CSL, Travere close on EU approval of IgAN drug sparsentan

Travere Therapeutics and partner CSL Vifor could be weeks away from EU approval of sparsentan for IgA nephropathy, after getting a positive opinion on the drug from the EMA’s human medicines committee.

The CHMP has recommended approval of sparsentan for the treatment of primary IgAN – a rare kidney disorder and a leading cause of kidney failure – in adults with a urine protein excretion above 1 g/day or a urine protein-to-creatinine ratio of 0.75 g/g or more.

The decision puts Travere and CSL in line for a first-in-class approval in IgAN for sparsentan, an oral antagonist of both endothelin type A (ETA) and angiotensin II subtype 1 (AT1) receptors, which are associated with the progression of kidney disease.

Based on an estimated prevalence of around 2.5 cases per 10,000 people, there are thought to be around 115,000 cases in the EU of the autoimmune disease, also known as Berger’s disease, which occurs when antibodies accumulate in the kidneys, causing inflammation and scarring.

The drug – already granted accelerated approval as Filspari in the US – was highlighted by Clarivate last year among its list of new products that have the potential to either become $1 billion-plus sellers by 2027 or change clinical practice.

Filspari was approved by the FDA on the strength of data from the pivotal PROTECT study, which showed it could reduce protein levels in the urine of IgAN patients, a surrogate marker. Prospects were dented, however, when the drug failed to significantly improve the estimated glomerular filtration rate (eGFR), considered a better marker of kidney function.

Travere has said, though, that it is confident that the totality of the data will support full approval, and plans to file the data with the FDA in the first quarter of this year. It notes that PROTECT is the only head-to-head study in IgAN against a maximally labelled dose of angiotensin 2 receptor antagonist irbesartan, a current standard of care.

The company launched Filspari at a discount to Calliditas’ corticosteroid-based Tarpeyo (budesonide) therapy, which became the first FDA-approved therapy for IgAN in 2021 and made sales of $104 million in 2023.

Travere – which sells Filspari on its own in the US and licenses it to CSL Vifor in Europe, Australia, and New Zealand - said last week that it had booked $15 million from the product in the fourth quarter and $29 million since its launch in February.

Both Filspari and Tarpeyo could see a challenge in the IgAN market from Novartis’ targeted factor B inhibitor iptacopan, which showed efficacy at reducing proteinuria in an interim analysis of the phase 3 APPLAUSE-IgAN trial reported last year. Final results from that study are due next year, but Novartis has been discussing with the FDA whether it may be able to file early on the current dataset.

Analysts at Jefferies have previously said that iptacopan could hit $3.6 billion in peak annual sales if it gets approved for all its target indications, which, along with IgAN, include paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS), C3 glomerulopathy (C3G), and idiopathic membranous nephropathy (IMN).

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