Pooled Clinical Trial Data Suggests Antidrug Antibody Testing for Alglucosidase Alfa-Exposed Patients With Pompe Disease


Investigators concluded that those receiving avalglucosidase alfa should be tested for antidrug antibodies by physicians who treat Pompe disease and monitor antidrug antibody, according to a recent Sanofi investigation.

Priya S. Kishnani, MD, MBBS, C.L., Chen Family Distinguished Professor of Pediatrics at Duke Health

Priya S. Kishnani, MD, MBBS, C.L.

Findings from a recent pooled analysis of clinical trial data of 58 adults and 20 children with Pompe disease showed that avalglucosidase alfa’s (Nexviazyme; Sanofi) immunologic profile improved in comparison with alglucosidase alfa and indicated trends for lower antibody titers. Ultimately, the data suggest that antidrug antibody testing should occur in this patient group.1

Presented as an abstract at the 2022 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting, held September 21-24, in Nashville, Tennessee, by Priya S. Kishnani, MD, MBBS, C.L., Chen Family Distinguished Professor of Pediatrics at Duke Health, and colleagues, the study showed that of 58 adults, 43 (74%) developed antibodies by extension start, and 23 participants (53%) had titers boosted by a roughly 4-fold amount.

There was also the indication of lower catalytic-neutralizing antibody incidence gathered from the COMET trial (NCT02782741) data during the primary analysis period. The clinical trial data for the pooled analysis came from the NEO-EXT (NCT02032524) and NEO1 extension (NCT01898364) studies, and extension data from COMET (NCT02782741) and Mini-COMET (NCT03019406) studies.1

Recently, avalglucosidase alfa received marketing authorization in several countries for infantile- and/or late-onset Pompe disease including the United States, being approved in August 2021. In relation to the approval of the treatment, a pool analysis of clinical data was conducted on examining avalglucosidase alfa antidrug antibody responses in alglucosidase alfatreatment-experienced participants receiving avalglucosidase alfa.

Of the total number of adults, 9 (16%) developed treatment induced antidrug antibodies, producing peak titers of 100 to 1600arbitrary units (AU)/mL. Seven antidrug antibody positive adults (12%) developed only the catalytic-neutralizing antibody, while9 antidrug antibody positive adults (16%) had an uptake of the only the catalytic-neutralizing antibody. Overall, 3 participants (5%) had both antibodies and 39 participants (67%) had neither.

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As for the children in the study, 3 (15%) had antibodies from the beginning of the investigation. Seven (35%) of the children who were seronegative at the start of the trial developed treatment-induced antidrug antibody titers of 100 to 6400 AU/mL while none reached 12,800AU/mL or greater. In particular, 1 child had a transient uptake of the catalytic-neutralizing antibody.

Overall, Kishnani and colleagues concluded that there were no immunogenicity-related concerns observed in the participants when switching from alglucosidase alfa to avalglucosidase alfa across the trials. “Physicians who treat Pompedisease and monitor [antidrug antibodies] are advised to test specifically for anti-[avalglucosidase alfa] antibodies in patients receiving [avalglucosidase alfa],” they wrote.

Previously, in a conversation with NeurologyLive®, Kishnani spoke about the COMET study on avalglucosidase alfa and treating patients with late-onset Pompe disease, data which she presented at the 2021 at the WORLD Symposium. The presentation covered how the enzyme replacement agent compared with another of Sanofi’s products, alglucosidase alfa (Lumizyme), and met the primary end point of noninferiority in respiratory function.2

Kishnani said to NeurologyLive® at the time that, “the data shows clinically meaningful improvements in respiratory muscle function, mobility, muscle strength and function, and disease-specific biomarkers (urine Hex4), in patients with LOPD, translating into improved health-related quality of life in both adult and pediatric patients.” She added that they saw the sustained benefit of treatment with avalglucosidase alfa in patients with LOPD who have participated in the NEO-EXT study for up to 6 years.

“Data on participant-level analyses from the Mini-COMET study confirmed previous group-level results, showing that avalglucosidase alfa has the ability to improve or better stabilize symptoms of IOPD compared to alglucosidase alfa, with additional benefits from the higher 40 mg/kg dose of avalglucosidase alfa. Avalglucosidase alfa was also shown to improve ptosis in long-term LOPD survivors who have been treated with alglucosidase alfa,” Kishnanisaid.

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1. Kishnani P, Richards S, Al-Hassnan Z, et al.Avalgucosidase Alfa Immunogenicity in Alglucosidase Alfa-Experienced Participants with Pompe Disease: Pooled Analysis of Clinical Trial Data.Presented at: AANEM 2022; September 21-24; Nashville, TN. Abstract 107.
2. Krishnani P, Attarian S, Borges JL, et al. Efficacy and Safety Results of the Avalglucosidase alfa Phase 3 COMET Trial. Presented at: WorldSymposium; February 12, 2021; Virtual. Poster 121.
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