Novartis received approval from the U.S. Food and Drug Administration (FDA) on Dec. 5, 2023, for Fabhalta^® (iptacopan) capsules. It blocks a new complement pathway to treat adults who have paroxysmal nocturnal hemoglobinuria (PNH). As the first drug that specifically targets Factor B, Fabhalta is different from complement 3 or 5 (C3 or C5) inhibitors to prevent the breakdown (hemolysis) of red blood cells (RBCs) both within blood vessels (intravascular) and in the liver, lymph nodes and spleen (extravascular). The recommended dose is 200mg twice each day. Fabhalta has a boxed warning and a risk evaluation and mitigation strategy (REMS) due to the risk of severe infections that may be associated with its use. The launch is expected before the end of the year, but cost is not yet available. Here is the full prescribing information.

At a Glance

• Brand (Generic) Name: Fabhalta (iptacopan)
• Manufacturer: Novartis

1. Date Approved: Dec. 5, 2023
2. Indication: monotherapy for treating adults who have PNH
3. Dosage Forms Available: 200mg oral capsules
4. Launch Date: December 2023

• Estimated Annual Cost: Pricing information is not yet available.
• A rare blood disorder, PNH is caused by spontaneous mutations of a protein that attracts and holds other proteins, including some that protect against the complement parts of the immune system, onto the surfaces of RBCs.
• As a result, bone marrow produces fewer and more fragile than normal blood cells of all types. The RBCs of patients who have PNH are easily destroyed by immune proteins called complement. 
• Up to one-half of patients who receive the current standard therapy for PNH with a C3 or C5 inhibitor still need blood transfusions and a large percentage have persistent anemia because currently available complement inhibitors are not very effective for extravascular hemolysis.
• Hemoglobin (Hgb) levels, which normally range from 14 to 18gm/dL for men and 12 to 16gm/dL for women, typically are decreased by PNH. 
• Increased levels of an enzyme, lactate dehydrogenase (LDH), serve as biomarkers for intravascular hemolysis.
• PNH is believed to affect between 0.5 and 1.5 people per one million in the general population — fewer than 500 patients in the United States.
• By interrupting Factor B, part of the alternative complement cascade, Fabhalta acts differently from other complement inhibitors to manage PNH.
• In one phase III clinical trial that included patients who had received prior treatment for PNH, none of the patients taking Fabhalta needed blood transfusions. Additionally, Hgb levels increased by 2gm/dL or more after 24 weeks for 82.3% of patients taking Fabhalta as compared to none of the patients who continued their current treatments.
• In a separate phase III study of patients who had not been previously treated for PNH, only 2.4% of those taking Fabhalta needed a blood transfusion at the 24-week point in the trial. LDH levels fell by an average of 83.6%, as well.
• Because disrupting the complement system may affect immune function, Fabhalta has a boxed warning and a REMS to alert prescribers and patients about the potential for life-threatening infections that may be caused by taking it.
• The most common side effects reported by study participants taking Fabhalta include headache, diarrhea, abdominal pain, nausea, and infections.
• No other Factor B inhibitors are FDA-approved.
• Soliris^® (eculizumab), FDA approved in 2007, and Ultomiris^® (ravulizumab-cwvz), in 2018; are C5 inhibitors that are injected intravenously (IV). After five weekly doses, Soliris is injected once every two weeks. Ultomiris is given once every eight weeks following a single loading dose two weeks before the maintenance regimen begins. Ultomiris is also supplied as a subcutaneous on-body injector. They work only for intravascular hemolysis.
• In 2021, a C3 inhibitor, Empaveli^® (pegcetacoplan) was approved by the FDA. It is infused subcutaneously twice a week to manage both intravascular and extravascular hemolysis.
• Previously given Orphan Drug status for treating PNH and other conditions, Fabhalta was approved as a Breakthrough Therapy.