FDA Action Alert: Alexion, Stemline Therapeutics and Incyte

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While the U.S. Food and Drug Administration (FDA) digs through its backlog after the 35-day federal government shutdown, there’s some evidence that, in terms of priority review, the agency was ahead of the game. Two of the three drugs that were up for review in mid- to late-February received much earlier approval on December 21, the day before the federal government shutdown. The shutdown ended on January 25, 2019.

Here’s a look.

Alexion Pharmaceuticals’ ALXN1210 for Paroxysmal Nocturnal Hemoglobinuria

Alexion Pharmaceuticals had a target action date of February 18 for its Biologics License Application (BLA) for ALXN1210, its long-acting C5 complement inhibitor for paroxysmal nocturnal hemoglobinuria (PNH). Surprisingly, the FDA approved the drug much further ahead of that date, on December 21, 2018. It was being evaluated as part of an expedited eight-month review instead of the 12-month review because of Alexion’s rare disease priority review voucher.

Now named Ultomiris (ravulizumab-cwvz), the drug also is under review in the European Union and Japan.

PNH is a chronic, progressive, debilitating, and possibly life-threatening ultra-rare blood disease. The average age of onset is the early 30s. It is under-diagnosed, with diagnostic delays ranging from one to 10 years. The disease results when a component of the body’s immune system, the complement system, attacks red blood cells, which causes anemia, fatigue, dark urine, and shortness of breath. Chronic hemolysis can cause blood clots, which can damage vital organs and cause premature death.

“Ultomiris is a compelling new therapy for patients with PNH,” stated Ilene Weitz, associate professor at the Keck School of Medicine at the University of Southern California in Los Angeles, at the time of the approval. “I am particularly pleased by the positive data in patients transitioning from Soliris to Ultomiris without interruption, which is critical when you treat a devastating disease like PNH. This gives me confidence in recommending that patients switch therapy.”

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Stemline Therapeutics Elzonris for Blastic Plasmacytoid Dendritic Cell Neoplasm

Stemline Therapeutics, based in New York, had a target action date of February 21 for its BLA for Elzonris (tagraxofusp, SL-401) for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). This was under Priority Review. The drug also received Orphan Drug Designation. The FDA, again jumping ahead, approved the BLA on December 21, 2018.

The drug is a targeted investigational therapy directed to CD123, a cell surface receptor expressed on several cancers. On January 30, 2019, the European Medicines Agency (EMA) also completed its validation of the company’s Marketing Authorization Application (MAA) for Elzonris.

Elzonris is the first treatment approved for BPDCN and the first approved CD123-targeted therapy.

BPDCN is an aggressive, orphan hematologic cancer with poor outcomes. It can present with symptoms similar to and can sometimes be mistaken for diseases like acute myeloid leukemia, non-Hodgkin’s lymphoma, acute lymphocytic leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia, as well as other cancers with skin manifestations. It typically presents in the bone marrow and/or skin.

“Today’s approval of tagraxofusp is a major step forward for people with BPDCN, their families and the medical community,” stated Naveen Pemmaraju, associate professor at The University of Texas MD Anderson Cancer Center, and a principal investigator on the tagraxofusp clinical trial. “CD123 is expressed in BPDCN and a number of other hematologic malignancies. The approval of tagraxofusp, a CD123-targeted therapy, represents a new standard of care for patients with BPDCN.”

Incyte’s Jakafi (Ruxolitinib) for Steroid-Refractory Acute GVHD

Incyte Corporation has a target action date of February 24 for its supplemental New Drug Application (sNDA) for ruxolitinib for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). This was accepted for Priority Review.

On December 3, 2018, Incyte updated data from its pivotal Phase II REACH1 trial of Jakafi in combination with corticosteroids to treat acute GVHD who have an inadequate response to corticosteroids. The study met its primary endpoint, showing an overall response rate (ORR) of 55 percent at Day 28, along with a best overall response rate (BORR) of 73 percent.

GVHD is a condition that can occur after an allogeneic transplant. In it, the donated bone marrow or peripheral blood stem cells treat the recipient’s body as foreign and attack it, leading to significant morbidity and mortality. There are two types, acute and chronic. Acute GVHD typically happens within the first 100 days after a transplant. In acute GVHD, up to 40 percent have severe disease, resulting in a 12-month survival of 50 percent or less.

However, on Feb. 7, 2019, the company announced that the FDA had extended its target action date to May 24, 2019. This is to allow time for the agency to review additional data the company submitted in response to FDA requests. The submissions were such that they constituted a Major Amendment to the sNDA, causing the extension by three months.

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