The FDA Approves Two Orphan Blood Disorder Drugs

The U.S.Food and Drug Administration (FDA) approved two drugs for separate blood disorders, Alexion Pharmaceuticals’ Ultomiris for the rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH), and Stemline Therapeutics’ Elzonris for blastic plasmacytoid dendritic cell neoplasm (BPDCN).

For Alexion, the FDA approval was two months ahead of its February PDUFA date, although share prices of company stock do not reflect the good news, as they have been caught up in the overall market negativity stemming from the government shutdown and other factors. Ultomiris, a long-acting C5 complement inhibitor, is considered the successor to the company’s blockbuster PNH drug Soliris.

PNH is a rare blood disease where the red blood cells are destroyed by a part of the body’s immune system known as the complement system.

Ultomiris is an improved version of Soliris. Trial results show that patients could safely be dosed once every eight weeks with Ultomiris (formerly known as ALXN1210) compared to every two weeks with Soliris – a key point that the FDA honed in on for approval. Richard Pazdur, head of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products, said the greater length of time between doses for patients on Ultomiris will benefit the quality of life in patients. Dosing every two weeks can be burdensome for patients and their families, he said.

“Ultomiris uses a novel formulation so patients only need treatment every eight weeks, without compromising efficacy,” Pazdur said in a statement.

During clinical trials, Ultomiris showed non-inferiority against Soliris in patients with PNH who had been stable on Soliris based on the primary endpoint of change in lactate dehydrogenase (LDH) levels. Those levels are a direct marker of complement-mediated hemolysis in PNH.

John Orloff, head of research and development at Alexion, said the company is proud that it was able to bring Ultomiris to PNH patients less than three years after it first reported positive Phase III data.

“Immediate and complete C5 inhibition with Ultomiris, sustained for eight weeks, can provide meaningful benefits for patients and their families. Based on the totality of our compelling data from the largest Phase 3 program ever conducted in PNH, we believe Ultomiris has the potential to become the new standard of care for patients with PNH,” Orloff said in a statement.

Also snagging approval for a blood disorder was Stemline Therapeutics. The FDA approved Elzonris, the first ever-approved treatment for blastic plasmacytoid dendritic cell neoplasm. Additionally, Stemline noted that Elzonris is also the first approved CD123-targeted therapy.

BPDCN is an aggressive, orphan blood disorder with historically poor outcomes. Stemline said that BPDCN can often present symptoms that can be mistaken for blood cancers, such as acute myeloid leukemia and non-Hodgkin’s lymphoma. BPDCN typically presents in the bone marrow and/or skin, and may also involve lymph nodes and viscera. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, the company said.

CD123 is a key marker in identifying BPDCN and is a rapidly emerging target for therapeutic research in a variety of cancers. Elzonris is designed to specifically target CD123, and, within a triad of signature markers, enables proper diagnosis.

Naveen Pemmaraju, an associate professor at The University of Texas MD Anderson Cancer Center, and a principal investigator for Elzonris, said the approval of the drug marks a major step forward for patients with BPDCN. He said the approval provides a new standard-of-care for patients.  

The FDA’s Pazdur said that prior to the approval of Elzonris, the standard of care for BPDCN patients has been intensive chemotherapy followed by bone marrow transplantation. He said that many patients are unable to tolerate such an intensive form of therapy, which has created a critical need for alternative treatments.

Both Stemline’s Elzonris and Alexion’s Ultomiris were granted Breakthrough Therapy designation, as well as Orphan Drug designation.