FDA Grants Elzonris a Priority Review to Treat a Rare Blood Cancer

The FDA has granted a priority review designation to a biologics license application (BLA) for SL-401 (tagraxofusp, Elzonris) for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to Stemline Therapeutics, the developer of the novel stemness inhibitor.

The drug is directed at the IL-3 receptor, which is overexpressed on cancer stem cells and/or tumor bulk in many hematologic malignancies. Elzonris is being investigated as a first-line or later treatment in patients with BPDCN in a phase 1/2 trial (NCT02113982).

Positive findings from the trial were presented at the 2017 ASH Annual Meeting, where Elzonris demonstrated strong activity in patients with BPDCN. Across three stages of the trial, 42 patients received Elzonris at a dose of 12 μg/kg each day. In first-line BPDCN, the overall response rate (ORR) was 90 percent (26 out of 29 evaluable patients), with a complete response (CR) rate of 72 percent (21 of 29).

After therapy with Elzonris, 45 percent of patients (13 of 29) were bridged to stem cell transplant (SCT). In patients with relapsed/refractory BPDCN, the ORR was 69 percent (9 of 13), with a 38 percent CR rate (5 of 13), and one patient was bridged to SCT.

The median overall survival was not reached in patients who received Elzonris therapy in the first-line setting. In the pivotal stage 3 cohort, the study met its primary endpoint with a 54 percent CR rate (7 of 13). The ORR was 77 percent and 46 percent of patients were bridged to SCT (6 of 13). The most common treatment-related adverse events (AEs) were alanine aminotransferase increase (52 percent), aspartate aminotransferase increase (50 percent), hypoalbuminemia (50 percent), and thrombocytopenia (38 percent). Capillary leak syndrome was also noted in 19 percent of patients, which was grade 5 in 1 patient.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make a decision on the BLA by Feb. 21, 2019.

“The acceptance of our BLA for filing and grant of priority review represent tremendous milestones for Stemline and the BPDCN patient community. We would like to thank the patients and their families who participated in our clinical trials, as well as recognize the tireless work of our investigators and entire Stemline team. Given both priority and breakthrough status, our commercial organization is positioning itself to rapidly launch Elzonris, if approved, to ensure this important new treatment reaches patients as quickly as possible,” Ivan Bergstein, M.D., Stemline’s CEO, said in a statement.

The most significant adverse event (AE) associated with Elzonris is the risk of capillary leak syndrome. During the phase 1/2 study, all patients are being closely monitored for signs of capillary leak. Other AEs associated with the drug are mostly grade 1/2 in severity, and include hypoalbuminemia, increases in aspartate and alanine aminotransferase, and thrombocytopenia.

BPDCN affects mostly elderly patients, who may not be able to tolerate chemotherapies. Elzonris may have a better safety and toxicity profile for this patient population due to its targeted mechanism of action. The drug is an IL-3 conjugated truncated diphtheria toxin, which essentially delivers diphtheria toxin to cells that have the IL-3 receptor. Many hematologic malignancies have CD123 expression, but BPDCN in particular has characteristically high expression. When the diphtheria toxin penetrates a cell, it binds to and ADP-ribosylates elongation factor 2, a factor necessary for protein translation. When the protein synthesis process is inhibited, the cell dies by apoptosis.

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