oligosaccharides and prevents their accumulation in patients with this rare disease
FDA has approved Lamzede (velmanase alfa), the first enzyme replacement therapy approved in the US, for treating the noncentral 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 10 mg injection once every week.
What is alpha-mannosidosis?
Alpha-mannosidosis is a rare genetic lysosomal storage disorder, affecting about one in every 500,000 people worldwide. 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
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.
Efficacy of Lamzede: Phase 3 trial
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 one 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. Some 15 patients (eight adult and seven pediatric) received Lamzede and 10 patients (five adult and five pediatric) received a placebo.
The efficacy results for the clinical endpoints assessed at 12 months—three-minute stair climbing test, six-minute walking test, and forced vital capacity—all favored the Lamzede group and were supported by a reduction in serum oligosaccharide concentration.
Safety Information
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, Lamzede is to be discontinued immediately and appropriate medical treatment is to be initiated. In patients with a severe hypersensitivity reaction, health care professionals may consider a desensitization procedure to Lamzede.
Lamzede received orphan drug designation for this indication.
- This news release was originally published on the U.S. Food & Drug Administration website