Type of information: Granting of a Market Authorisation in the US
Product name: Asparlas® - calaspargase pegol (Cal-PEG - SHP663)
Compound: calaspargase pegol
Therapeutic area: Cancer - Oncology
- enzyme/protein. Calaspargase pegol is an intravenous formulation containing E. coli-derived L-asparaginase II conjugated with succinimidyl carbonate monomethoxypolyethylene glycol (SC-PEG). L-asparaginase hydrolyzes L-asparagine to L-aspartic acid and ammonia, thereby depleting cells of asparagine; asparagine depletion blocks protein synthesis and tumor cell proliferation, especially in the G1 phase of the cell cycle and ultimately induces tumor cell death. Asparagine is critical to protein synthesis in acute lymphoblastic leukemia (ALL) cells which, unlike normal cells, cannot synthesize this amino acid due to the absence of the enzyme asparagine synthase. Pegylation decreases enzyme antigenicity and increases its half life. SC is used as a PEG linker to facilitate attachment to asparaginase and enhances the stability of the formulation.
- Calaspargase pegol was originally developed by Shire. In April 2018, Servier has entered into a definitive agreement with Shire to acquire its Oncology business for $2.4 billion. The transaction covered the transfer of Shire’s oncology business including calaspargase Pegol (CalPEG) and early stage immuno-oncology pipeline collaborations.
Company: Servier Pharmaceuticals (USA), a subsidiary of Servier (France)
Disease: acute lymphoblastic leukemia (ALL)
- • On December 20, 2018, the FDA approved Asparlas® calaspargase pegol-mknl, an asparagine specific enzyme, as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years. Approval was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity above the level of 0.1 U/mL when using calaspargase pegol-mknl, 2500 U/m2 intravenously, every 3 weeks. The pharmacokinetics of calaspargase pegol-mknl were studied when administered in combination with multiagent chemotherapy in 124 patients with B-cell lineage ALL. The most common (incidence ? 10%) grade ? 3 adverse reactions were elevated transaminase, increased bilirubin, pancreatitis, and abnormal clotting studies. In a randomized trial, the safety profile of calaspargase pegol-mknl administered every 3 weeks was similar to that of pegaspargase administered every 2 weeks. The recommended calaspargase pegol-mknl dose is 2,500 units/m2 intravenously administered at a minimum dosing interval of every 21 days.
- • On February 28, 2018, Shire announced that the FDA has accepted the Biologics License Application (BLA) for calaspargase Pegol (Cal-PEG; SHP663). The investigational-stage compound is being reviewed as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL). The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of December 22, 2018 for Cal-PEG.
- Shire is developing SHP663 based on more than a decade of data, research and experience with Oncaspar® (pegaspargase), which is approved in the United States as a first-line treatment for patients with ALL.
- Cal-PEG is thought to be based on plasma L-asparagine depletion. The totality of the clinical trial data submitted to the FDA for review, as part of the BLA, included a comparable safety profile and efficacy outcomes to Oncaspar®.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2018-12-20
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: