Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial

Díaz‐Manera, Jordi; Kishnani, Priya S.; Kushlaf, Hani; Ladha, Shafeeq; Mozaffar, Tahseen; Straub, Volker; Toscano, Antonio; Ploeg, Ans T. van der; Berger, Kenneth I.; Clemens, Paula R.; Chien, Yin‐Hsiu; Day, John W.; Иллариошкин, С.Н.; Roberts, Mark; Attarian, Shahram; Borges, João Lindolfo Cunha; Bouhour, Francoise; Choi, Young Chul; Erdem-Özdamar, Sevim; Göker-Alpan, Özlem; Kostera‐Pruszczyk, Anna; Haack, Kristina An; Hug, Christopher; Huynh-Ba, Olivier; Johnson, Judith; Thibault, Nathan; Zhou, Tianyue; Dimachkie, Mazen M.; Schöser, Benedikt; Béhin, Anthony; Boentert, Matthias; Carvalho, Gérson; Chahin, Nizar; Charrow, Joel; Deegan, Patrick; Tekçe, Hacer Durmuş; Duval, Fanny; Genge, Angela; Gutmann, Ludwig; Henderson, Robert D.; Hennermann, Julia B.; Hiwot, Tarekegn; Hughes, Derralynn; Karaa, Amel; Karam, Chafic; Kautzky‐Willer, Alexandra; Komaki, Hirofumi; Laforêt, Pascal; Longo, Nicola; Malinová, Věra; Maré, Ricardo; Maxit, Clarisa; Mengel, Eugen; Moggio, Maurizio; Molnár, Mária Judit; Mongini, Tiziana; Nadaj‐Pakleza, Aleksandra; Osorio, A. Nascimento; Noury, Jean-Baptiste; Oliveira, Acary Souza Bullé; Parman, Yeşim; Peña, Loren; Remiche, Gauthier; Sciacco, Monica; Shieh, Perry B.; Smith, Cathy; Stulnig, Thomas; Taithe, F.; Tard, Céline; Tarnopolsky, Mark A.; Vorgerd, Matthias; Whitley, Chester B.; Young, Peter; Alonso‐Pérez, Jorge; Altemus, Patricia; Aubé-Nathier, Anne-Catherine; Avelar, Jennifer; Bailey, Carrie; Bekircan-Kurt, Can Ebru; Billy, Jenny; Boschi, Silvia Regina Matos da Silva; Brown, Kathryn E.; García, Laura Carrera; Chase, Lauren; Cirne, Hamilton; Danjoux, Loïc; Davion, Jean‐Baptiste; DeArmey, Stephanie; Fedotova, E. Yu.; Gandolfo, Eve; Grosz, Zoltán; Guellec, Dewi; Guettsches, Anne-Katrin; Guglieri, Michela; Hatcher, Erin; Helms, Sina; Hufgard-Leitner, Miriam; Klyushnikov, Sergey A.; Langton, Jacqui; Linková, Lenka; Mavroudakis, Nicolas; Mazurová, Stella; Mori, Mitsuo; Müller-Miny, Louisa; Musumeci, Olimpia; Nance, Christopher; Benito, Daniel Natera-de; Neel, Robert W.; Niizawa, Gabriela; Noll, Lauren; Ortega, Erik; Pasnoor, Mamatha; Pautot, Vivien; Potulska‐Chromik, Anna; Pugliese, A.; Questienne, Claire; Lopes, Margarida Ramos; Reyes‐Leiva, David; Riedl, Michaela; Rugiero, Marcelo; Salort‐Campana, Emmanuelle; Souza, Paulo Victor Sgobbi de; Solé, Guilhem; Solera, Luca; Lopes, Suzara Souto; Specht, Sabine; Statland, Jeffrey; Swenson, Andrea; Tan, Chong Yew; Tizon, Sónia; Beek, Nadine A M E van der; Kooten, Harmke A van; Wencel, Marie; Wenninger, Stephan; Zagnoli, Fabien

doi:10.1016/s1474-4422(21)00241-6

Cited by 94 publications

(104 citation statements)

References 34 publications

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“…Avalglucosidase α works by targeting the mannose-6-phosphate receptor resulting in an effective clearance of glycogen build-up in muscle cells (Dhillon 2021a ). Intravenous administration of avalglucosidase α every 2 weeks reduces glycogen accumulation and improves respiratory function (Diaz-Manera et al 2021 ; Kushlaf et al 2021 ). Common side effects include headache, fatigue, diarrhea, nausea, arthralgia, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia, and urticaria.…”

Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition (“first-in-indication”), (2) first drug using a novel molecular mechanism (“first-in-class”), and (3) “next-in-class”, i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indication drugs. By treatment area, the largest group is once again cancer drugs, many of which target specific genetic alterations. Every second drug approved in 2021 targets an orphan disease, half of them being cancers. Small molecules continue to dominate new drug approvals, followed by antibodies and non-antibody biopharmaceuticals. In 2021, the FDA continued to approve drugs without strong evidence of clinical effects, best exemplified by the aducanumab controversy.

