Asparagine Depleting Therapies

Asparagine Depleting Therapies – Target Pipeline List 02/2019

Target: Asparagine

This Target Pipeline List provides an overview of isolated and recombinant asparaginase enzymes on the market or in development for treatment of leukemia and solid tumors.

Asparaginase is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid and ammonia. Asparaginase products are isolated from different types of bacteria, namely Escherichia coli and Erwinia chrysanthemi. They inhibit protein synthesis in tumor cells by depriving them of the amino acid asparagine. This drug is phase specific, with the greatest activity in the G1 phase of the cell cycle. Clinical use is confined presently to acute lymphocytic leukemia. Asparaginase products may produce acute hypersensitivity reactions with hypotension, sweating, bronchospasm, and urticaria.

First generation products are isolated from E.coli or Erwinia chrysanthemi. Another formulation of asparaginase is pegaspargase (PEG-l-asparaginase), which has polyethylene glycol covalently linked to the asparaginase structure to decrease immunogenicity and to prolong its half-life.

Next generation asparaginase products and product candidates are produced by recombinant DNA technology and by application of half-life extension technologies. With more than US$ 400 mln in 2017 sales, asparaginase products represent an attractive niche market for biosuperior products as well as for biosimilar versions.

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