L-asparaginase (L-ASNase)

Modality

Therapeutic Use of L-asparaginase (L-ASNase)

Decreased asparagine (Asn) level leads to increased cytotoxicity against leukaemia cells and improved outcomes for patients with acute lymphoblastic leukaemia (ALL). As an enzyme specific for asparagine digestion, L-asparaginase (L-ASNase) catalyzes the conversion of L-asparagine to ammonia and L-aspartate, and therefore is clinically approved as antitumor therapeutic for treating ALL.

The production of L-asparaginase using microorganisms has aroused great interest due to its cost-effectiveness and eco-friendliness. Several native and recombinant L-ASNase, including Pegaspargase (Oncaspar), Asparaginase (Elspar), Calaspargase Pegol (Asparlas), Asparaginase (Spectrila), and Asparaginase erwinia chrysanthemi Rylaze/Enrylaze, have been approved as enzyme replacement therapies for ALL.

Native Microbial L-asparaginase

Pegaspargase (Oncaspar)

A pegylated L-asparaginase, Pegaspargase (Oncaspar), can catalyze the transformation of the amino acid L-asparagine into aspartic acid and ammonia. In detail, pegaspargase is a native L-asparagine amidohydrolase produced in endogenously Escherichia coli (E. coli). L-asparaginase is a homo-tetrameric enzyme, the subunit of which has a molecule weight of 34.5 kDa.

Asparaginase (Elspar)

Another E. coli-derived L-asparagine amidohydrolase (type EC-2) was developed by Merck and approved by FDA with the generic name Asparaginase and trade name Elspal. It was later licensed to Lundbeck.

Calaspargase Pegol (Asparlas)

Calasparagase Pegol (Asparlas) is an E. coli derived L-asparaginase conjugated by polyethylene glycol monomethanol (mPEG) carrying a succinimidyl carbonate (SC) linker.

The PEG in Calaspargase Pegol has the same size as the current commercially available PEG asparaginase (Oncaspar), while Calaspargase Pegol includes a new ligand with a higher hydrolytic stability and higher biological activity. Pegaspargase (Oncaspar) and Calaspargase Pegol (Asparlas) are developed and commercialized by Servier.

Recombinant L-asparaginase

Asparaginase (Spectrila)

The first recombinant asparaginase, Asparaginase (Spectrila), was developed by Medac SrL and received marketing authorization from the EMA in 2016. The recombinant asparaginase as an active substance is produced in E. coli and shares identical amino acid sequence and enzymatic activity with natural E. coli derived asparaginase.

Asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze/ Enrylaze)

The active substance of Asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze/ Enrylaze) is called recombinant L-asparaginase, a homo-tetrameric enzyme. Rylaze is generated though fermentation of a genetically engineered Pseudomonas fluorescens bacterium. The host strain contains asparaginase coding gene from Erwinia chrysanthemi (chrysanthemum). The amino acid sequence of recombinant L-asparaginase is identical to native Erwinia chrysanthemi asparaginase. Developed by Jazz Pharmaceuticals, Rylaze is licensed for the management of patients who are hypersensitivity to asparaginase produced in E. coli.

Yaohai Bio-Pharma Offers One-Stop CDMO Solution for L-asparaginase

L-asparaginase Pipeline

Generic Name	Brand Name/ Altermative Name	Expression System	Indications	Manufacturer	R&D Stage
Calaspargase Pegol-MKNL	ASPARLAS, Cal-PEG, calaspargase pegol-mknl, SHP-663	native, E. coli-derived	Acute lymphoblastic leukemia (ALL)	Servier	Approval
Pegaspargase	Asparaginase macrogol, Oncaspar	native, E. coli-derived	Acute lymphoblastic leukemia (ALL)	Servier	Approval
Asparaginase	Elspar	native, E. coli-derived	Acute lymphoblastic leukemia (ALL)	Merck & Co., Inc.	Approval
Asparaginase	Spectrila, Recombinant Asparaginase	E. coli	Acute lymphoblastic leukemia (ALL)	Medac SrL	Approval
Crisantaspase	Rylaze, Enrylaze, Recombinant Asparaginase	Pseudomonas fluorescens	Acute lymphoblastic leukemia (ALL), hypersensitivity to E. coli derived asparaginase	Jazz Pharmaceuticals	Approval
L-asparaginase	Leunase, KW-020	Pending Update	Acute lymphoblastic leukemia (ALL)	Kyowa Kirin	Approval
L-asparaginase	L-Asparaginase Biosimilar	Pending Update	Acute lymphoblastic leukemia (ALL)	Laboratorios Bioprofarma	Approval
L-asparaginase	L-Asparaginase Biosimilar	Pending Update	Acute lymphoblastic leukemia (ALL)	Chandra Bhagat Pharma Ltd.	Approval
L-asparaginase	Pegaspargase biosimilar	Pending Update	Acute lymphoblastic leukemia (ALL)	Gennova, Emcure	Approval

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L-asparaginase (L-ASNase)

Modality