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Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Therefore, the decline in the 6MWD cannot be explained by changes in respiratory function in our patient group. However, considering that the parameter that deteriorates is the 6MWD and not muscle strength, it is conceivable that the aspect involved might be functional endurance, corresponding to other recent studies [39]. However, it might also still be possible that the 6MWT is more capable of detecting small declines in distinct functions, taken together (endurance, strength, posture, respiration), that perhaps single outcome measures (FVC alone, and so on) cannot catch.…”

Section: Discussionmentioning

confidence: 85%

Six-Minute Walk Distance Is a Useful Outcome Measure to Detect Motor Decline in Treated Late-Onset Pompe Disease Patients

Claeys

D’Hondt

Fache

et al. 2022

Cells

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Late-onset Pompe disease (LOPD) is a rare, progressive disorder characterized by limb–girdle muscle weakness and/or respiratory insufficiency, caused by acid alpha-glucosidase (GAA) gene mutations and treated with enzyme replacement therapy. We studied isometric muscle strength in eight muscle groups bilaterally using a Biodex® dynamometer, as well as the Medical Research Council sum score (MRC-SS), hand grip strength, 6 min walk distance (6MWD), 10 m walk test (10MWT) and timed up-and-go test (TUG) in 12 adult, ambulatory, treated LOPD patients and 12 age-/gender-matched healthy controls, every 6 months for 2 years. The mean isometric muscle strength showed a significant decline in right and left knee extensors at 12 months in controls (p < 0.014; p < 0.016), at 18 months in patients (p < 0.010; p < 0.007) and controls (only right side, p < 0.030) and at 24 months in both groups (p < 0.035). The mean 6MWD in patients significantly decreased after 24 months, from 451.9 m to 368.1 m (p < 0.003), whereas in controls, the mean 6MWD significantly increased after 6 months (p < 0.045) and 18 months (p < 0.020) (at 24 months p = 0.054). In patients and controls, the MRC-SS, hand grip test, 10MWT and TUG did not show significant changes (p > 0.05). We conclude that the 6MWD is a useful outcome measure to detect motor decline in treated LOPD patients.

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“…The interparticipant and intraparticipant variability of 6MWD is well known; 6MWT has a significant variability across different tests and observers, both in healthy people and in several diseases, including PMM [3,10]. On the other hand, the 6MWT has been used as the main outcome measure in several trials of neuromuscular diseases, including Pompe disease, mucopolysaccharidosis, Duchenne dystrophy and spinal muscular atrophy [6,[11][12][13][14]. Its role in assessing motor performance and exercise intolerance has been evaluated in PMM, and some researchers proposed other measures, like 12MWT or 6MWT slope across minutes as described in RYR related myopathies [10,15].…”

Section: Discussionmentioning

confidence: 99%

Primary mitochondrial myopathy: 12-month follow-up results of an Italian cohort

et al. 2022

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Objectives To assess natural history and 12-month change of a series of scales and functional outcome measures in a cohort of 117 patients with primary mitochondrial myopathy (PMM). Methods Twelve months follow-up data of 117 patients with PMM were collected. We analysed the 6-min walk test (6MWT), timed up-and-go test (× 3) (3TUG), five-times sit-to-stand test (5XSST), timed water swallow test (TWST), and test of masticating and swallowing solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional pain inventory as patient-reported outcome measures. PMM patients were divided into three phenotypic categories: mitochondrial myopathy (MiMy) without extraocular muscles involvement, pure chronic progressive external ophthalmoplegia (PEO) and PEO&MiMy. As 6MWT is recognized to have significant test–retest variability, we calculated MCID (minimal clinically important difference) as one third of baseline 6 min walking distance (6MWD) standard deviation. Results At 12-month follow-up, 3TUG, 5XSST and FSS were stable, while TWST and the perceived pain severity (WHYMPI) worsened. 6MWD significantly increased in the entire cohort, especially in the higher percentiles and in PEO patients, while was substantially stable in the lower percentile (< 408 m) and MiMy patients. This increase in 6MWD was considered not significant, as inferior to MCID (33.3 m). NMDAS total score showed a slight but significant decline at 12 months (0.9 point). The perceived pain severity significantly worsened. Patients with PEO performed better in functional measures than patients with PEO&MiMy or MiMy, and had lower values of NMDAS. Conclusions PMM patients showed a slow global decline valued by NMDAS at 12 months; 6MWT was a more reliable measurement below 408 m, substantially stable at 12 months. PEO patients had better motor performance and lower NMDAS than PEO&MiMy and MiMy also at 12 months of follow-up.

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Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial

Cited by 94 publications

References 34 publications

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Six-Minute Walk Distance Is a Useful Outcome Measure to Detect Motor Decline in Treated Late-Onset Pompe Disease Patients

Primary mitochondrial myopathy: 12-month follow-up results of an Italian cohort

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