FDA Drug Approvals: Pediatrics — Year in Review 2018

Mary L Windle, PharmD


January 15, 2019

New Drugs in Oncology and Hematology

Asparlas (calaspargase pegol)

Calaspargase pegol catalyzes conversion of L-asparagine into aspartic acid and ammonia. The pharmacological effect is thought to be based on selective killing of leukemic cells because of depletion of plasma L-asparagine. It is indicated as part of a multiagent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients aged 1 month to 21 years. Calaspargase pegol provides a longer interval between doses and has an extended shelf-life beyond that of current pegylated asparaginase products.

Approval was based on demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above 0.1 U/mL when using a dose of 2500 U/m2 given intravenously every 3 weeks. The pharmacokinetics were studied in a cohort of 124 patients with B-cell lineage ALL who were a median age of 11.5 years (range, 1-26 years). (Medscape Medical News. December 21, 2018)

Elzonris (tagraxofusp)

Tagraxofusp, a CD123-directed cytotoxin, is indicated for blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and children aged 2 years or older.

Approval was based on results from a multicenter, multicohort, open-label, single-arm clinical trial of 47 patients with BPDCN. Within this cohort, 32 patients were treatment naive and 15 patients had been previously treated. Tagraxofusp was administered on days 1 to 5 of a 21-day cycle for multiple consecutive cycles. The trial was divided into three stages: stage 1 (lead-in, dose escalation), stage 2 (expansion), and stage 3 (pivotal, confirmatory). Patients were also enrolled in an additional cohort (stage 4) to enable uninterrupted access to the drug.

In the stage 3 (pivotal) cohort, 13 patients with treatment-naive BPDCN were treated, and efficacy was based on the rate of complete response or clinical complete response (CR/CRc), with CRc defined as CR with residual skin abnormality not indicative of active disease. The CR/CRc rate was 53.8% (7 of 13), and the median duration of CR/CRc was not reached (range, 3.9-12.2 months). (Stemline)

Vitrakvi (larotrectinib)

Larotrectinib is a tyrosine kinase (TRK) inhibitor that is indicated for adults and children with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or for which surgical resection is likely to result in severe morbidity, and have no alternative treatments or have progressed following treatment.

Chromosomal fusion of TRK has been identified among a wide variety of solid tumors that occur in adults and children. TRK fusions have been shown to activate chimeric proteins, which act as an oncogenic driver by promoting cell proliferation and survival in tumor cell lines.

Approval of larotrectinib was based on clinical trial results of 55 patients aged 4 months to 76 years. Seventeen unique TRK fusion–positive tumor types were represented across the study. The overall response rate was 75% according to independent review and 80% according to investigator assessment. At 1 year, 71% of the responses were ongoing and 55% of the patients remained progression free. (N Engl J Med. 2018 Feb 22;378(8):731-739)

Gamifant (emapalumab)

Emapalumab is indicated for patients with primary hemophagocytic lymphohistiocytosis (HLH) who have refractory, recurrent, or progressive disease, or who are intolerant to conventional HLH therapy. It is a human monoclonal antibody that binds to and neutralizes interferon-gamma, which is thought to be hypersecreted in patients with HLH.

Approval was based on a phase 2/3 trial of 27 patients with refractory, recurrent, or progressive HLH. Results showed 63% achieved a complete response, a partial response, or HLH improvement with emapalumab plus dexamethasone. Additionally, 70% of trial participants were able to continue on to hematopoietic stem cell transplantation. (Medscape Medical News. November 20, 2018)


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