New drugs for rare diseases! Sanofi Pompeii II Enzyme Replacement Therapy avalglucosidase alfa head-to-head III clinical success!

, June 18, 2020 /

BIOON/Sanofi has announced positive results from avaluidase alfa (neoGAA) head-to-head III COMET studyThe data showed a clinically significant improvement in the key manifestations of late-hair Pompeii disease (LOPD) (respiratory disorders and decreased mobility)The study also reached the main end point: in LOPD patients, avalglucosidase alfa showed non-poor effects in improving respiratory function compared to the standard care drug Lumizyme (alglucosidase alfa, aglulyglyglynesease alpha)these data will form the basis for a global regulatory application expected in the second half of this yearPreviously, the U.SFDAhas awarded avalglucosidase alfa for the treatment of Pompeii's breakthrough drug (BTD) and fast-track (FTD)COMET is a random, double-blind, head-to-head PHASE III study that enrolled 100 previously untreated LOPD children and adult patients in 56 centers in 20 countriesIn the study, these patients were randomly divided into two groups and received intravenous drops of 20 mg/kg of avalglucosidase alfa, or 20 mg/kg aglucosidease alpha (standard care) every 2 weeks for 49 weeksAfter 49 weeks, patients receiving standard care were transferred to open label treatment using avalglucosidase alfa at 20 mg/kgThe main endpoint of the study was the predicted percentage of forced lung capacity (FVC) in the upright position to assess changes in respiratory muscle functiondata show that compared to standard care drugs (95% CI, -0.13/4.99), the percentage of FVC predicted by patients receiving avalglucosidase alfa increased by 2.4 percentage points, and the numerical improvement in respiratory function exceeded the non-disadvantaged indicators of the study design (p.0074)the primary endpoint also measured superiority, showing that the advantage of avalglucosidase alfa was not statistically significant (p.0626)Therefore, according to the hierarchical system of the research programme, no formal statistical testise is carried out for all secondary endpointsa key secondary endpoint of the study was to measure mobility with a six-minute walking test (6MWT)Patients treated with avalglucosidase alfa walked 30 metres more than those treated with standard care medication (95% CI: 1.33-58.69)Other secondary endpoints assessed respiratory muscle strength, motor function and quality of lifein addition, a pre-specified preliminary analysis assessed the predicted FVC percentage and 6MWT in patients who switched from standard care drugs to avalglucosidase alfa treatment during the study open label expansion period at week 49Due to sequential entry, at the preliminary analysis point in time: at 97 weeks, 20 of the 49 conversion patients had predictive FVC percentage data and 21 patients had 6MWT dataAmong these conversion patients, avalglucosidase alfa showed an improvement of FVC (95% CI:-1.95/2.25) by 0.15 points and 6MWT (95% CI:-3.87/50.51) by 23.32 mavalglucosidase alfa is as safe as standard care drugsDuring the 49-week double-blind period, 44 patients in the avalglucosidase alfa group and 45 patients in the standard care group developed adverse events (AE)Avalglucosidase alfa group 6 cases of severe adverse events, standard treatment group 7 casesThere were fewer patients (8 cases, including 1 potential treatment-related SAE) in the avalidase alfa group than in the standard care group (12 cases, including 3 potential treatment-related SAEs)in the standard care group, 4 patients developed adverse events that led to the discontinued drug use, and 1 patient died of acutemyocardial infarctionadverse events (not related to treatment)In the avalglucosidase alfa group, no patients stopped taking drugs or diedThe proportion of patients in the avalglucosidase alfa group (25.5 per cent) who showed at least one programme-defined infusion-related response was lower than in the standard care group (32.7 per cent)Immunogenicity data are currently being analysed and will be published at a futureof the MedicalConference Dr Jordi Diaz-Manera, professor of neuromuscular disease, translational medicine and genetic
s at the John Walton Centre for Muscular Dystrophy research at the John Walton Centre for Muscular Dystrophy, uk, said: "Pompeii gradually worsens muscles and debilitates them Importantly, potential new treatments allow patients to make clinical improvements in a variety of measurements of breathing and motor function The results of the Part III COMET study are very encouraging and add to the growing body of clinical evidence that aglucosvalidase alfa has the potential to provide new therapeutic options in addressing the characteristic symptoms of the disease John Reed, M.D., head of global research and development at Sanofi, said: "We are pleased that avalglucosidase alfa has shown clinical lying improvements in respiratory function and activity, as measured by the accepted standard prognosis for Pompeii These results underscore our ambition to use avalglucosidase alfa as the new standard for the treatment of Pompeii disease "
Pompeii pathway (pictured: foodnhealth.org) Pompeii is caused by genetic defects or a disorder of the lysozyme acid alpha-glucose (GAA) function, resulting in the accumulation of muscle (including near-end muscles and shin muscles) glycogen, which eventually leads to aggressive and irreversible muscle damage The rare disease affects about 50,000 people worldwide, from infancy to late adulthood, and can manifest itself at any age Pompeii is usually classified as late-haired Pompeii disease (LOPD) or infancy Pompeii disease (IOPD) PATIENTS WITH LOPD USUALLY OCCUR BETWEEN THE FIRST YEAR OF LIFE AND LATE ADULTHOOD The characteristic symptoms of LOPD are impaired respiratory function and skeletal muscle weakness, which often leads to impaired motor ability Patients usually need a wheelchair to help with mobility, or mechanical ventilation may be required to help with breathing Respiratory failure is the most common cause of death in Pompeii patients Pompeii is classified as IOPD and symptoms begin before the age of one In addition to skeletal muscle weakness, heart function is also generally affected Pompeii Enzyme Replacement Therapy (ERT) is designed to introduce enzymes (GAA) into lysosomes in muscle cells to replace missing or missing GAA, an enzyme necessary to prevent the accumulation of glycogen in muscles The avaloglucosidase alfa is a Pompeii disease ERT in the study designed to improve the transfer of enzymes to muscle cells, especially to skeletal muscles Compared to the standard care drug glucosalidase alpha, the content of glutalytic-6-phosphate (M6P) in avaloglucosidase alfa increased by about 15 times, with the aim of helping to increase the absorption of cytoenzymes and the removal of target glycogens The clinical relevance of this difference has not been confirmed Lumizyme (aglucolycoside enzyme alpha) is the first generation erT developed by Sanofi and has been approved for the treatment of Pompeii disease Avaloglucosidase alfa is the second generation of algluidase alpha (alglucosidase alfa) ERT, specifically designed to enhance receptor targeting and enzyme absorption by greater affinity on muscle cells to enhance glycogen removal and improve clinical efficacy of aglucosidease alpha In preclinical studies, avaloglucosidase alfa showed 5 times the efficacy of alpha in the reduction of tissue glycogen In the mouse model of Pompeii, avaloglucosidase alfa showed similar levels of lower substrates at a fifth dose of aglucosidease alpha (biovalleybioon.com) original source: Sanofi's ssenzyme's saure enzyme stherapy show clinically seiny sein disain disaindeddi a.e.a
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