Ligand Pharmaceuticals Incorporated announced that its partner Jazz Pharmaceuticals plc has been granted marketing authorization by the European Commission (EC) for Enrylaze® (JZP458; a recombinant Erwinia asparaginase or crisantaspase) for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients (one month and older) who have developed hypersensitivity or silent inactivation to E. coli-derived asparaginase. Enrylaze, approved as Rylaze® in the United States and Canada, is a new Erwinia-derived asparaginase developed using a next-generation recombinant technology with a safety profile consistent with that of other asparaginase preparations.
“We congratulate our partner Jazz on its receipt of approval for Enrylaze® from the European Commission, expanding the market opportunity for one of our key commercial-stage products,” said Todd Davis, CEO of Ligand Pharmaceuticals. “Jazz has executed on a successful launch of the product in the U.S., and we look forward to contributions from sales in the European Union.”
Ligand is eligible to receive milestone payments and tiered low- to mid-single digit royalties based on worldwide net sales of any products resulting from its collaboration with Jazz, including Rylaze.
Enrylaze may be given by both intravenous infusion (IV) and intramuscular injection (IM) and is dosed either on alternate days (every 48 hours) or via a Monday/Wednesday/Friday (MWF) dosing schedule. The use of recombinant technology to manufacture Enrylaze delivers a scalable supply – able to meet global demand, and a ready-to-use solution that avoids the need for reconstitution in the clinic.
The EC approval is based on data from a Phase 2/3 trial conducted in collaboration with the Children’s Oncology Group (COG) in a cohort of 228 pediatric and adult patients with ALL and LBL who have developed hypersensitivity or silent inactivation to E. coli-derived asparaginase. The study was conducted in two parts to assess the IV and IM routes of administration. The determination of efficacy was based on demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) levels ≥ 0.1 U/mL.
The study showed that for the IV administration of JZP458 (a recombinant Erwinia asparaginase or crisantaspase) (25/25/50 mg/m2 MWF), the proportion of patients maintaining NSAA ≥ 0.1 U/mL at 48 hours after a dose was 89.8% (95% CI: 82.1%, 97.5%) and 40% at 72 hours post-dose (95% CI: 26.4%, 53.6%). The IM administration of JZP458 (25/25/50 mg/m2 MWF) achieved sustained asparagine activity in 95.9% of patients at 48 hours after a dose (95% CI: 90.4%, 100.0%) and 89.8% of patients at 72 hours post-dose (95% CI: 81.3%, 98.3%). The other dosing schedules were based on interpolation from pharmacokinetic (PK) and response rates observed with the very similar investigated regimens.
Overall, the safety profile of JZP458 was consistent with the reported safety information for patients with ALL/LBL receiving asparaginase with combination chemotherapy. The most common adverse reactions were anemia, vomiting, thrombocytopenia, neutropenia, nausea, febrile neutropenia, fatigue, pyrexia, decreased appetite, transaminase increased, abdominal pain, white blood cell count decreased, headache, diarrhea, and lymphocyte count decreased. The most frequent serious adverse reactions were febrile neutropenia, pyrexia, vomiting, sepsis, medicinal product hypersensitivity, nausea, and pancreatitis.
The European Commission approval extends to all European Union Member states, as well as Iceland, Norway, and Liechtenstein.
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