New drugs for rare diseases! Apellis C3 inhibitor pegcetacoplan head to head phase III study beat alexion C5 inhibitor soliris

January 9, 2020 / bioun / -- apellis Pharmaceutical Co., Ltd is committed to developing the first and best of its kind therapies through the pioneering targeting C3 method, which are used to treat a wide range of diseases driven by uncontrolled or excessive activation of complement cascade reaction, including hematology, ophthalmology and nephrology Recently, the company announced the positive results of the head to head phase III Pegasus study (apl2-302, nct03500549) (see Pegasus phase 3 top line results conference call presentation for details) The study was a multicenter, randomized, open label, positive drug control, head-to-head study in 80 adult patients with paroxysmal nocturnal hemoglobinuria (PNH) The efficacy and safety of pegcetacopolan (APL-2) compared with soliris (eculizumab) were evaluated Soliris, a heavy-duty C5 complement inhibitor from alexion, has been approved for the treatment of PNH In this study, subjects were required to be treated with eculizumab at all times (stable treatment for at least 3 months) and had hemoglobin levels < 10.5g/dl at the time of the screening visit For another 4 weeks, the patients received 1080mg of pegcetacopolan twice a week and the current dose of eculizumab During the 16 week randomized control period, patients were randomly assigned to receive 1080mg of pegcetacoplan (twice a week) or their current dose of eculizumab All the subjects who completed the randomized control period entered the open label pegcetacopolan treatment period and received pegcetacopolan treatment without considering the treatment scheme in the randomized control period The results showed that the study reached the main efficacy end point: compared with eculizumab, pegcetacopolan had a statistically significant improvement (P < 0.0001) in hemoglobin corrected mean value of 3.8g/l at the 16th week of treatment At the 16th week of treatment, the adjusted mean hemoglobin level of pegcetacopolan patients (n = 41) increased by 2.4g/dl compared with the baseline of 8.7g/dl, and the adjusted mean hemoglobin level of eculizumab patients (n = 39) changed by - 1.5g/dl compared with the baseline of 8.7g/dl Pegcetacoplan also showed promising results at critical secondary endpoints Pegcetacoplan achieved non inferiority in avoiding blood transfusion and absolute reticulocyte count At the 16th week, 85% of the patients in the pegcetacoplan group had no blood transfusion, while 15% in the eculizumab group In addition, pegcetacoplan also showed positive results in LDH and fatigue In this study, the safety of pegcetacopolan was comparable with that of eculizumab The incidence of serious adverse events was 17.1% and 15.4% respectively There was no meningitis rate or death report in both groups During the 16 week randomized control period, the most common adverse reactions in the pegcetacoplan group and the eculizumab group were injection site reaction (36.6% vs 2.6%), diarrhea (22.0% vs 0%), headache (7.3% vs 20.5%), fatigue (4.9% vs 15.4%) Another common side effect was hemolysis (9.8% vs 23.1%), which resulted in discontinuation of pegcetacopolan in 3 cases All patients (77 / 80) who completed randomized treatment in the two groups have entered the 32 week open label pegcetacoplan treatment period The detailed results of the study will be presented at a future medical conference Dr Federico Grossi, chief medical officer of apellis, said: "pegcetacoplan is the first and only research therapy that shows superior hemoglobin level to eculizumab We are also pleased to see that 85% of patients treated with pegcetacoplan did not receive blood transfusion We are committed to the development of breakthrough treatment methods, these results show that pegcetacoplan has the potential to change the lives of PNH patients We look forward to meeting with regulators in the first half of this year to discuss next steps " Dr Peter hillmen, Pegasus researcher and professor of Experimental Hematology at the University of Leeds, said: "most of the PNH patients who are currently being treated with eculizumab suffer from persistent anemia The results of Pegasus study show that pegcetacoplan may become a new nursing standard for PNH patients " Pegcetacopolan is a kind of research and targeted C3 inhibitor, which aims to regulate the over activation of complement, which is the cause of many serious diseases Pegcetacopolan is a synthetic cyclic peptide that binds to a polyethylene glycol polymer and specifically to C3 and C3b At present, pegcetacoplan is being developed to treat a variety of diseases, including PNH, map like atrophy (GA) and C3 glomerulopathy In the United States, the FDA has granted pegcetacoplan a fast track qualification for PNH and GA treatment Soliris is a drug sold by alexion, a pioneering complement inhibitor that works by inhibiting C5 protein in the terminal part of the complement cascade reaction Complement cascade reaction is a part of immune system, and its uncontrolled activation plays an important role in a variety of serious rare diseases and super rare diseases Soliris was first approved for marketing in 2007, before which it has been approved for four kinds of super rare diseases: PNH, atypical hemolytic uremic syndrome (aHUS), general myasthenia gravis (GMG) with positive anti AChR antibody, and nmosd with positive anti AQP4 antibody Soliris is one of the world's best-selling orphanages, with sales of $3.563 billion in 2018 Alexion is also developing an upgraded version of soliris product ultomiris, which was approved by FDA for PNH indications in December 2018 In October 2019, ultomiris was approved by FDA as a new indication for the treatment of children and adults with aHUS Ultomiris is the first and only long-acting C5 complement inhibitor given every 8 weeks In the phase III clinical study of PNH treatment, ultomiris infusion every 2 months (8 weeks) and soliris infusion every 2 weeks achieved non inferiority in all 11 endpoints The industry predicts that ultomiris will become a new standard for clinical treatment of PNH Evaluatepharma, a pharmaceutical market research firm, predicts that ultomiris' sales will reach $3.43 billion in 2024 At present, alexion is actively promoting the market penetration of ultomiris, and is also actively developing other indications of ultomiris (including aHUS, GMG) and the development of hypodermic injection type ultomiris Original source: apex reports positive top-line results from phase 3 head-to-head study of pegcetacopolan (APL-2) compared to economicab in patients with paroxysmal nocturnal hemoglobinuria (PNH)