FDA Approves First-Ever Drug for Rare Cancer

Roxanne Nelson, RN, BSN

December 21, 2018

The US Food and Drug Administration (FDA) has approved tagraxofusp-erzs (Elzonris, Stemline Therapeutics) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients aged 2 years and older. This approval marks the first treatment ever approved for BPDCN.

BPDCN is a clinically aggressive rare disease with a proclivity for skin and leukemic involvement, and currently, there is no consensus regarding optimal treatment modalities. BPDCN more commonly occurs in males, and although it is more frequently diagnosed in older patients, it can develop at any age, including in children.

"Prior to today's approval, there had been no FDA approved therapies for BPDCN," said Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products at the FDA's Center for Drug Evaluation and Research, in a statement. "The standard of care has been intensive chemotherapy followed by bone marrow transplantation."

As many patients with BPDCN are unable to tolerate this intensive therapy, there is an urgent need for alternative treatment options, Pazdur added.

Tagraxofusp is a targeted therapy directed at the interleukin-3 (IL-3) receptor (CD123), a cell surface receptor expressed on a range of malignancies, and is a recombinant fusion protein that links IL-3 to a truncated diphtheria toxin (DT) carrier (IL-3 replaces the native binding domain of DT). When it binds to CD123, tagraxofusp is internalized and the catalytic domain of DT translocates to the cytoplasm, leading to inhibition of protein synthesis and cell death.

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 complete response with residual skin abnormality not indicative of active disease. The CR/CRc rate was 53.8% (7/13)  and the median duration of CR/CRc was not reached (range, 3.9-12.2 months).

Safety was assessed in 94 adults. The most common adverse reactions (incidence ≥ 30%) were capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase. The most common laboratory abnormalities (incidence ≥ 50%) were decreases in albumin, platelets, hemoglobin, calcium, sodium, and increases in glucose, alanine aminotransferase (ALT), and aspartate aminotransferase (AST).

Labeling also includes a boxed warning to alert healthcare professionals and patients about the increased risk of capillary leak syndrome, which may be life-threatening or fatal to patients receiving treatment.

The FDA has granted this application breakthrough therapy and priority review designation, and tagraxofusp also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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