Apellis announced positive results from PEGASUS, its phase 3 head-to-head study of pegcetacoplan (APL-2) compared to eculizumab in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). Pegcetacoplan met the primary endpoint of superiority compared to eculizumab on hemoglobin levels.
PEGASUS was a multi-center, randomized, open-label, active-comparator controlled study in 80 adults with PNH. All patients were on eculizumab (stable for at least 3 months) with a hemoglobin level of <10.5 g/dL at the screening visit. During the four-week run-in, patients were dosed with 1080 mg of pegcetacoplan twice weekly in addition to their current dose of eculizumab. During the 16-week randomized, controlled period, patients were randomized to receive either 1080 mg of pegcetacoplan twice weekly or their current dose of eculizumab. All patients completing the randomized controlled period entered the open-label pegcetacoplan treatment period where they received pegcetacoplan, regardless of the prior treatment received in the randomized, controlled period.
Top-line data show that pegcetacoplan met the study’s primary efficacy endpoint, demonstrating superiority to eculizumab with a statistically significant improvement in adjusted means of 3.8 g/dL of hemoglobin at week 16 (p<0.0001). At week 16, pegcetacoplan-treated patients (n=41) had an adjusted mean hemoglobin increase of 2.4 g/dL from a baseline of 8.7 g/dL, compared to eculizumab-treated patients (n=39) who had a change of -1.5 g/dL from a baseline of 8.7 g/dL.
Pegcetacoplan also showed promising results in key secondary endpoints. Pegcetacoplan met non-inferiority on transfusion avoidance and absolute reticulocyte count. Pegcetacoplan also showed positive trends on lactate dehydrogenase (LDH) and fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue score.
The most common adverse reactions were injection site reactions, diarrhea, headache and fatigue. In addition, hemolysis was reported in four patients in the pegcetacoplan group (9.8%) and nine patients in the eculizumab group (23.1%). This led to the three discontinuations in pegcetacoplan group.
About pegcetacoplan (APL-2)
Pegcetacoplan is a targeted C3 inhibitor designed to regulate excessive complement activation, 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 was granted Fast Track designation by the U.S. FDA for the treatment of PNH and the treatment of geographic atrophy.
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH is a rare, chronic, life-threatening blood disorder associated with abnormally low hemoglobin levels due to the destruction of oxygen-carrying red blood cells (hemolysis). Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue and difficulty breathing (dyspnea). Retrospective studies show that, even on eculizumab, approximately 70% of people with PNH have low hemoglobin levels, and 36% require one or more transfusions a year.