WASHINGTON — The FDA announced new approvals for two rare and life-threatening blood diseases on Friday, as blastic plasmacytoid dendritic cell neoplasm (BPDCN) gets its first approved agent and paroxysmal nocturnal hemoglobinuria (PNH) gets a new drug that drastically cuts the frequency of treatments.
BPDCN Gets First Approved Drug
The FDA approved the infusion therapy tagraxofusp (Elzonris) for adults and children ages 2 years and up with BPDCN, a clinically aggressive disease that often presents as leukemia or evolves into an acute leukemia, and most commonly affects the skin, bone marrow, and lymph nodes.
“The standard of care has been intensive chemotherapy followed by bone marrow transplantation,” Richard Pazdur, MD, the FDA’s top hematology and oncology official, explained in a statement announcing the approval. “Many patients with BPDCN are unable to tolerate this intensive therapy, so there is an urgent need for alternative treatment options.”
Evidence for the approval of tagraxofusp came from a single-arm trial of 28 patients with BPDCN that included 13 who were untreated and 15 with relapsed or refractory disease. Among the untreated patients, 54% achieved a complete response (CR) or CR with a non–active disease skin abnormality. In the relapsed setting one patient achieved a CR and one achieved a CR with a non–active disease skin abnormality.
The drug comes with a host of side effects including the possibly deadly capillary leak syndrome (labeling carries a Boxed Warning for this side effect), nausea, peripheral edema, pyrexia, chills, weight gain, and others. Laboratory abnormalities observed in the clinical trial include albumin, calcium, hemoglobin, lymphocytes, and platelet decreases, as well as increases in aspartate transaminase (AST) and alanine aminotransferase (ALT). Liver enzyme levels should also be monitored for signs of infusion intolerance.
The agency warned that pregnant or breastfeeding women should not take tagraxofusp due to possible harms to the fetus or child.
The agency also announced the approval of ravulizumab (Ultomiris) for adults with PNH, a life-threatening acquired disorder that is usually diagnosed in young adults.
“The approval of Ultomiris will change the way that patients with PNH are treated,” Pazdur said. “Prior to this approval, the only approved therapy for PNH required treatment every two weeks, which can be burdensome for patients and their families. Ultomiris uses a novel formulation so patients only need treatment every eight weeks, without compromising efficacy.”
In patients with PNH, infections or physical exertion can lead to hemolysis, and when patients are having a PNH-related episode they can experience severe anemia, profound fatigue, shortness of breath, dark-colored urine, kidney disease, and recurrent pain.
The approval of ravulizumab was based on evidence from two randomized clinical trials, one in the untreated setting and another in patients with stable disease on eculizumab (Soliris), the current standard treatment.
In the treatment-naive trial of 246 PNH patients, ravulizumab was found to be non-inferior to eculizumab with regard to transfusion independence and incidence of hemolysis as measured by the normalization of lactate dehydrogenase (LDH) levels. The second trial of 195 patients with stable disease found ravulizumab to be non-inferior when patients switched drugs after being on eculizumab treatment for 6 months or more.
The two most common side effects of ravulizumab in these trials were headache and upper respiratory infection. The labeling for the drug includes a boxed warning due to the life-threatening risk of meningococcal infections and sepsis. Patients should be vaccinated for meningococcal at least 2 weeks prior to their first treatment. But the agency cautioned that vaccination only reduces the risk, so patients need to be carefully observed for early signs of meningococcal infections.