Zigakibart

Novartis has kept Fabhalta’s list price unchanged at $550,000, which is much higher than the roughly $120,000 cost of Travere Therapeutics’ rival therapy Filspari. The first horse carrying Novartis’ immunoglobulin A nephropathy (IgAN) troika has crossed the FDA finish line.The FDA Wednesday granted an accelerated approval to Novartis’ Fabhalta in IgAN. The complement factor B inhibitor, plus the endothelin A receptor antagonist atrasentan and the anti-APRIL antibody zigakibart, are three drugs Novartis is developing for the rare autoimmune disease that attacks the kidney.Fabhalta got its initial FDA go-ahead in December 2023 for the ultrarare blood disease paroxysmal nocturnal hemoglobinuria (PNH). IgAN, though also a rare disease, is a larger indication that’s about 10 times the size of the PNH population.Still, Novartis has kept Fabhalta’s list price unchanged at $550,000, which is higher than the roughly $120,000 wholesale acquisition cost of Travere Therapeutics’ rival therapy Filspari.“We have considered the value of Fabhalta across all potential indications for which this innovative medicine is being studied,” Novartis said in a statement to Fierce Pharma. “This includes indications for both ultra-rare and rare diseases, some of which have no FDA-approved treatment options.”“Normally, when we set up the pricing, we already consider what is the different indications that we’re going to develop the therapy for and what is the appropriate price for those kinds of therapies and those kinds of indications,” Novartis’ U.S. president, Victor Bulto, said in an interview with Fierce Pharma ahead of the FDA approval. For Fabhalta, Novartis also benchmarked its price against other marketed complement inhibitors for various diseases, the company added in its statement. AstraZeneca’s C5 inhibitor Ultomiris, which is an infused antibody drug, also costs above $500,000 for several autoimmune diseases, including PNH. Fabhalta is an oral med.“Based upon the payer mix, the majority of Fabhalta patients will be commercially insured, and a significant number of commercially insured patients in the U.S. may pay as little as $0 for their copay,” Novartis said. As is the case with Filspari, Fabhalta’s accelerated approval is based on data showing it could reduce elevated protein levels in the urine, which is a sign of kidney damage.In the phase 3 APPLAUSE-IgAN study, Fabhalta pulled off a 38% placebo-adjusted reduction of proteinuria as measured by a urine protein-to-creatinine ratio at nine months. The reduction from baseline was 44% for the Novartis drug versus 9% in the control arm.The trial will continue to examine whether Fabhalta can slow kidney function decline as measured by estimated glomerular filtration rate (eGFR) decline over 24 months. Novartis now expects that endpoint to read out in 2025 to support a filing for a full FDA approval.While Fabhalta is the first of the three Novartis IgAN drugs to enter the market, atrasentan, which is under FDA review, is a more direct competitor to Travere’s Filspari given their similar mechanism. Filspari is an endothelin type A (ETA) and angiotensin receptor inhibitor. Atrasentan, which Novartis obtained from its Chinook Therapeutics buyout, is a selective ETA receptor antagonist.Because of their different mechanisms, Novartis believes each of its three drugs may be more or less relevant for patients with different disease presentations, Bulto explained, cautioning that the company is still looking for clinical evidence to confirm the differentiation.One hypothesis goes that if a patient is highly inflamed and has consistently high proteinuria, targeting the complement immune pathway with Fabhalta may be more appropriate, Bulto said. Before Filspari’s IgAN approval in early 2023, steroids and off-label use of angiotensin-targeting ACE inhibitors and ARBs were the only treatments for IgAN. Because Filspari already has an ARB mechanism, existing patients must stop their ARBs before taking the Travere therapy.Fabhalta takers don’t need to be taken off their ARB treatment, which, “from a continuity and from a simplicity perspective, is a good argument,” Bulto said.In another expected win for Novartis, Fabhalta doesn’t require regular monitoring of liver functions, whereas liver toxicity is included as a boxed warning for Filspari. Fabhalta carries its own boxed warning about the risk of potentially life-threatening infections caused by encapsulated bacteria.“If you have a compound that you can add on top of the current standard of care and that does not require continued monitoring, that would be a differentiated profile beyond proteinuria data,” Bulto said of Fabhalta.Meanwhile, Filspari is awaiting an FDA decision for a full approval in IgAN by Sept. 5. The drug previously missed statistical significance on its eGFR endpoint, but Travere is counting on consistent benefits observed across various metrics to convince the FDA.With Fabhalta’s launch in IgAN, Novartis will work with payers to ensure coverage and is offering a copay program to help those who cannot afford it, Bulto said. The company will also invest in raising awareness of the drug given that most patients and doctors prefer not to use steroids because of their long-term side effects, he added.Besides PNH and IgAN, Novartis is also testing Fabhalta in several other rare diseases, including C3 glomerulopathy, for which an FDA filing is being planned by the end of the year. Studies are ongoing for the drug in atypical hemolytic uremic syndrome, immune complex membranoproliferative glomerulonephritis and lupus nephritis.

Novartis announced Wednesday that the FDA granted accelerated approval to Fabhalta (iptacopan), to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at high risk of progression, marking the oral complement inhibitor’s second indication in the US following its earlier approval for paroxysmal nocturnal haemoglobinuria (PNH) in December.The decision positions Fabhalta as a strong competitor to Calliditas' Tarpeyo (budesonide) and Travere Therapeutics' Filspari (sparsentan) in the IgAN space, which were cleared by the FDA in 2021 and 2023, respectively. "Approval of Fabhalta as a first-in-class medicine for IgA nephropathy is an important milestone in our journey to evolve rare renal disease care by bringing new treatments to people in urgent need of options," remarked Victor Bultó, president of Novartis US.The expanded approval is backed by positive interim findings from the ongoing Phase III APPLAUSE-IgAN study, which randomised 470 adults with primary IgAN stabilised on RAS inhibitors, with or without SGLT2 inhibitors, to receive either twice-daily Fabhalta or placebo, both in combination with supportive care. The primary interim analysis endpoint was the percent reduction in proteinuria at nine months from baseline, measured on urine protein-to-creatinine ratio (UPCR).Results showed that proteinuria reduced by 44% in the Fabhalta group compared with 9% in the placebo group at nine months, translating to a clinically significant 38% reduction for Fabhalta versus placebo. Moreover, the benefit remained consistent across all subgroups, including age, sex, race, baseline disease characteristics, and SGLT2 inhibitor use. Novartis noted that the drug’s full approval will be contingent on the demonstration of a clinical benefit in slowing disease progression, assessed by glomerular filtration rate (eGFR) decline over 24 months. The eGFR data is likely to readout next year upon study completion. Similar to its earlier indication, the company stated that Fabhalta will only be available through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria.The drugmaker’s IgAN pipeline also includes two other therapies: atrasentan, an oral endothelin A receptor antagonist currently under FDA review after succeeding in the Phase III ALIGN trial, and zigakibart, a subcutaneous anti-APRIL monoclonal antibody in late-stage development. Meanwhile, Fabhalta is also being investigated in C3 glomerulopathy, where it met the main goal of the Phase III APPEAR-C3G trial.