Olipudase alfa

Identification

Summary

Olipudase alfa is a recombinant human acid sphingomyelinase used to treat Acid Sphingomyelinase Deficiency (ASMD) in children and adults.

Generic Name

Olipudase alfa

DrugBank Accession Number

DB12835

Background

Olipudase alfa is recombinant human acid sphingomyelinase.¹ It is the first and only enzyme replacement therapy in the world for the treatment of Acid Sphingomyelinase Deficiency (ASMD), also known as Niemann–Pick disease.⁶ ASMD is a rare lysosomal storage disease caused by mutations in the SMPD1 gene, leading to a deficiency in acid sphingomyelinase and the abnormal accumulation of the primary ASM substrate, sphingomyelin.³ Olipudase alfa works to hydrolyze sphingomyelin accumulated in body tissues, such as the lungs, liver, spleen, kidneys, and bone marrow.¹

Olipudase alfa gained its first global approval in Japan on March 28, 2022.¹ It was later approved by the European Commission on June 28, 2022 ⁶ and by the FDA on August 31, 2022.⁸

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Other protein based therapies

Protein Chemical Formula

C₂₉₀₀H₄₃₇₃N₇₈₃O₇₉₁S₂₄

Protein Average Weight

63590.933 Da (exact)

Sequences

>Olipudase alfa sequence
HPLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNVARVGSVAIKL
CNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISLP
TVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRP
GAGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDQLRALTTV
TALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEALR
TLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDK
VHIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVA
FLAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYRA
RETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLSA
RADSPALCRHLMPDGSLPEAQSLWPRPLFC

References:

1. KEGG DRUG: Olipudase alfa [Link]

Download FASTA Format

Synonyms

• Olipudase alfa

External IDs

• Gz402665

Pharmacology

Indication

Olipudase alfa is indicated as an enzyme replacement therapy for the treatment of non-Central Nervous System manifestations of Acid Sphingomyelinase Deficiency (ASMD) in pediatric and adult patients with type A/B or type B.^5,7

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Associated Conditions

• Acid Sphingomyelinase Deficiency (ASMD)

Contraindications & Blackbox Warnings

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Pharmacodynamics

Olipudase alfa is an enzyme replacement therapy that works to ameliorate the signs and symptoms of ASMD by reducing the amount of sphingomyelin that accumulates in organs and causes tissue damage in patients with ASMD.⁵ It works to reduce the extent of non-neurological manifestations of ASMD, such as splenomegaly and hepatomegaly.⁴

Mechanism of action

ASMD is an autosomal recessive genetic disorder caused by different mutations in the SMPD1 gene that encodes acid sphingomyelinase. Historically, ASMD has been called Niemann-Pick disease (NPD), with different classifications based on disease onset and severity.³ NPD type A (NPD-A) refers to the severe early-onset form, infantile neurovisceral ASMD and NPD type B (NPD-B) is referred to as the later-onset, chronic visceral form of ASMD. Chronic neurovisceral ASMD (NPD-A/B) is a phenotype with intermediate severity.² ASMD has a broad spectrum of disease severity and neurological and non-neurological manifestations; thus, it is difficult to classify different types of ASMD using the former classification system of ASMD (A, B, A/B).³ Acid sphingomyelinase typically breaks down metabolically-related lipids such as sphingomyelin in various cell types, such as the monocytes, macrophages, and hepatocytes.³ The deficiency of acid sphingomyelinase thus leads to the accumulation of these lipids in body tissues, causing progressive cell and tissue damage and impairing organ functioning.³ Olipudase alfa is recombinant human acid sphingomyelinase that hydrolyzes sphingomyelin (SM), preventing its accumulation in body organs. As an enzyme replacement therapy, it is an exogenous source of acid sphingomyelinase.⁵

Absorption

After administration of 3 mg/kg olipudase alfa once every two weeks in adults with ASMD, the mean (percent coefficient of variation, CV%) maximum concentration (C_max) and area under the concentration-time curve over a dosing interval (AUC_0-τ) at steady state were 30.2 µg/mL (17%) and 607 µg.h/mL (20%), respectively.⁵

Volume of distribution

After administration of 3 mg/kg olipudase alfa once every two weeks in adults with ASMD, the estimated mean (CV%) volume of distribution of olipudase alfa is 13.1 L (18%). Olipudase alfa is not expected to cross the blood-brain barrier or modulate the CNS manifestations of the disease.⁵

Protein binding

There is no information available.

Metabolism

Olipudase alfa is a recombinant human enzyme and is expected to be eliminated via proteolytic degradation into small peptides and amino acids.⁵

Route of elimination

There is no information available.

