FDA Approves Fabhalta, an Oral Treatment for Rare Blood Disorder

The FDA has approved Novartis’ Fabhalta (iptacopan) as the first oral monotherapy to treat adults with paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare, acquired blood disorder that can destroy the complement system, a part of the body’s immune system. This can lead to the destruction of red blood cells within blood vessels, spleen and liver, as well as blood clots and anemia. About 10 to 20 people per million worldwide live with PNH. It is often diagnosed in people between 30 and 40 years of age.

Therapies exist to treat patients with PNH — including Soliris (eculizumab), Ultomiris (ravulizumab) and Empaveli (pegcetoplan) — but they are administered by IV infusion. Soliris and Ultomiris work to block complement protein C5. Empaveli inhibits the C3 protein. Despite treatment with anti-C5s, a large proportion of people with PNH may remain anemic, and dependent on blood transfusions. The only cure is a bone marrow transplant.

Fabhalta is an oral treatment that can help control red blood cell destruction within and outside the blood vessels. It is a Factor B inhibitor that acts in the alternative complement pathway of the immune system. Fabhalta will be available later this month and have a wholesale acquisition cost of $550,000 per year.

A Novartis spokesperson said the company is committed to providing patients with access and resources, including the Novartis Patient Support. The program also includes dedicated assistance and educational resources to help patients get started on treatment.

Vinod Pullarkat, M.D.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, M.D., clinical professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, said in a press release. “In clinical studies, iptacopan was superior to anti-C5s in hemoglobin improvement in the absence of RBC transfusion and transfusion avoidance rate, and also effective in complement inhibitor-naïve individuals, by providing clinically meaningful hemoglobin-level increases without the need for blood transfusions.”

The FDA approval is based on the phase 3 APPLY-PNH trial in 97 patients with residual anemia despite prior anti-C5 treatment who switched to Fabhalta, which demonstrated hemoglobin improvement with red blood cell. It also improved patients’ ability to avoids transfusions compared with patients who stayed on anti-C5 treatments.

In the APPLY-PNH trial, the most commonly reported adverse reactions with Fabhalta vs. anti-C5s were: headache, nasopharyngitis, diarrhea, abdominal pain, bacterial infection, nausea and viral infection. In the APPOINT-PNH trial, the most commonly reported adverse events were headache, viral infection, nasopharyngitis, and rash.

In APPLY-PNH, serious ARs were reported in two (3%) patients with PNH receiving Fabhalta, which included pyelonephritis, urinary tract infection and COVID-19. In APPOINT-PNH, serious ARs were reported in two (5%) patients with PNH receiving Fabhalta, which included COVID-19 and bacterial pneumonia.

Approval was also supported by the phase 3 APPOINT-PNH study in 40 patients who were complement inhibitor-naïve.

Fabhalta is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria.

Fabhalta is also in development for a range of complement-mediated diseases, including immunoglobulin A nephropathy, C3 glomerulopathy, immune complex membranoproliferative glomerulonephritis (IC-MPGN) and atypical hemolytic uremic syndrome.