RARE Daily

FDA Approves Novartis Oral Therapy for PNH

December 6, 2023

Rare Daily Staff

The U.S. Food and Drug Administration approved Novartis’ Fabhalta, the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare, autoimmune disease.

PNH is a chronic and serious complement-mediated blood disorder. People with PNH have an acquired mutation in some of their hematopoietic stem cells in the bone marrow and can give rise to red blood cells that are susceptible to premature destruction by the complement system. This leads to destruction of red blood cells within blood vessels, spleen, and liver. It can cause anemia, the formation of blood clots, and other debilitating symptoms.

Fabhalta is a Factor B inhibitor that acts proximally in the alternative complement pathway of the immune system, providing comprehensive control of red blood cell destruction within and outside the blood vessels. In clinical trials, treatment with Fabhalta increased hemoglobin levels in the majority of patients and in APPLY-PNH nearly all patients treated with Fabhalta did not receive blood transfusions.

The FDA approval is based on the phase 3 APPLY-PNH trial in patients with residual anemia despite prior anti-C5 treatment who switched to Fabhalta, which demonstrated superiority in hemoglobin improvement in the absence of red blood cell transfusions and in transfusion avoidance rate over patients who stayed on anti-C5 treatments. Approval was also supported by the phase 3 APPOINT-PNH study in complement inhibitor-naïve patients.

The studies showed patients experienced a sustained increase of hemoglobin levels ≥ 2 g/dLa from baseline in the absence of transfusions (82.3 percent of anti-C5-experienced Fabhalta patients responded vs. 0 percent for anti-C5 in the APPLY-PNH study and 77.5 percent in the APPOINT-PNH study)

Patients also demonstrated a sustained hemoglobin level ≥ 12 g/dLa in the absence of transfusions (67.7 percent of anti-C5-experienced Fabhalta patients responded vs. 0 percent).

And patients avoiding transfusions reached 95.2 percent for anti-C5-experienced Fabhalta patients vs. 45.7 percent for anti-C5 patients.

The most commonly reported (≥10 percent) adverse reactions with Fabhalta vs. anti-C5s were: headache (19 percent vs. 3 percent), nasopharyngitis (16 percent vs. 17 percent), diarrhea (15 percent vs. 6 percent), abdominal pain (15 percent vs. 3 percent), bacterial infection (11 percent vs. 11 percent), nausea (10 percent vs. 3 percent), and viral infection (10 percent vs. 31 percent).

In APPLY-PNH, serious adverse events were reported in two (3 percent) patients with PNH receiving Fabhalta, which included pyelonephritis, urinary tract infection and COVID-19. In APPOINT-PNH, serious ARs were reported in two (5 percent) patients with PNH receiving Fabhalta, which included COVID-19 and bacterial pneumonia. The most commonly reported ARs (≥10 percent) were headache (28 percent), viral infection (18 percent), nasopharyngitis (15 percent), and rash (10 percent).

Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy that requires vaccinations for encapsulated bacteria.

“The U.S. approval of Fabhalta is an extraordinary moment for people living with PNH, their loved ones and the healthcare providers who care for them,” said Victor Bultó, president of U.S. for Novartis. “This new, effective oral medicine may mean that patients can reset their expectations of living with PNH, a chronic and life-altering blood disease.”



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