"Gradually frozen" new hope! Alexion, the world's first long-acting C5 complement inhibitor ultomiris, has entered phase III clinical treatment of ALS!

January 16, 2020 / BIOON / -- alexion is an American pharmaceutical company dedicated to the research and development of new drugs for rare diseases Recently, the company announced that it plans to launch a key phase III study to evaluate the use of ultomiris (ravulizumab) in the treatment of ALS In the fourth quarter of 2019, the company submitted an investigational new drug application (ind) for the treatment of ALS by ultomiris to the US FDA, and plans to launch the phase III study in this quarter The study, champion-als, is a 50 week, randomized, double-blind, placebo-controlled, multicenter, global phase III study designed to assess the efficacy and safety of ultomiris in a broad population of ALS patients The study will recruit approximately 350 adult patients with sporadic or familial ALS who have developed onset (first exercise symptoms), slow vital capacity (SVC) of at least 65% of the predicted value in the last 36 months, and are not dependent on respiratory support In this study, patients will be randomly assigned in a 2:1 ratio to receive ultomiris or placebo every 8 weeks after the initial load dose, and continue to receive their existing ALS standard care After 50 weeks, all patients will receive ultomiris treatment in a 2-year open label extension period The study will be conducted in about 90 clinical sites in North America, Europe and Asia Pacific The primary end point will be the change in the ALS functional rating scale revised (ALSFRS-R) score from baseline Secondary endpoints included vafs, respiratory capacity, muscle strength, NFL serum concentration, and safety John Orloff, executive vice president and director of research and development of ALXION, said: "in view of the significant demand of ALS patients for new and improved treatment programs, we are committed to promoting this clinical project as soon as possible Based on preclinical data and the important role of complement activation in other neuromuscular diseases, we believe that ultomiris has the potential to inhibit complement mediated injury in ALS patients, which may slow down the progression of the disease We thank the ALS community for participating in the design of this phase III project and look forward to continuing to work closely together as we advance the project " Amyotrophic lateral sclerosis (ALS), commonly known as cryogenics, is an irreversible fatal motor neuron disease, which is characterized by the control of the brain and spinal cord nerve cells (motor neurons) in the muscles of the whole body to undergo sexual degeneration When nerve cells die, the brain can no longer start and control muscle movement, which leads to serious disability, paralysis and eventually death The main symptoms of ALS are progressive muscle weakness and atrophy of limbs and trunk muscles, gradually losing motor function, like being "frozen", so it is commonly known as "gradually frozen people" ALS is a relentless and progressive disease The patient will gradually lose the ability to speak, eat, move and breathe The rate of disease progression among ALS individuals is variable, and natural history usually reflects progressive deterioration over time until death The average life expectancy after the first symptom attack is 2-5 years At present, the approved drugs can only slow down the progress of disease, but als treatment is mainly supportive, palliative and symptom based, and there is no drug that can cure ALS In the United States, France, Germany, Italy, Spain, the United Kingdom and Japan, an estimated 15000-20000 people suffer from ALS There are two different types of ALS: sporadic and familial Sporadic diseases are the most common, accounting for 85% - 90% of cases, and may affect anyone anywhere Familial ALS is a genetic disease type, accounting for 10% - 15% Ultomiris is the first and only approved long-acting C5 complement inhibitor, which works by inhibiting C5 protein in the terminal part of complement cascade reaction Complement cascade reaction is a part of immune system, and its uncontrolled activation plays an important role in severe rare diseases and super rare diseases In the United States, Japan and the European Union, ultomiris has been approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults In the United States, ultomiris was also approved by the FDA in October 2019 as a new indication for the treatment of adult and pediatric patients (≥ 1 month) with atypical hemolytic uremic syndrome (aHUS) to inhibit complement mediated thromboembolic microangiopathy (TMA) In terms of medication, for adult patients, after the initial load dose, ultomiris is infused intravenously every 8 weeks; for pediatric patients whose weight is less than 20 kg, after the initial load dose, ultomiris is infused intravenously every 4 weeks Ultomiris is positioned as an upgraded version of alexion's heavyweight C5 complement inhibitor soliris, which was first approved for marketing in 2007 and has been approved for use in four super rare diseases: PNH, aHUS, generalized myasthenia gravis (GMG) with positive anti acetylcholine receptor antibody, and neuromyelitis pedigree disorder (nmosd) with positive anti AQP4 antibody Soliris is a product that alexion relies heavily on, with more than 80% of its sales coming from the drug Soliris is one of the most expensive drugs in the world (priced at US $500000 / year), and also one of the best-selling orphan drugs in the world In 2018, global sales reached US $3563 million 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 In addition to actively promoting the market penetration of ultomiris, alexion is also actively developing other indications of ultomiris (including aHUS, GMG, etc.) and developing subcutaneous injection type ultomiris At present, soliris and ultomiris also face potential competition from other complement inhibitors in PNH development pipeline Recently, akari C5 complement inhibitor nomacopan (formerly known as coversion, rva576) was successfully used to treat PNH stage III capstone In addition, pegcetacopolan, a C3 complement inhibitor from apellis, beat soliris in the head to head phase III Pegasus study Original source: alexion announcements planned initiation of pivotal phase 3 study of ultomiris ® (ravulizumab) in ALS