FDA approves hemoglobinuria drug from Alexion

Blood Disease Drug

On June 7 the FDA approved the ravulizumab-cwvz injection for treating children aged 1 month and older with paroxysmal nocturnal hemoglobinuria. Researchers evaluated the efficacy of ravulizumab-cwvz (Alexion’s Ultomiris) — previously approved for adults — among children in a 26-week study that enrolled 13 patients aged 9 to 17 years, eight of whom previously had received eculizumab Alexion’s Soliris.

Paroxysmal nocturnal hemoglobinuria is a rare, acquired, life-threatening blood disease that affects one to 1.5 people per million, with 10% of cases occurring among children. It occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. The disease is characterized by red blood cell destruction, by the complement system, a part of the body's innate immune system. It also causes anemia, blood clotting and impaired bone marrow function. Median survival is 10 years after diagnosis.

In the clinical trial patients received a first dose of ravulizumab-cwvz, followed by maintenance treatment 15 days later. Treatment continued every 8 weeks for patients weighing at least 44 pounds and every 4 weeks for those weighing less than 44 pounds.

The pharmacokinetic and pharmacodynamic effects of the treatment served as the study’s primary endpoints. Sixty percent of patients who had not previously received complement inhibitors did not need a blood transfusion, a secondary endpoint, through week 26. All patients who previously received eculizumab did not need a transfusion.

Ravulizumab-cwvz is only available through a risk evaluation and mitigation strategy due to the risk for meningococcal infections and other infections.

Last month the FDA approved pegcetacoplan for treatment of certain adults with paroxysmal nocturnal hemoglobinuria, according to the agent’s manufacturer, Apellis Pharmaceuticals. Pegcetacoplan (Empaveli), a targeted C3 inhibitor, is indicated for treatment-naive patients, as well as those switching from the C5 inhibitors eculizumab (Soliris, Alexion Pharmaceuticals) or ravulizumab (Ultomiris, Alexion Pharmaceuticals). The FDA based the approval on results of the phase 3 PEGASUS study, which showed pegcetacoplan led to greater improvements in hemoglobin compared with eculizumab among patients with paroxysmal nocturnal hemoglobinuria (PNH).

“Empaveli has the potential to improve the lives of patients with PNH by increasing hemoglobin and reducing blood transfusion requirements,” investigator Olga Frankfurt, MD, associate professor in the department of medicine at Robert H. Lurie Comprehensive Cancer Center at Northwestern University, said in an Apellis-issued press release. “Through my work as an investigator on the PEGASUS study, I was excited to see Empaveli providing broad control of PNH.”

The PEGASUS study included 80 patients enrolled across 44 centers who had hemoglobin levels of less than 10.5 g/dL while they received stable doses of eculizumab for at least 3 months.

The trial treatment consisted of three parts:

In a 4-week run-in phase, all patients continued their current dose of eculizumab with an addition of twice-weekly 1,080 mg subcutaneous pegcetacoplan;

In a 1:1 randomization phase, patients received monotherapy with pegcetacoplan or eculizumab for 16 weeks; and

In a 32-week period, all patients received open-label pegcetacoplan.

In the randomization phase, researchers randomly assigned 41 patients (mean age, 50.2 years; 66% women) to pegcetacoplan and 39 patients (mean age, 47.3 years; 56% women) to eculizumab. Changes in hemoglobin level from baseline to week 16 served as the study’s primary endpoint.

As Healio previously reported, results showed the adjusted mean change in hemoglobin from baseline to week 16 was 2.37 g/dL with pegcetacoplan compared with –1.47 g/dL with eculizumab, for a mean difference of 3.84 g/dL (95% CI, 2.33-5.34).

Thirty-five patients (85.3%) assigned pegcetacoplan no longer required transfusions, compared with six patients (14.6%) assigned eculizumab (P < .001).

“As the first, FDA-approved targeted C3 therapy, Empaveli has the potential to redefine treatment for adults with PNH, including patients switching from any C5 inhibitor and treatment-naive patients,” Cedric Francois, MD, PhD, co-founder and CEO of Apellis, said in the release.

The most common serious adverse event reported among pegcetacoplan-treated patients was infection (5%). The most common adverse events included injection site reactions (39%), infections (29%), diarrhea (22%), abdominal pain (20%), respiratory tract infection (15%), viral infection (12%), and fatigue (12%). Researchers reported no cases of meningitis and no deaths in the pegcetacoplan group.

The prescribing information for pegcetacoplan includes a boxed warning noting the agent may increase the risk for meningococcal or other serious infections caused by encapsulated bacteria. These infections may be fatal if not recognized or treated early.

The FDA approved a Risk Evaluation and Mitigation Strategy (REMS). Prescribers must counsel patients about the risk for serious infection, provide patients with the REMS educational materials, and ensure patients are vaccinated against encapsulated bacteria, according to the press release.