Otsuka eyes early filing of IgAN drug after phase 3 readout

Otsuka is hoping to file for approval of its anti-APRIL antibody sibeprenlimab as a treatment for kidney disorder IgA nephropathy (IgAN) after the drug hit the target in a phase 3 trial.

The Japanese drugmaker said that interim results from the 530-patient VISIONARY study showed that sibeprenlimab achieved a statistically significant and clinically meaningful reduction in 24-hour urine protein-to-creatine ratio (uPCR) – a measure of how well the kidneys are working – after nine months of treatment.

In a statement, Otsuka said it will review the data with the FDA to see if it can "enable a potential regulatory submission for accelerated approval," with final results from the study expected in early 2026. The US regulator has awarded sibeprenlimab breakthrough status on the strength of encouraging results in an earlier phase 2 trial called ENVISION.

IgAN is a rare autoimmune kidney disorder and a leading cause of kidney failure, in which antibodies accumulate in the kidneys, causing inflammation and scarring. The disease affects around 130,000 people in the US and another 115,000 in Europe.

John Kraus, Otsuka's chief medical officer, said the results suggest sibeprenlimab could provide "a new therapeutic strategy for people living with this progressive kidney disease." The antibody was originated by Otsuka's US affiliate Visterra, which it acquired in 2018 for $430 million.

Otsuka's readout comes as competition in the APRIL category is shaping up to be quite intense, with a number of other candidates in late-stage clinical testing.

Novartis also has an anti-APRIL antibody called zigakibart in phase 3 trials, while Vertex Pharma has a dual antagonist of BAFF and APRIL, povetacicept, which it acquired as part of its takeover of Alpine Pharma and is due to start phase 3 trials in the disorder later this year. Also in the running is Vera Therapeutics, whose APRIL and BLyS-targeting candidate atacicept is also in late-stage testing.

Meanwhile, zigakibart is just one of three drugs Novartis is developing for IgAN, which had no therapies available until Calliditas' corticosteroid-based Tarpeyo (budesonide) therapy was approved in 2021.

Novartis already has approval for targeted factor B inhibitor Fabhalta (iptacopan) – tipped to become a blockbuster – while oral ETA receptor antagonist atrasentan had promising results in a phase 3 trial and is scheduled to be filed this year. Another new entrant is Travere/CSL's ETA and AT1 receptor antagonist Filspari (sparsentan), which got accelerated approval from the FDA in February 2023 and was upgraded to a full approval in September.