Half-life

After administration of 3 mg/kg olipudase alfa once every two weeks in adults with ASMD, the mean terminal half-life (t1/2) ranged from 31.9 to 37.6 hours.⁵

Clearance

After administration of 3 mg/kg olipudase alfa once every two weeks in adults with ASMD, the mean (CV%) clearance of olipudase alfa is 0.331 L/h (22%).⁵

Adverse Effects

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Toxicity

There is no information available regarding LD₅₀ and overdose of olipudase alfa. There is no known specific antidote for olipudase alfa overdose.

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
Xenpozyme	Injection, powder, for solution	20 mg	Intravenous	Sanofi B.V.	2022-08-02	Not applicable
Xenpozyme	Injection, powder, lyophilized, for solution	4 mg/1.1mL	Intravenous	Genzyme Corporation	2022-08-29	Not applicable
Xenpozyme	Injection, powder, for solution	4 mg	Intravenous	Sanofi B.V.	2023-05-04	Not applicable
Xenpozyme	Injection, powder, for solution	20 mg	Intravenous	Sanofi B.V.	2022-08-02	Not applicable
Xenpozyme	Injection, powder, lyophilized, for solution	20 mg/5.1mL	Intravenous	Genzyme Corporation	2022-08-29	Not applicable
Xenpozyme	Injection, powder, for solution	4 mg	Intravenous	Sanofi B.V.	2023-05-04	Not applicable
Xenpozyme	Injection, powder, for solution	20 mg	Intravenous	Sanofi B.V.	2022-08-02	Not applicable
Xenpozyme	Injection, powder, for solution	20 mg	Intravenous	Sanofi B.V.	2022-08-02	Not applicable
Xenpozyme	Injection, powder, for solution	4 mg	Intravenous	Sanofi B.V.	2023-05-04	Not applicable

Categories

ATC Codes

A16AB25 — Olipudase 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
• Amino Acids, Peptides, and Proteins
• Enzyme Replacement Therapy
• Enzymes
• Enzymes and Coenzymes
• Esterases
• Hydrolases
• Phosphoric Diester Hydrolases
• Proteins
• Recombinant Proteins

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

6D5766Q4OP

CAS number

927883-84-9

References

General References

1. Keam SJ: Olipudase Alfa: First Approval. Drugs. 2022 Jun;82(8):941-947. doi: 10.1007/s40265-022-01727-x. [Article]
2. Wasserstein MP, Schuchman EH: Acid Sphingomyelinase Deficiency . [Article]
3. McGovern MM, Avetisyan R, Sanson BJ, Lidove O: Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD). Orphanet J Rare Dis. 2017 Feb 23;12(1):41. doi: 10.1186/s13023-017-0572-x. [Article]
4. Diaz GA, Jones SA, Scarpa M, Mengel KE, Giugliani R, Guffon N, Batsu I, Fraser PA, Li J, Zhang Q, Ortemann-Renon C: One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. Genet Med. 2021 Aug;23(8):1543-1550. doi: 10.1038/s41436-021-01156-3. Epub 2021 Apr 19. [Article]
5. EMA Approved Drug Products: Xenpozyme (olipudase alfa) Intravenous Infusion [Link]
6. GlobeNewswire News Release: Xenpozyme® (olipudase alfa) approved by European Commission as first and only treatment for ASMD [Link]
7. FDA Approved Drug Products: XENPOZYME (olipudase alfa-rpcp) for injection, for intravenous use [Link]
8. FDA NEWS RELEASE: FDA Approves First Treatment for Acid Sphingomyelinase Deficiency, a Rare Genetic Disease [Link]

External Links

PubChem Substance

347911391

RxNav

2610407

Wikipedia

Olipudase_alfa

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Active Not Recruiting	Treatment	Sphingomyelin Lipidosis	1
2, 3	Active Not Recruiting	Treatment	Sphingomyelin Lipidosis	1
1	Completed	Treatment	Acid Sphingomyelinase Deficiency (ASMD)	1
1, 2	Completed	Treatment	Sphingomyelin Lipidosis	1
Not Available	Approved for Marketing	Not Available	Sphingomyelin Lipidosis	1
Not Available	Recruiting	Not Available	Acid Sphingomyelinase Deficiency (ASMD)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Intravenous	20 mg
Injection, powder, for solution	Intravenous	4 mg
Injection, powder, lyophilized, for solution	Intravenous	20 mg/5.1mL
Injection, powder, lyophilized, for solution	Intravenous	4 mg/1.1mL

Prices

Not Available

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Not Available

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Drug created at October 21, 2016 00:36 / Updated at December 01, 2022 11:27