FDA endorses Novartis' 'pipeline in a pill,' granting first nod for potential blockbuster Fabhalta

Novartis has gained the first of what it hopes are several FDA approvals for its factor B inhibitor iptacopan, dubbed two months ago “a pipeline in pill,” by analysts at ODDO BHF.

The United States regulator has given a thumbs up to iptacopan to treat paroxysmal nocturnal hemoglobinuria (PNH). Known commercially as Fabhalta, it becomes the first oral monotherapy approved by the FDA for the rare blood disorder, which affects 10 to 20 people per one million worldwide.

Novartis has big ambitions for iptacopan and is lining it up to address other complement-mediated renal and hematological diseases, including primary immunoglobulin A nephropathy (IgAN), also known as Berger’s disease. Analysts at Jefferies have pegged iptacopan’s peak sales potential at $3.6 billion.

Fabhalta acts in the alternate complement pathway of the immune system, providing control of red blood cell destruction. Those with PNH have a mutation that causes them to produce red blood cells susceptible to premature destruction, which can cause anemia, bone marrow failure, thrombosis and other symptoms.

The approval in PNH covers adults who have and have not been previously treated. C5 inhibitors, such as AstraZeneca’s blockbusters Soliris and Ultomiris, are the most common treatment. Because Fabhalta acts upstream of the C5 terminal pathway, it may have an advantage in preventing blood cell destruction. Another edge is Fabhalta’s oral administration, versus injection or infusion for the C5s.

The FDA approval was backed by phase 3 trials that showed Fabhalta increased hemoglobin levels in both previously treated and treatment naïve patients.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing,” Vinod Pullarkat, M.D., of the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, said in a 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.”

Novartis said Fabhata will be available later this month but did not reveal its price. The treatment will carry a boxed warning for increased risk of “life-threatening infections caused by encapsulated bacteria.” It will be made available through a Risk Evaluation and Mitigation Strategy (REMS) program that requires vaccinations for encapsulated bacteria.

Next up for iptacopan is an FDA application in IgAN for a potential fast-track approval in 2024. Data released in October from the phase 3 APPLAUSE-IgAN study showed that iptacopan hit its pre-specified interim endpoint with significant proteinuria reductions. The results prompted analysts at ODDO BHF to laud the performance as “faultless.”  

Novartis also is evaluating iptacopan in a phase 3 study in C3 glomerulopathy. The drugmaker is further testing the drug in atypical hemolytic uremic syndrome (aHUS) and immune complex membranoproliferative glomerulonephritis (IC-MPGN).