FDA approval for Stemline Therapeutics Inc.'s Elzonris (tagraxofusp) has made it the first drug ever approved for blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and aggressive disease of the bone marrow and blood. The green light, which covers both adult and pediatric patients ages 2 and older, arrived two months ahead of the date by which the regulator was expected to release its decision.

Elzonris, which has secured orphan status in both the U.S. and Europe, was granted an FDA breakthrough designation in August 2016 and priority review in August. It was also selected by the EMA in November for accelerated assessment in BPDCN, suggesting an approval in the EU may not be far behind. Stemline said that it will be commercially available for appropriate people with BPDCN in early 2019.

Pricing information has not yet been disclosed, but an early consensus estimate has projected that sales of the medicine might reach $34 million in 2019, more than doubling to $84 million in 2020. However, individual treatment needs and durations will vary, the company said, a factor which could undermine the reliability of such estimates.

The standard of care for BPDCN so far has been intensive chemotherapy followed by bone marrow transplant. But many patients with the disease are unable to tolerate that, "so there is an urgent need for alternative treatment options," said Richard Pazdur, director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.

A biological conjugate, Elzonris consists of human IL-3 linked to a truncated diphtheria toxin that targets ILR-3-alpha (CD123) on cancer stem cells. Its efficacy was studied in two cohorts of patients in a single-arm trial. In the first cohort, which enrolled 13 patients with untreated BPDCN, seven achieved complete remission (CR) or CR with a skin abnormality not indicative of active disease (CRc). In the second cohort, which included 15 patients with relapsed or refractory BPDCN, one patient achieved CR and one patient achieved CRc. Designed with input from the FDA, it was the largest multicenter prospective study conducted in the indication, according to Stemline. (See BioWorld, Nov. 1, 2017.)

Elzonris was approved with a black-boxed warning regarding an increased risk of potentially life-threatening capillary leak syndrome, a side effect in which fluid and proteins leaking out of tiny blood vessels into surrounding tissues. Other common side effects reported by patients in trials of the drug included nausea, fatigue, swelling of legs and hands, fever, chills and weight increase.

The most common laboratory abnormalities were decreases in lymphocytes, albumin, platelets, hemoglobin and calcium, and increases in glucose and liver enzymes.

BPDCN is very rare, and accounts for just 0.44 percent of all hematologic malignancies and 0.7 percent of cutaneous lymphomas, according to epidemiological data compiled by Cortellis. Stemline estimates that it may affect as many as 500 people annually in the U.S., but reliable figures are hard to come by because it is often underdiagnosed, misdiagnosed and under-reported. That has led Stemline to invest in actively helping raise awareness of it.

BPDCN may present with features similar to, and can be mistaken for, certain diseases including acute myeloid leukemia, non-Hodgkin lymphoma, acute lymphocytic leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia (CMML), as well as other malignancies with skin manifestations, the company said.

Elzonris is also being evaluated in additional clinical trials in other indications including CMML, myelofibrosis and other CD123 positive diseases.

Meanwhile, additional candidates from Stemline's competitors are under investigation as potential therapies for BPDCN. They include Immunogen Inc.'s CD123-targeted IMGN-632; the bispecific XmAb-14045, a Xencor Inc. drug licensed by Novartis AG that targets CD3 and CD123; and the Cellectis SA-originated anti-CD123 T-cell therapy UCART-123, which MD Anderson Cancer Center is developing for potential treatment of BPDCN.

Shares of Stemline (NASDAQ:STML) fell 45 cents, or 5.2 percent, to close at $8.23 on Friday.

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