Velmanase alfa

Identification

Summary

Velmanase alfa is a recombinant human lysosomal alpha-mannosidase used to treat non-neurological symptoms of mild to moderate alpha-mannosidosis.

Generic Name

Velmanase alfa

DrugBank Accession Number

DB12374

Background

Velmanase alfa is a recombinant human lysosomal alpha-mannosidase developed for enzyme replacement therapy to treat alpha-mannosidosis. Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder. Patients with alpha-mannosidosis have a genetic mutation that causes a deficiency in the lysosomal enzyme alpha-mannosidase, which is an enzyme responsible for breaking down complex sugars in the body. The resulting accumulation of sugars in the body leads to an array of clinical manifestations leading to progressive neuromuscular and skeletal deterioration, such as skeletal abnormalities, motor function impairment, intellectual disability, and respiratory dysfunction.¹

As long-term enzyme replacement therapy, velmanase alfa supplements or restores the function of deficient alpha-mannosidase. Velmanase alfa has an amino acid sequence of the monomeric protein identical to the naturally occurring human alpha-mannosidase.⁴ It was granted marketing authorization by the European Commission in March 2018 under the market name Lamzede ⁵ as the first human recombinant form of alpha-mannosidase for the treatment of alpha-mannosidosis.¹ In February 2023, the FDA also approved velmanase alfa for the same indication.⁶ Velmanase alfa is currently not approved in Canada.

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Recombinant Enzymes

Protein Chemical Formula

Not Available

Protein Average Weight

Not Available

Sequences

>Sequence
GGYETCPTVQPNMLNVHLLPHTHDDVGWLKTVDQYFYGIKNDIQHAGVQYILDSVISALL
ADPTRRFIYVEIAFFSRWWHQQTNATQEVVRDLVRQGRLEFANGGWVMNDEAATHYGAIV
DQMTLGLRFLEDTFGNDGRPRVAWHIDPFGHSREQASLFAQMGFDGFFFGRLDYQDKWVR
MQKLEMEQVWRASTSLKPPTADLFTGVLPNGYNPPRNLCWDVLCVDQPLVEDPRSPEYNA
KELVDYFLNVATAQGRYYRTNHTVMTMGSDFQYENANMWFKNLDKLIRLVNAQQAKGSSV
HVLYSTPACYLWELNKANLTWSVKHDDFFPYADGPHQFWTGYFSSRPALKRYERLSYNFL
QVCNQLEALVGLAANVGPYGSGDSAPLNEAMAVLQHHDAVSGTSRQHVANDYARQLAAGW
GPCEVLLSNALARLRGFKDHFTFCQQLNISICPLSQTAARFQVIVYNPLGRKVNWMVRLP
VSEGVFVVKDPNGRTVPSDVVIFPSSDSQAHPPELLFSASLPALGFSTYSVAQVPRWKPQ
ARAPQPIPRRSWSPALTIENEHIRATFDPDTGLLMEIMNMNQQLLLPVRQTFFWYNASIG
DNESDQASGAYIFRPNQQKPLPVSRWAQIHLVKTPLVQEVHQNFSAWCSQVVRLYPGQRH
LELEWSVGPIPVGDTWGKEVISRFDTPLETKGRFYTDSNGREILERRRDYRPTWKLNQTE
PVAGNYYPVNTRIYITDGNMQLTVLTDRSQGGSSLRDGSLELMVHRRLLKDDGRGVSEPL
MENGSGAWVRGRHLVLLDTAQAAAAGHRLLAEQEVLAPQVVLAPGGGAAYNLGAPPRTQF
SGLRRDLPPSVHLLTLASWGPEMVLLRLEHQFAVGEDSGRNLSAPVTLNLRDLFSTFTIT
RLQETTLVANQLREAASRLKWTTNTGPTPHQTPYQLDPANITLEPMEIRTFLASVQWKEV
DG

References:

1. KEGG DRUG: Velmanase alfa [Link]

Download FASTA Format

Synonyms

• Lamazym
• Recombinant Human Alpha Mannosidase
• Rhlaman
• Velmanase alfa
• Velmanase alfa-tycv

Pharmacology

Indication

Velmanase alfa is an enzyme replacement therapy for the treatment of non-neurological manifestations in patients with mild to moderate alpha-mannosidosis.^4,6

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Associated Conditions

• Non-neurological symptoms

Contraindications & Blackbox Warnings

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Pharmacodynamics

Velmanase alfa is an enzyme replacement therapy that aims to reduce oligosaccharide levels in patients with alpha-mannosidosis. In clinical trials, reduced serum oligosaccharide levels and improvements in biochemical and functional measures were seen at 18 months ² and for up to four years of treatment.³

Reversing the organ damage or showing improvements in alpha-mannosidosis becomes increasingly difficult as the accumulation of end-organ damage progresses over time. Velmanase alfa has no effects on irreversible complications of the disorder, such as skeletal deformities, dysostosis multiplex, neurological manifestations, and impaired cognitive function.⁴

Mechanism of action

Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder: it is a multi-systemic disease, characterized by a wide range of clinical manifestations including skeletal abnormalities, motor function impairment, intellectual disability, hearing loss, respiratory dysfunction, recurrent infections, and immunodeficiency usually presenting in early childhood. Alpha-mannosidosis is caused by pathogenic sequence variants in the MAN2B1 gene, leading to the deficiency of the lysosomal enzyme, alpha-mannosidase. Alpha-mannosidase is a lysosomal enzyme involved in glycoprotein catabolism. Deficient alpha-mannosidase results in the accumulation of mannose-rich oligosaccharides, causing impaired cellular function and apoptosis in all tissues.^1,2

Velmanase alfa is a recombinant form of human alpha-mannosidase. Upon administration, velmanase alfa supplements or replaces natural alpha-mannosidase to properly break down hybrid and complex high-mannose oligosaccharides in the lysosome, reducing the amount of accumulated mannose-rich oligosaccharides.⁴

Absorption

Following weekly intravenous infusion of 1 mg/kg of velmanase alfa, the mean C_max of 8 µg/mL at steady-state was reached at 1.8 hours after the start of administration.⁴

Volume of distribution

The steady-state volume of distribution is 0.27 L/kg, indicating distribution confined to plasma. It does not cross the blood-brain barrier.⁴

Protein binding

There is no information.

