Sobi and Apellis report positive top-line results at 48 weeks from the phase III PEGASUS study of pegcetacoplan in paroxysmal nocturnal haemoglobinuria.

Swedish Orphan Biovitrium (SOBI) and Apellis Pharmaceuticals Inc.announced positive top-line results at week 48 from the phase III PEGASUS study, which demonstrated sustained haematological and clinical improvements in patients with paroxysmal nocturnal haemoglobinuria (PNH) who were treated with pegcetacoplan, an investigational, targeted C3 therapy. The safety profile of pegcetacoplan was consistent with previously reported data and no new safety signals were identified. All patients (n=77) 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, haemoglobin 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 haemoglobin and other haematological and clinical measures, similar to patients treated with pegcetacoplan monotherapy during the randomized controlled period. In addition to a sustained improvement in haemoglobin, patients treated with pegcetacoplan maintained improvements across key secondary endpoints . Throughout the 48-week study, 73 per cent 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. Overall, the safety profile of pegcetacoplan was consistent with previously reported data throughout the 48-week study. 24 of 80 pegcetacoplan monotherapy-treated patients (30 per cent) experienced a serious adverse event (SAE); five of the SAEs (6 per cent) 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. The most common adverse events (AEs) reported throughout the study were injection site reactions (36 per cent), haemolysis (24 per cent), and diarrhoea (21 per cent). 12 out of 80 patients (15 per cent) discontinued due to adverse events, with five discontinuations due to haemolysis. 64 of the 67 patients (96 per cent) who completed the open-label period opted to enter the extension study. Marketing applications for pegcetacoplan for the treatment of PNH are under review by the FDA and the 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. Detailed data will be presented at a future medical congress.