LAMZEDE (velmanase alfa-tycv)

LAMZEDE (velmanase alfa-tycv)

Office-Administration – intravenous (IV) infusion

Diagnosis considered for coverage:

Alpha–Mannosidosis: Indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients. 

Coverage Criteria:

For diagnosis of alpha-mannosidosis (AM):

• Diagnosis of alpha-mannosidosis; AND
• Disease is confirmed by one of the following:
  • Deficiency in alpha-mannosidase enzyme activity as measured in fibroblasts or leukocytes
  • Molecular genetic testing confirms mutations in the MAN2B1 gene; AND
• Treatment is only for non-central nervous system disease manifestations (e.g., large head, prominent forehead, protruding jaw, skeletal abnormalities).

Reauthorization Criteria:

For diagnosis of AM:

• Patient does not show evidence of progressive disease while on therapy as evidenced by one of the following:
  • Reduction in serum oligosaccharide concentration from baseline
  • Improvement in clinical signs and symptoms from baseline (e.g., 3-minute stair climbing test, 6-minute walking test, pulmonary function, quality of life).

Dosing:

• 1 mg/kg (actual body weight) administered once every week as an intravenous (IV) infusion.

Coverage Duration:

• 1 year

Authorization is not covered for the following:

• The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information:

• AM is a rare autosomal recessive lysosomal storage disorder that is characterized by deficiency of the lysosomal enzyme, alpha-mannosidase. This deficiency can lead to facial and skeletal abnormalities, hearing impairment, intellectual disability, and immune deficiency.
• Three clinical types of AM have been described in the literature:
  • Type 1, which is a mild form, is clinically recognized after 10 years of age, without skeletal abnormalities and very slow progression.
  • Type 2, the most common type, is a moderate form, clinically recognized before 10 years of age, with skeletal abnormalities and slow progression with development of ataxia at age 20 to 30 years.
  • Type 3, a severe form, which is immediately recognized, with skeletal abnormalities and obvious progression, leading to an early death from primary central nervous system (CNS) involvement or myopathy.
• Lamzede (velmanase alfa-tycv; hereafter referred to as velmanase), the first enzyme replacement therapy (ERT) for the treatment of AM. The FDA granted velmanase orphan drug designation in February 2006, rare pediatric disease designation in December 2018, and Fast Track designation in December 2019. Lamzede was FDA-approved in February 2023.
• There is a boxed warning for hypersensitivity reactions, including anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs, velmanase should be discontinued immediately and appropriate medical treatment should be initiated.

Policy Updates:

• 09/01/2023 – New program for Lamzede approved by P&T (P&T 08/15/2023).

References:

1. Lamzede Prescribing Information. Chiesi USA, Inc. Cary, NC. February 2023.
2. ClinicalTrials.gov. A Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01681953?term=nct01681953&draw=2&rank=1. Accessed June 29, 2023.
3. ClinicalTrials.gov. Trial on Safety and Efficacy of Velmanase Alfa Treatment in Pediatric Patients With Alpha-Mannosidosis (rhLaman-08). Available at: https://www.clinicaltrials.gov/ct2/show/NCT02998879?term=NCT02998879&draw=2&rank=1. Accessed June 29, 2023.
4. Bordwardt, L., Guffon, N., et al. Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial. Avaiable at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326984/. Accessed June 29, 2023.
5. Malm, D, Nilssen, O. Alpha-Mannosidosis. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1396/. Accessed June 29, 2023.
6. Alpha Mannosidosis. Available at: https://rarediseases.org/rare-diseases/alpha-mannosidosis/. Accessed June 29, 2023.