Novartis gets FDA green light for first of three IgAN therapies

Novartis has requested accelerated FDA approval for a second indication for Fabhalta – IgA nephropathy (IgAN) – as it prepares to deliver blockbuster sales for the drug.

The U.S. regulator has approved Fabhalta (iptacopan) for the reduction of proteinuria in adults with primary IgAN who are at risk of rapid disease progression, making it the first complement inhibitor for this rare kidney disease.

Fabhalta is already approved in the US, EU and Japan as a treatment for paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder, and is the first oral alternative to complementary injectable or infused therapies such as AstraZeneca’s Soliris (eculizumab) and Ultomiris (ravulizumab) and Apellis’s Empaveli (pegcetacoplan), which are not used to treat IgAN.

The approval of IgAN is based on data from the ongoing APPLAUSE-IgAN study which showed a 38% reduction in proteinuria at nine months with the drug compared to placebo.

Proteinuria is a marker of kidney function, and therefore a surrogate marker of drug activity in IgAN, which occurs when antibodies build up in the kidneys, causing inflammation and scarring and potentially leading to chronic kidney disease (CKD).

According to Novartis, despite standard care, up to 50% of IgAN patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis. Each year, approximately 25 out of every million people worldwide are newly diagnosed with IgAN, primarily young adults.

The green light is also a milestone for Novartis, as it marks the first approval in its kidney disease pipeline, which includes three IgAN therapies: Fabhalta, the oral endothelin A receptor antagonist atrasentan, and zigakibart, a subcutaneous anti-APRIL antibody. Atrasentan was filed with the FDA earlier this year, while zigakibart is in Phase 3.

In 2021, Calliditas Therapeutics’ corticosteroid drug Tarpeyo (budesonide) became the first FDA-approved treatment for IgAN, and last year it was joined by Travere Therapeutics’ Filspari (sparsentan), which is in the same class as atrasentan. Previously, the standard of care consisted of broad-spectrum immunosuppressive drugs, with potentially serious side effects.

“The heterogeneous and progressive nature of IgA nephropathy has made effective treatment of this disease challenging. Fortunately, the therapeutic landscape is rapidly evolving,” commented Professor Dana Rizk of the University of Alabama, APPLAUSE-IgAN investigator.

“A growing body of clinical evidence highlights the critical role of complement activation in IgA nephropathy,” she added. “I am pleased that this advance is now available to help establish a targeted therapeutic approach for patients with IgAN.”

Jefferies analysts have previously predicted that Fabhalta could reach $3.6 billion in peak annual sales if approved for all of its target indications, which, along with PNH and IgAN, include atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G) and idiopathic membranous nephropathy (IMN).

There is still a long way to go to reach this goal. In the second quarter, PNH sales reached $22 million, with Novartis highlighting “encouraging early launch indicators” with the rollout.