Novartis ups the ante in AstraZeneca blood disorder showdown with fresh data

Novartis’ pursuit of the crown jewels of AstraZeneca’s $39 billion Alexion buyout is gathering pace. The latest data show more than 90% of participants in a phase 3 trial experienced the hoped-for improvement after taking the oral factor B inhibitor, boosting the Swiss drugmaker’s prospects of creating a new standard of care in a rare blood disorder. 

Late last year, Novartis revealed that the phase 3 APPOINT-PNH study met its primary endpoint. In the study, patients with paroxysmal nocturnal hemoglobinuria (PNH) who had never taken complement inhibitors such as AstraZeneca’s Soliris and Ultomiris were given Novartis' oral drug candidate iptacopan. Days later, iptacopan blew Soliris out of the water in a different head-to-head clinical trial.

Now, Novartis has shared a look at the data from APPOINT-PNH. An estimated 92.2% of patients had a 2 g/dL or more hemoglobin-level increase from baseline without the need for red blood cell transfusions after the 24-week core treatment period. Novartis estimated the figure to account for missing data. 

The proportion of responders is higher than in the head-to-head clinical trial. In the earlier trial, Novartis enrolled patients who had residual anemia despite a stable regimen of anti-C5 therapy in the prior six months and randomized them to receive iptacopan or one of AstraZeneca’s PNH blockbusters. In that trial, 80% of patients on iptacopan met the response criteria, compared to 2% in the active control arm.

Novartis also shared a look at secondary endpoints from APPOINT-PNH. An estimated 62.8% of patients had hemoglobin levels of 12 g/dL or more without the need for red blood cell transfusions. And an estimated 97.6% of patients achieved red blood cell transfusion independence at 24 weeks. In contrast, 70% of patients received blood transfusions in the six months prior to treatment.

The results strengthen Novartis’ pitch to establish iptacopan as the standard of care in PNH. A filing for approval is awaiting acceptance at the FDA. With Novartis seeking priority review, the drug candidate could win approval by the end of the year. Roche is nearing approval in PNH, too, suggesting that the indication may be on the cusp of its biggest shake-up since Alexion established the market years ago.

Novartis plans to target multiple groups of patients. Talking to investors earlier this year, Novartis CEO Vas Narasimhan voiced a belief that “60% to 70% of patients who, on current anti-C5 based therapies, are not adequately controlled” and could be switched to iptacopan. Novartis also plans to target the 60% to 70% of diagnosed PNH patients who aren’t on therapy but may be interested in treatment.

Based on the size of the opportunities, both in PNH and other indications, Novartis sees iptacopan as a $3 billion-a-year drug. AstraZeneca is working to deny Novartis the opportunities and keep hold of the market, including by advancing its own oral factor D inhibitors.