New Therapy Approved by FDA for Alpha-Mannosidosis
Velmanase alfa-tycv (Lamzede; Chiesi Global Rare Diseases, Boston, MA) has been approved by the Food and Drug Administration (FDA) as the first enzyme replacement therapy in the United States to treat non-central nervous system symptoms associated with alpha-mannosidosis (AM) in adult and pediatric patients. Recommended dosage for velmanase alfa-tycv is 1 mg/kg (actual body weight) administered once weekly as an intravenous infusion. The prescribing information contains a black box warning for severe hypersensitivity reactions; additional recommendations are for clinicians to verify that patients are not pregnant and to consider pretreatment with antihistamines, antipyretics, and/or corticosteroids.
The approval was based on efficacy and safety data from multiple clinical trials including a phase 3 study (NCT01681953) and a phase 2 trial (NCT02998879). The phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group study aimed to evaluate the safety and effectiveness of velmanase alfa-tycv in adult (n=13) and pediatric (n=12) participants over 52 weeks. In the intent-to-treat cohort, participants (n=15) received 1 mg/kg of velmanase alfa-tycv weekly as an intravenous infusion, while the other cohort (n=10) received a placebo. The intent-to-treat cohort had a reduced serum oligosaccharide concentration and performed better on the 3-minute stair climbing test, 6-minute walking test, and forced vital capacity testing at 12 months. Severe hypersensitivity reactions, including anaphylaxis, were the most common adverse event associated with the therapy.
According to Giacomo Chiesi, head of Chiesi Global Rare Diseases, “Lamzede is the first and only enzyme replacement therapy approved for alpha-mannosidosis in the United States, an achievement based on years of clinical development, as well as the dedication of our employees, clinicians, patients, and their families.”
An estimated 1 in every 500,000 to 1,000,000 individuals are affected by this progressive, genetic disease worldwide. This disease causes reduced production of an alpha-D-mannosidase enzyme or an inactivated form of the enzyme to be produced. Without this enzyme, the body is unable to break down complex sugars, which causes muscle weakness, skeletal changes, weakened immune systems, and intellectual disabilities.