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Novartis rides IgAN trioka to 2 trial wins in rare kidney diseases
28 May 2024
Clinical ResultPhase 3Drug ApprovalAccelerated ApprovalPriority Review
Novartis is developing three drugs against the kidney disease IgAN. In recent days, the company shared updates on two of them.
Novartis is eyeing an FDA filing for a second dkidney diseaselIgANin A nephropathy (IgAN), as the Swiss pharma goes all-in on the rare autoimmune kidney disease from three different angles.
Novartis plans to submFDAatrasentan to the FDA by the immunoglobulin A nephropathy (IgAN)ated approval in IgAN based on positive data fautoimmune kidney diseaseal. In the study, atrasentan led to a significant 36.1% relative reduction in proteinuria compared with placebo after 36 weeks of treatment, according to results presented at the European Renal Association Congress.
Novartisan could be a potatrasentanpetitor FDATravere Therapeutics’ rival drug Filspari (sparsentan). But IgANnalysts from William Blair and Leerink Partners suggested, the Novaratrasentanes not seem to have the upper hand.proteinuria
Heading into atrasentan’s 36-week readout, investors were expecting to see at least a 40% placebo-adjusted urine protein reduction because of earlier readouts based on small patient populations and shorter treatment periods, Leerink analysts pointed out in a Monday note.
The Novartis atrasentand off a 38.1% reduction in proteinuria, as measured by urine protein to creatinine ratio (UPCR), versus 3.1% for placebo. Both groups also received standard supportive care.Leerink
By cNovartisn, in the phase 3 PROTECT trial, Traveproteinuriari was associated with an average reduction in proteinuria of 49.8% after 36 weeks, compared with 15.1% for off-label irbesartan. This translates into a 41% relative reduction for Filspari.
The two drugs’ trials enrolled roughly similar populatiFilsparih some slight differences such as baseline UPproteinuria not likely to significantly change the outcome or interpretirbesartanesults, William Blair analysts wrote in a Tuesday noFilspariver, a notable difference in the percentage of Asian patients might be a confounding factor for a cross-trial comparison, the team added.
Despite the differences between the trials, atrasentan does not appear to be differentiated versus Filspari, Leerink’s analysts said. A recent Leerink survey suggested that doctors would split their use of Filspari and atrasentan equally.
Travere’s Filspari may have two advantages. atrasentanll, Filspari already boasts an accelerated apFilsparin Leerinknce February 2023, and TravLeerink already filed for a full approval with a target decisioFilsparin Sepatrasentanat gives Filspari a roughly two-year head start against Novartis’ atrasentan, the William Blair team noted.
Traverey, Filspari could reduce the number of pills patienFilsparito take, which is an important consideration for many with IgAN, Leerink Traveres noted. Filspari is a dual endothelin angiotensin receptor antagonist, while atrasentan inhFilsparie endothelin A receptor alone. FilspariNovartisniatrasentantes the need for an angiotensin receptor blocker such as irbesartan, which is part of the standard of care for IgAN.
However, hFilspariparate pills allows doctors to adjust the dose of each therapy for a patient, the Leerink team added. In thIgANd,Leerinking between the tFilsparilikely comeendothelin angiotensin receptorn, as well as whichatrasentans covered by pendothelin A receptorath to aFilsparition,” the Leerink analysts said.irbesartanIgAN
Filspari’s early launch has been progressing nicely, with about 2,000 patient start forms received bLeerinknd of March. The drug missed statistical significance on its confirmatory trial endpoint—change in estimated glomerular filtration rate (eGFR) slope, a measure of kidney function—in the PROLeerinkial. But Travere believes the results observed in the study could convince the FDA and doctors of its benefits.
Filspariirmatory evidence flop leaves a window open for Novartis’ atrasentan to potentially differentiate itself with an eGFR win. Atrasentan’s ALIGN study remains ongoing and blinded toward its final eGFR analysis, which is expected in 2026. Plus, Filspari is still only penetrating a very small corner of the IgAN at this stage, and there remains significant room for a competitorFDAillima Blair analysts aid.
IgAN troikaNovartisatrasentanAtrasentanFilspari
Atrasentan, which Novartis believes carries blockbuster potential, is one of the three drugs that the company is advancing in IgAN. Fabhalta, an oral factor B inhibitor, recently showed a 38.3% relative proteinuria reduction versus placebo in the phase 3 APPLAUSE-IgAN trial. The drug got its initial FDA approval in December for paroxysmal nocturnal hemoglobinuria (PNH), and Novartis has filed the IgAN indication with a decision now under priority review.
Atrasentan CongresNovartistis also shared phase 3 results for Fabhalta in an ultra-rare kidney disease called C3 glomerulopathIgANn FabhaltaAR-C3G stufactor B inhibitorot Fabhalta achieved a 35.1% reductproteinuriaeinuria compared with placebo after six months of treatment. Novartis plans to file forFDAe indication based on thatparoxysmal nocturnal hemoglobinuria (PNH) this Novartis this point, on the eGFR endpoint, Fabhalta showed a numerical improvement of 2.2mL/min/1.73m2.
Novartis has estimateNovartista could reach over $3 billion inFabhaltales across PNrare kidney diseaseC3 glomerulopathyFabhaltaproteinuriaNovartisFabhalta
WithIgANhalta, Novartis is targkidney diseasernative complement pathway. Overactivation of the pathway and deposition of the complement protein could cause kidney damage. So Fabhalta is intervening through that pathogenic mechanism of the injury, Aradhye explained.
AtrasFabhaltay Novartisg the endothelin receptor, inhibits excess proliferation and inflammatory signaling in mesangial cellscomplement proteined in IgAN.
Atrasentanagent, zigakibart, endothelin receptornti-APRIL antibody. Aradhye said the drug has the potential to be disease-modifying because it intervIgAN at an early stage when abnormal IgA is formed. Its phase 3 IgAN readout is expected in 2026, and Novartis also has blockbuster hopes for that drug.
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