FDA approves Novartis’ Fabhalta, a groundbreaking oral monotherapy for rare blood disease treatment

SWITZERLAND — The U.S. Food and Drug Administration (FDA) has approved Novartis’ oral drug iptacopan, branded as Fabhalta, marking a significant milestone in the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

Fabhalta becomes the first oral monotherapy endorsed by the FDA to address this rare blood disorder, impacting 10 to 20 individuals per one million globally.

PNH is characterized by red blood cell susceptibility to premature destruction due to a genetic mutation, leading to anemia, bone marrow failure, thrombosis, and other complications.

Fabhalta, a Factor B inhibitor, operates in the alternate complement pathway of the immune system, offering control over red blood cell destruction.

Novartis envisions Fabhalta as not only a breakthrough for PNH treatment but also a potential solution for complement-mediated renal and hematological diseases, including primary immunoglobulin A nephropathy (IgAN or Berger’s disease).

Analysts project Fabhalta’s peak sales potential at an impressive US$3.6 billion. Anti-C5 drugs like Soliris and Ultomiris are currently standard treatments for PNH.

Unlike the conventional C5 inhibitors, such as Soliris and Ultomiris, Fabhalta’s distinct advantage lies in acting upstream of the C5 terminal pathway.

This positioning may enhance its efficacy in preventing blood cell destruction. Additionally, its oral administration provides a practical alternative to the injection or infusion required for the C5 inhibitors.

FDA approval for Fabhalta covers both previously treated and treatment-naïve adults. Phase 3 trials supported the approval, demonstrating increased hemoglobin levels in patients across both groups.

Vinod Pullarkat, M.D., from the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, emphasized the potential practice-changing impact of an efficacious oral treatment.

Fabhalta is expected to be available later this month, with Novartis yet to disclose its pricing. The treatment comes with a boxed warning about an increased risk of life-threatening infections caused by encapsulated bacteria.

A Risk Evaluation and Mitigation Strategy (REMS) program, mandating vaccinations for encapsulated bacteria, will be implemented.

Looking ahead, Novartis has initiated an FDA application for IgAN, with potential fast-track approval anticipated in 2024.

Promising results from the phase 3 APPLAUSE-IgAN study in October highlighted significant proteinuria reductions.

Novartis is also exploring Fabhalta’s applications in C3 glomerulopathy, atypical hemolytic uremic syndrome (aHUS), and immune complex membranoproliferative glomerulonephritis (IC-MPGN).

Common side effects include headache, nasopharyngitis, diarrhea, abdominal pain, and infections.

Novartis aims to challenge the market dominance of anti-C5 drugs and increase treatment rates for the substantial number of untreated PNH patients in the U.S.

Their success on the market was a large part of why AstraZeneca paid US$39 billion to acquire their developer, Alexion Pharmaceuticals, in December 2020.

Novartis estimates approximately 6,000 PNH patients in the U.S., targeting not only those currently on complement inhibitors but also the 70% not receiving any therapy.

Novartis plans to make Fabhalta commercially available in December, with ongoing regulatory reviews in other countries.

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