Metabolism

Velmanase alfa is expected to undergo nonspecific degradation into small peptides and subsequently amino acids, similar to other natural occurring proteins.⁴

Route of elimination

There is no information.

Half-life

At the end of intravenous infusion, velmanase alfa plasma concentrations fell in a biphasic fashion with a mean terminal elimination half-life of about 30 hours.⁴

Clearance

The mean clearance of velmanase alfa from plasma is 6.7 mL/h/kg: it is consistent with rapid cellular uptake of velmanase alfa via mannose receptors.⁴

Adverse Effects

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Toxicity

There is no information regarding the LD₅₀ of velmanase alfa.

There is no experience with overdose of velmanase alfa. In clinical studies, a single dose of 100 units/kg (approximately corresponding to 3.2 mg/kg) velmanase alfa led to a mild fever that lasted for five hours in one patient; however, no treatment was necessary.⁴

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Not Available

Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Lamzede	Injection, powder, for solution	10 mg	Intravenous	Chiesi Farmaceutici S.P.A.	2020-12-16	Not applicable
Lamzede	Injection, powder, lyophilized, for solution	10 mg/1	Intravenous	Chiesi USA, Inc.	2023-03-01	Not applicable
Lamzede	Injection, powder, for solution	10 mg	Intravenous	Chiesi Farmaceutici S.P.A.	2020-12-16	Not applicable
Lamzede	Injection, powder, for solution	10 mg	Intravenous	Chiesi Farmaceutici S.P.A.	2020-12-16	Not applicable

Categories

ATC Codes

A16AB15 — Velmanase alfa

• A16AB — Enzymes
• A16A — OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
• A16 — OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
• A — ALIMENTARY TRACT AND METABOLISM

Drug Categories

• Alimentary Tract and Metabolism
• Enzyme Replacement Therapy
• Enzymes
• Enzymes and Coenzymes

Chemical TaxonomyProvided by Classyfire

Description

Not Available

Kingdom

Organic Compounds

Super Class

Organic Acids

Class

Carboxylic Acids and Derivatives

Sub Class

Amino Acids, Peptides, and Analogues

Direct Parent

Peptides

Alternative Parents

Not Available

Substituents

Not Available

Molecular Framework

Not Available

External Descriptors

Not Available

Affected organisms

Not Available

Chemical Identifiers

UNII

M91TG242P2

CAS number

1492823-75-2

References

General References

1. Harmatz P, Cattaneo F, Ardigo D, Geraci S, Hennermann JB, Guffon N, Lund A, Hendriksz CJ, Borgwardt L: Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): Novel global treatment response model and outcomes in patients with alpha-mannosidosis. Mol Genet Metab. 2018 Jun;124(2):152-160. doi: 10.1016/j.ymgme.2018.04.003. Epub 2018 Apr 18. [Article]
2. Borgwardt L, Guffon N, Amraoui Y, Dali CI, De Meirleir L, Gil-Campos M, Heron B, Geraci S, Ardigo D, Cattaneo F, Fogh J, Van den Hout JMH, Beck M, Jones SA, Tylki-Szymanska A, Haugsted U, Lund AM: 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. J Inherit Metab Dis. 2018 Nov;41(6):1215-1223. doi: 10.1007/s10545-018-0185-0. Epub 2018 May 30. [Article]
3. Lund AM, Borgwardt L, Cattaneo F, Ardigo D, Geraci S, Gil-Campos M, De Meirleir L, Laroche C, Dolhem P, Cole D, Tylki-Szymanska A, Lopez-Rodriguez M, Guillen-Navarro E, Dali CI, Heron B, Fogh J, Muschol N, Phillips D, Van den Hout JMH, Jones SA, Amraoui Y, Harmatz P, Guffon N: Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase (velmanase alfa) treatment in patients with alpha-mannosidosis. J Inherit Metab Dis. 2018 Nov;41(6):1225-1233. doi: 10.1007/s10545-018-0175-2. Epub 2018 May 3. [Article]
4. Summary of Product Characteristics: Lamzede (velmanase alfa) solution for intravenous infusion [Link]
5. European Medicines Agency: Lamzede (velmanase alfa) [Link]
6. FDA Approved Drug Products: LAMZEDE (velmanase alfa-tycv) for injection, for intravenous use [Link]

External Links

PubChem Substance

347911328

RxNav

2630725

Wikipedia

Velmanase_alfa

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
3	Completed	Treatment	Alpha-Mannosidosis	4
3	Withdrawn	Treatment	Alpha-Mannosidosis	1
2	Completed	Treatment	Alpha-Mannosidosis	2
2	Unknown Status	Treatment	Alpha-Mannosidosis	1
1	Completed	Treatment	Alpha-Mannosidosis	1
Not Available	Available	Not Available	Alpha-Mannosidosis	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Intravenous	10 mg
Injection, powder, lyophilized, for solution	Intravenous	10 mg/1
Powder, for solution	Intravenous; Parenteral	10 MG

Prices

Not Available

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Not Available

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Drug created at October 20, 2016 22:07 / Updated at April 23, 2023 14:17