Novartis builds case for iptacopan as oral rival to PNH injectables

Novartis has a second positive phase 3 trial in the bag for its targeted factor B inhibitor iptacopan, vying to become an oral alternative to injectable therapies for ultra-rare blood disorder paroxysmal nocturnal haemoglobinuria (PNH).

The Swiss pharma group said this morning that the top-line results of the APPOINT-PNH trial showed that iptacopan provided “clinically meaningful” increases in haemoglobin levels in patients with PNH who had not previously been treated with injectable complement C5 inhibitors like AstraZeneca/Alexion’s Soliris (eculizumab) and Ultomiris (ravulizumab).

In the trial, a significant proportion of patients treated with iptacopan (200 mg twice daily) achieved clinically meaningful haemoglobin-level increases of 2 g/dL or more from baseline without the need for blood transfusions at 24 weeks.

The earlier APPLY-PNH study – reported in October – was carried patients who were still experiencing residual anaemia despite prior treatment with anti-C5 antibodies and showed that iptacopan was more effective than the C5 inhibitors at helping them to meet target haemoglobin levels.

Armed with both trial results, Novartis says it now intends to press ahead with plans to file for regulatory approval of iptacopan next year.

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 PNH, include atypical haemolytic uraemic syndrome (aHUS) and rare kidney diseases C3 glomerulopathy (C3G) and idiopathic membranous nephropathy (IMN).

In PNH, the body’s complement system destroys red blood cells leading to anaemia, fatigued and in some cases needing blood transfusions. It is estimated that approximately 10-20 people per million worldwide live with PNH. It can develop at any age, though is often diagnosed in people between 30-40 years old.

Between 20% and 50% of PNH patients treated with Soliris or other drugs in the C5 inhibitor class can’t get symptoms under control and require blood transfusions, so there’s a clear need for new treatment options.

In PNH and aHUS, iptacopan will compete with Soliris and Ultomiris, but it could become the first treatment for C3G and IMN if approved.