FDA Approval to Fabhalta: A New Era in Treatment of the Rare Blood Disorder PNH

Novartis announced that the FDA has granted approval to Fabhalta for adults with paroxysmal nocturnal hemoglobinuria (PNH). This oral monotherapy, with its remarkable efficacy and safety profile, offers hope to PNH patients by improving hemoglobin levels and reducing the need for blood transfusions. Novartis aims to make Fabhalta available in the US in December.

In a significant development, the U.S. Food and Drug Administration (FDA) has granted approval for Novartis' new drug, Fabhalta (iptacopan), as an oral monotherapy for suffering from paroxysmal nocturnal hemoglobinuria (PNH). The approval is based on the Phase III APPLY-PNH trial, where Fabhalta demonstrated notable efficacy in clinical trials, including a transfusion avoidance rate of 95.2% for patients with prior anti-C5 treatment.

This development marks a significant milestone for PNH patients and represents a transformative advancement in the treatment of this rare blood disorder.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH. In clinical studies, iptacopan was superior to anti-C5s in hemoglobin improvement in the absence of RBC transfusion and transfusion avoidance rate, and also effective in complement inhibitor-naïve individuals, by providing clinically meaningful hemoglobin-level increases without the need for blood transfusions,” said Professor Vinod Pullarkat, Department of Hematology, City of Hope.

Understanding the Impact of PNH

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the premature destruction of red blood cells by the body's complement system, leading to anemia, blood clots, and other distressing symptoms. Until now, treatment options for PNH primarily revolved around anti-C5 drugs like Soliris and Ultomiris, which required infusion administration. These therapies often left a substantial proportion of patients with unresolved anemia and dependent on blood transfusions. People who take Fabhalta don't need to get blood transfusions.

Superior Hemoglobin Improvement

The FDA's approval was based on data from two late-stage trials: APPLY-PNH and APPOINT-PNH. APPLY-PNH focused on patients with residual anemia despite prior anti-C5 treatment, while APPOINT-PNH included complement inhibitor-naïve patients.

In APPLY-PNH, patients who switched to Fabhalta experienced substantial increases in hemoglobin levels, with 82.3% of anti-C5-experienced Fabhalta patients achieving an increase of ≥ 2 g/dL compared to 0% of those on anti-C5 treatment. Similarly, 67.7% of Fabhalta patients maintained hemoglobin levels ≥ 12 g/dL compared to none in the anti-C5 group.

Furthermore, the drug exhibited remarkable success in transfusion avoidance, with a transfusion avoidance rate of 95.2% for anti-C5-experienced Fabhalta patients compared to 45.7% for those on anti-C5 treatment.

Safety Profile

Fabhalta demonstrated a good safety profile in both trials, with the most common side effects being headache, nasopharyngitis, diarrhea, abdominal pain, and infections. Notably, patients who received Fabhalta did not require blood transfusions, a critical advancement in the treatment of PNH. However, it's worth mentioning that the FDA has mandated a risk management plan for Fabhalta that includes vaccinations for encapsulated bacteria to mitigate the risk of serious infections.

A Paradigm Shift in PNH Treatment

Fabhalta represents a significant step forward in PNH treatment, offering a convenient, oral monotherapy option with compelling efficacy. It's important to note that this Factor B inhibitor targets the immune system's complement pathway, addressing both intra- and extravascular hemolysis comprehensively. This approach differentiates Fabhalta from existing anti-C5 therapies, providing new hope for patients who have long struggled with the disease's debilitating symptoms.