Novartis Secures Phase III Fabhalta Win in IgAN as FDA Starts Priority Review

 Novartis on Monday announced Phase III trial results for its potential multibillion-dollar drug Fabhalta (iptacopan), linking the molecule to improvements in kidney disease patients as it races toward accelerated approval.

The Swiss drugmaker said the Phase III study met its pre-specified interim analysis primary endpoint in October 2023. However, while Novartis said IgA nephropathy (IgAN) patients had a statistically significant and clinically meaningful reduction in proteinuria—the medical term for a high level of protein in urine— after taking Fabhalta, it kept the numbers to itself.

Monday, the company finally shared the figures behind the hit on the primary endpoint, revealing that patients treated with Fabhalta had a 38.3% proteinuria reduction at nine months compared to placebo. The 518 patients enrolled in the study received Fabhalta or placebo in addition to supportive care.

Novartis filed for accelerated FDA approval using the data and was accepted for priority review. The drug developer has yet to share the deadline for the approval decision but the six-month timeline for priority review suggests the FDA will rule on the application in the second half of 2024.

So far, the Phase III study has linked Fabhalta to reduced proteinuria without confirming the therapy has a positive effect on kidney function. In recent years, the FDA has granted accelerated approval of IgAN drugs from Calliditas Therapeutics and Travere Therapeutics based on proteinuria data. Researchers have found a strong relationship between proteinuria and loss of kidney function.

Travere brought Filspari (sparsentan) to market in IgAN after linking the treatment to a 45% proteinuria reduction at week 36, compared to a 15% decline in the irbesartan control group. The FDA authorized Calliditas’ Tarpeyo after reviewing the results of a study that found it reduced proteinuria by 34% over nine months, versus a 5% decline in the placebo arm.

Novartis’ Phase III study remains blinded as the company gathers data on its second primary endpoint, which is looking at a measure of kidney function over 24 months. The company expects to complete the trial and get data on the second primary endpoint in 2025.

Accelerated approval in IgAN is part of a plan that Novartis said could lead to multibillion-dollar sales of Fabhalta. The FDA approved the drug in adults with paroxysmal nocturnal hemoglobinuria in December 2023 but Novartis CEO Vas Narasimhan told investors to expect “a modest ramp” in the indication on an earnings call in January 2024. Narasimhan predicted “very strong uptake” of the medicine in IgAN and C3 glomerulopathy, an progressive kidney disease in which Novartis has reported Phase III data.

Fabhalta is part of a broader push to treat IgAN. Novartis acquired the endothelin receptor antagonist atrasentan and anti-APRIL antibody zigakibart in its $3.2 billion takeover of Chinook Therapeutics. Both candidates are in Phase III.

https://www.biospace.com/article/novartis-secures-phase-iii-fabhalta-win-in-igan-as-fda-starts-priority-review/