FDA/CDC

FDA greenlights iptacopan to treat paroxysmal nocturnal hemoglobinuria


 

The US Food and Drug Administration (FDA) has approved iptacopan (Fabhalta, Novartis), the first oral monotherapy for both treatment-naive and pretreated adults with paroxysmal nocturnal hemoglobinuria (PNH).

Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.

Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.

The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.

APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).

The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.

In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.

In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.

“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.

A version of this article appeared on Medscape.com.

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