RARE Daily

Apellis and Sobi Report Therapy Demonstrated Sustained Improvement in Late-Stage PNH Study

December 10, 2020

Rare Daily Staff

Apellis Pharmaceuticals and Sobi Swedish Orphan Biovitrum reported top-line results at week 48 from their phase 3 study of their experimental therapy pegcetacoplan in the rare blood disorder paroxysmal nocturnal hemoglobinuria, which showed sustained hematological and clinical improvements in patients.

Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, life-threatening disorder characterized by the destruction of oxygen-carrying red blood cells through extravascular and intravascular hemolysis. Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue, hemoglobinuria and difficulty breathing (dyspnea).

Pegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b.

Pegcetacoplan is being evaluated in several clinical studies across hematology, ophthalmology, nephrology, and neurology.

The 77 patients who completed the 16-week randomized controlled period of the PEGASUS study, which evaluated pegcetacoplan compared to eculizumab, entered the open-label period and received pegcetacoplan from Week 17 to Week 48.

At Week 48, hemoglobin increases were sustained in pegcetacoplan-treated patients with a mean improvement from baseline of 2.7 g/dL, which is equal to the 2.7 g/dL mean increase seen at Week 16 with pegcetacoplan-treated patients. Additionally, eculizumab-treated patients who switched to pegcetacoplan during the open-label period experienced sustained improvements in hemoglobin and other hematological and clinical measures, similar to patients treated with pegcetacoplan monotherapy during the randomized controlled period.

“These long-term results show that pegcetacoplan has the potential to help patients with PNH gain and maintain more complete control of the disease,” said Federico Grossi, chief medical officer of Apellis. “The sustained hematologic and quality-of-life improvements and consistent safety profile of pegcetacoplan observed in this study adds to a growing body of evidence that demonstrates the potential of this investigational, targeted C3 therapy to elevate the standard of care and improve the lives of people with PNH.”

In addition to a sustained improvement in hemoglobin, patients treated with pegcetacoplan maintained improvements across key secondary endpoints. Throughout the 48-week study, 73 percent of patients treated with pegcetacoplan remained transfusion free. For comparison, 25 percent of patients were transfusion free over the year prior to entering the PEGASUS study while on treatment with eculizumab. Improvements across additional markers of disease, such as reticulocyte count, lactate dehydrogenase (LDH) levels, and the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue scores, were maintained.

The safety profile of pegcetacoplan was consistent with previously reported data, and no new safety signals were identified. Twenty-four of 80 pegcetacoplan monotherapy-treated patients (30 percent) experienced a serious adverse event; five of the serious adverse events were assessed to be possibly related to study treatment. No cases of meningitis were reported. One death was reported due to COVID-19 and was unrelated to study treatment.

Twelve out of 80 patients (15 percent) discontinued due to adverse events, with five discontinuations due to hemolysis.

“Despite existing treatments, many patients with PNH continue to suffer from persistently low hemoglobin, which can lead to a need for frequent transfusions and debilitating fatigue,” said Ravi Rao, head of R&D and chief medical officer at Sobi. “The long-term data suggest that pegcetacoplan, if approved, has the potential to provide meaningful and durable benefits to these patients with high unmet medical need.”

Marketing applications for pegcetacoplan for the treatment of PNH are under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA granted the application Priority Review designation and set a target action date of May 14, 2021. An opinion from the Committee for Medicinal Products for Human Use (CHMP) is expected in 2021.

Photo: Federico Grossi, chief medical officer of Apellis


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