FDA Grants Priority Review to sBLA of Ultomiris for Treatment of aHUS

The U.S. Food and Drug Administration (FDA) has granted Priority Review to the supplemental Biologics License Application (sBLA) for Alexion‘s Ultomiris (ravulizumab-cwvz) for the treatment of patients with atypical hemolytic uremic syndrome (aHUS).

aHUS is caused by the progressive destruction of red blood cells due to the dysregulation of the complement system — a set of more than 20 blood proteins that form part of the body’s immune defenses. Damaged red blood cells can aggregate and form clots that clog the kidney’s small blood vessels (thrombotic microangiopathy, or TMA), potentially leading to kidney failure.

Ultomiris is a monoclonal antibody that has been designed to bind and inhibit the activity of the C5 protein, preventing overactivation of the complement system and the destruction of red blood cells associated with aHUS.

According to Alexion, Ultomiris is the first and only long-acting C5 inhibitor currently in the market that provides immediate and sustained inhibition of the complement system up to eight weeks after its administration.

In December 2018, the FDA approved Ultomiris for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH), a serious blood disorder also caused by a dysregulation of the complement system.

The sBLA submitted by Alexion to the FDA was largely based on data from the company’s global, multi-center, single-arm, Phase 3 trial (NCT02949128) assessing the safety and efficacy of intravenous Ultomiris in 56 adult patients with aHUS.

Data from the trial were recently announced at a presentation titled, “Efficacy and safety of the long-acting complement C5 inhibitor ravulizumab in adult patients with atypical hemolytic uremic syndrome (aHUS),” at the Annual Congress of the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA), June 13-16 in Budapest, Hungary.

The trial’s primary endpoint was complete TMA response, defined by a normalization in the number of platelets and in the levels of lactate dehydrogenase (LDH, an enzyme whose levels can be used as a readout of red blood cells’ destruction), as well as a minimum of 25% improvement in kidney function (assessed by levels of serum creatinine).

The study met its primary endpoint, with about 54% of patients reaching a complete TMA response.

Moreover, 83.9% of the patients achieved a normal platelet count, 76.8% a normalization in the levels of LDH, and 58.9% a significant improvement in kidney function after treatment with Ultomiris.

“This acceptance is an important step in our efforts to deliver a potential new standard of care to people living with this devastating disease,” John Orloff, MD, executive vice president and head of research & development at Alexion, said in a press release. “We look forward to working closely with the FDA to facilitate a rapid review of this application.”

The FDA has signed a Prescription Drug User Fee Act (PDUFA), which allows the federal agency to collect fees from drug manufacturers to expedite the drug approval process, with a target date of Oct. 19. By then, the FDA must come to a decision on whether Ultomiris should be approved for this indication.