FDA approves Ultomiris for rare blood disease

Alexion receives early FDA approval for Ultomiris (ravulizumab) in adults with paroxysmal nocturnal hemoglobinuria (PNH)

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BOSTON—Alexion Pharmaceuticals, Inc. has announced that the U.S. Food and Drug Administration (FDA) approved Ultomiris (ravulizumab) injection for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH), a debilitating, rare and life-threatening blood disorder characterized by complement-mediated destruction of the red blood cells (hemolysis).
The approval of Ultomiris comes ahead of the Prescription Drug User Fee Act date of February 18, 2019, set by the FDA as part of an expedited eight month review following Alexion’s use of a rare disease priority review voucher.
John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion said, “We are proud to bring Ultomiris to patients suffering from this devastating disease less than a year after reporting our positive Phase 3 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.”
Ultomiris is reportedly the first and only long-acting C5 inhibitor. It works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system that, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders like PNH, atypical hemolytic uremic syndrome, and anti-acetylcholine receptor antibody-positive myasthenia gravis.
“We applaud the FDA’s approval of Ultomiris. It is important news for patients with PNH and their families. The introduction of Soliris (eculizumab) eleven years ago transformed the lives of patients with PNH,” noted Neil Horikoshi, Chief Executive Officer of the Aplastic Anemia and Myelodysplastic Syndrome (AAMDS) International Foundation. “But the management of this debilitating disease still requires strength and sacrifice from patients and their families. With Ultomiris, patients no longer have to plan their lives around bi-weekly infusions and can look forward to just six or seven infusions a year.”
PNH is an acquired disorder. Patients with PNH are missing a certain protein that normally protects red blood cells from being destroyed by the patient’s immune system. PNH causes sudden, recurring episodes where red blood cells are prematurely destroyed. These may be triggered by stresses on the body, such as infections or physical exertion.
Symptoms during these episodes can include severe anemia, profound fatigue, shortness of breath, intermittent episodes of dark colored urine, kidney disease and recurrent pain. The most devastating consequence of chronic hemolysis is thrombosis, which can occur in blood vessels throughout the body, damage vital organs and cause premature death. PNH can occur at any age, although it is most often diagnosed in young adulthood. Despite historical supportive care, including transfusion and anticoagulation management, 20 to 35 percent of patients with PNH die within five to 10 years of diagnosis.
“The approval of Ultomiris will change the way that patients with PNH are treated,” added Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Ultomiris uses a novel formulation so patients only need treatment every eight weeks, without compromising efficacy.”
The efficacy of Ultomiris was studied in a clinical trial of 246 treatment naïve patients, who were randomized to be treated with Ultomiris or eculizumab, the current standard of care for PNH. The results of the trial demonstrated that Ultomiris had similar results to eculizumab (non-inferior) – patients did not receive a transfusion and had similar incidence of hemolysis measured by the normalization of LDH levels in patients’ blood (lactate dehydrogenase, or LDH, is an enzyme required during the process of turning sugar into energy in the body’s cells).
In addition, Ultomiris was studied in a second clinical trial of 195 patients with PNH who were clinically stable after having been treated with eculizumab for at least the past six months. These patients were randomly selected to be treated with Ultomiris or to continue eculizumab. Ultomiris again demonstrated similar effects to eculizumab (non-inferior) based on several clinical measures including hemolysis and avoiding transfusion.
The comprehensive results from the two Phase 3 studies were recently published in Blood. The safety profile of Ultomiris was similar to that of Soliris. Recently presented additional data showed that Ultomiris provided immediate and complete C5 inhibition that was sustained for eight weeks, and that Ultomiris eliminated breakthrough hemolysis associated with incomplete C5 inhibition. The entire clinical development program for Ultomiris to date represents more than 600 patient years of experience.
“Ultomiris is a compelling new therapy for patients with PNH. It has met the high bar for efficacy and safety established by Soliris and has a four times longer dosing interval. 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,” mentioned Ilene Weitz, M.D., Associate Professor at the Keck School of Medicine at the University of Southern California in Los Angeles. “This gives me confidence in recommending that patients switch therapy.”
The FDA granted this application Priority Review designation. Ultomiris also received Orphan Drug designation. As well, regulatory authorities in the European Union and Japan have accepted and are reviewing applications for the approval of Ultomiris as a treatment for adults with PNH.

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