New extended data show Fabhalta keeps working for nearly 1 year

PNH patients sustain near-normal hemoglobin levels with approved therapy

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Taking Novartis’ Fabhalta (iptacopan) as a monotherapy — meaning as a sole treatment — twice daily for almost one year continued to sustain hemoglobin at near-normal levels, generally without the need for blood transfusions, in adults with paroxysmal nocturnal hemoglobinuria (PNH).

These new data come from an open-label extension for patients who completed the first 24 weeks, or nearly six months, of the APPLY-PNH (NCT04558918) clinical trial. The initial Phase 3 study showed that Fabhalta outperforms standard of care in treating the rare acquired disease.

The U.S. Food and Drug Administration (FDA) approved Fabhalta earlier this month to treat adults with PNH, regardless of whether they have been previously treated or have received no prior treatment for their disease.

“Coming on the heels of Fabhalta’s recent approval in PNH, these extended data … reinforce Fabhalta’s utility as an important new oral monotherapy for people living with PNH,” David Soergel, MD, global head of cardiovascular, renal, and metabolism development unit at Novartis, said in a company press release.

Novartis has filed additional regulatory applications elsewhere, with Soergel now noting that the company is “eager to bring this novel treatment to even more people living with rare complement-driven disorders as we pursue several additional indications for Fabhalta.”

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FDA approves Fabhalta as first oral therapy for PNH

Trial participants had option to continue on now-approved therapy

PNH occurs when red blood cells become a target of attack by the complement system, a part of the immune system to remove damaged cells from tissues and protect the body against infection.

The first medications approved to treat PNH work by inhibiting either the C3 or the C5 complement proteins, preventing hemolysis — the breakdown of red blood cells — by the complement system. While this is expected to help relieve the symptoms of PNH, not everyone responds as well to C3 or C5 inhibitors.

Fabhalta is designed to inhibit factor B, a complement protein that acts upstream of C3 and C5. By targeting this earlier step of the complement system, Fabhalta is thought to be able to prevent hemolysis occurring both inside and outside of blood vessels.

The goal of APPLY-PNH was to test the safety and efficacy of hard gelatin capsules containing 200 mg of Fabhalta in adults with PNH who were randomly assigned to either switch from the C5 inhibitor Soliris (eculizumab) or Ultomiris (ravulizumab) or continue taking their standard of care.

The proportion of Fabhalta-treated patients who had an increase of 2 g/dL or more of hemoglobin was 82.3%, compared with none on standard of care. Hemoglobin is the protein that carries oxygen in red blood cells.

Also, 67.7% of participants on Fabhalta had near-normal hemoglobin levels of at least 12 g/dL (68.8% vs. 1.8%), again versus none in the other group.

After 24 weeks, patients could opt to enter an extension period where they continued to receive treatment with Fabhalta for an additional 24 weeks (for a total of 48 weeks, or about 11 months) or switched from standard of care to treatment with Fabhalta.

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No blood transfusions for over 90% of patients on Fabhalta

Among the 61 patients who took Fabhalta for a total of 48 weeks, hemoglobin had increased by a mean 3.35 g/dL and continued at near-normal mean levels (12.2 g/dL). The majority (91.9%) of patients remained free of blood transfusions.

They also showed improvements in patient-reported fatigue, as observed by a 9.8-point increase in the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) score, indicating less fatigue during usual daily activities.

The 34 patients who switched from standard of care with a C5 inhibitor to Fabhalta achieved outcomes similar to those on Fabhalta for a total of 48 weeks, including mean hemoglobin at near-normal levels (12.1 g/dL). Most (94.1%) remained free of blood transfusions, and mean FACIT-F score increased by 10.8 points.

Our findings continue to support oral [Fabhalta] monotherapy as a potentially practice-changing treatment for hemolytic PNH.[/quote

Fabhalta was well tolerated, and its safety profile was similar at 24 and 48 weeks. There were no severe or serious side effects deemed related to treatment with Fabhalta. Despite an increased chance of getting a serious bacterial infection, no such infection was reported.

“Our findings continue to support oral [Fabhalta] monotherapy as a potentially practice-changing treatment for hemolytic PNH,” the researchers wrote in an abstract for a presentation at the 65th American Society of Hematology Annual Meeting & Exposition, held Dec. 9–12 in San Diego.

“The new APPLY-PNH data are an expansion of the robust outcomes we saw in the randomized phase and demonstrate that patients with PNH who took Fabhalta experienced meaningful hemoglobin improvement over the longer term – nearly a year,” said Antonio Risitano, MD, PhD, one of the trial’s investigator.

“Additionally, the new data confirm that these benefits may occur within weeks after switching from [C5 inhibitors]. The APPLY-PNH findings continue to confirm Fabhalta as a promising therapeutic option for people living with PNH,” said Risitano, who also is president of the International PNH Interest Group.