FDA Approves First Enzyme Replacement Therapy for α-Mannosidosis

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