Travere weaker after Filspari fails confirmatory trial

Shares in Travere Therapeutics have lost more than 40% of their value after the company said that a trial designed to confirm the benefits of its recently approved Filspari drug for rare kidney disease IgA nephropathy (IgAN) fell short.

Despite the miss in the phase 3 study, Travere said the “totality of data” from the PROTECT trial supported the efficacy of Filspari (sparsentan), which was given accelerated approval for IgAN by the FDA in February.

It remains to be seen whether the FDA will share that appraisal and allow the drug to stay on the market, but Travere said it remains confident in the programme and will continue as planned with a filing next year to convert its accelerated approval into a full, permanent license.

Filspari was launched as a rival to Calliditas’ corticosteroid-based Tarpeyo (budesonide) therapy, which became the first FDA-approved therapy for IgAN in 2021. Calliditas shares rose more than 16% in the wake of Travere’s announcement.

Both drugs were given accelerated approval on the back of clinical results showing they were able to reduce protein levels in the urine of IgAN patients, a surrogate marker, as additional trials try to establish whether that translates to a decline in kidney function that characterises the disease, measured by the estimated glomerular filtration rate (eGFR).

Calliditas has already filed to upgrade Tarpeyo to a full approval based on the results of the NefIgArd study, with a decision due from the FDA by 20th December after a priority review.

The PROTECT study – which led to Filspari’s approval based on proteinuria results – failed to meet statistical significance on a secondary endpoint of improved eGFR total slope compared to control therapy irbesartan, although Travere said a “clinically meaningful” difference in the rate of decline was seen.

There was a trend towards improvement with Filspari as well as significant improvements on other endpoints, including eGFR chronic slope, which is the main secondary endpoint of interest to the regulatory authority in the EU, where Filspari has also been filed for approval.

“The confirmatory results of the PROTECT Study demonstrated treatment with Filspari resulted in the largest sustained reduction in proteinuria and one of the slowest rates of eGFR decline in a controlled study of IgAN patients to date,” said Travere’s chief executive Eric Dube.

He maintained that despite the miss on eGFR total slope – the FDA’s preferred confirmatory endpoint – the “overall evidence from PROTECT suggests potential long-term benefit of Filspari as a foundational treatment for patients with IgAN”.

Earlier this year, Filspari also failed to meet its objectives in a pivotal trial in focal segmental glomerulosclerosis (FSGS), another rare kidney disease, in which the comparator drug was also irbesartan.

The drug, a first-in-class antagonist of both endothelin type A (ETA) and angiotensin II subtype 1 (AT1) receptors, was one of Clarivate’s top drugs to look out for in 2023 as potential future blockbusters.