Enzyme Replacement Therapy Shows Early Improvement in Pompe Disease


Assessment of forced vital capacity with treatment of enzyme replacement therapy generally showed some initial stability followed by slow progressive decline.

Priya S. Kishnani, MD

Priya S. Kishnani, MD

Data presented at the Muscular Dystrophy Association’s (MDA) Clinical and Scientific Conference, March 15-18, demonstrated that treatment with enzyme replacement therapy (ERT) is associated with initial improvement in motor function followed by a slow decline in patients with late-onset Pompe disease (LOPD).1

The primary end point, 6-minute walk distance (6MWD; measured in meters) measured using the 6-Minute Walk Test (6MWT), was initially improved in patients with LOPD but was maxed out at 2-3 years, and then was followed by a secondary decline.

Lead author Priya S. Kishnani, MD, C.L. and Su Chen Professor of Pediatrics; medical director, YT and Alice Chen Pediatrics Genetics and Genomics Center; and division chief, Medical Genetics, Duke University Medical Center, and colleagues aimed to characterize disease progression in patients with LOPD receiving ERT in a clinical setting using a retrospective chart review.

The median (Q1, Q3) change from baseline in 6MWD was –15.0 meters (–22, 0) at 0.5 years (n = 9), 54.0 meters (–18, 128) at 1.5 years (n = 7), –10.0 meters (–40, 35) at 3 years (n = 9), and –15.5 meters (–60, 24) at longer than 3 years (n = 10) years of treatment follow-up.

A total of 44 patients were included in the efficacy population. At baseline, more than 80% of these patients had difficulty in both respiratory and daily activities. Additionally, 46% required ambulatory support and 61% required ventilator support.

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Kishnani and colleagues also documented 3 patients who previously did not require ambulatory support at baseline, using assistive devices for the 6MWT during follow-up, ranging from visits 3-7. Secondary end points in the study included sitting forced vital capacity (FVC), supine FVC, maximum inspiratory pressure (MEP), and maximum expiratory pressure (MEP). Similar to the 6MWD, sitting FVC showed some initial stability, but was followed by a slow progressive decline when using ERT.

Based on available data, median (Q1, Q3) changes from baseline in sitting FVC percent predicted was –3.0 (–8.0, 3.0) at 0.5 years (n = 17), –1.5 (–5.0, 0.0) meters at 1.5 years (n = 18), –0.5 (–7.0, 5.0) at 3 years (n = 30), and –0.5 (–10.0, 3.9) at longer than 3 years (n = 30). The median follow-up duration was 44 (range, 39-75) months.

Available safety data was reviewed for the whole enrolled population (n = 98). A total of 36 infusion-associated reactions (IARs) were experienced among 18 patients. More specifically, 14 occurred on the day of ERT initiation. The study authors documented that 23 of the IARs were resolved, while 12 remained unresolved and 1 had an unknown outcome.

IARs experienced forced 2 patients to interrupt their treatment with ERT. Anaphylactic reaction to ERT and moderately intense dystonia were found each in 1 patient. Notably, there were no deaths reported in the study.

Currently, the only approved treatment for PD is ERT with alglucosidase alfa (Lumizyme; Sanofi). Kishnani has been a part of the development of Sanofi’s second PD treatment, avalglucosidase alfa, which currently has a prescription drug user fee act (PDUFA) date of May 18, 2021.2

The FDA previously accepted the biologics license application (BLA) for the PD treatment in November 2020, with the basis behind the BLA originating from positive data from both the phase 3 COMET trial (NCT02782741) and the phase 2 mini-COMET trial (NCT03019406). Data from COMET were compiled and presented by Kishnani at the WORLDSymposium 2021 annual conference.

Treatment with the investigational EVT met the primary end point of noninferiority in respiratory function, as measured by FVC predicted, with a substantial improvement from baseline out to week 49 of 2.43% (95% CI, –0.13 to 4.99; P = .0074). When assessed via superiority analysis, the value was .0626.3

For more coverage of MDA 2021, click here.

1. Kishnani PS, Roberts M, Ahmed A, et al. Characterization of response to enzyme replacement therapy in patients with late-onset Pompe disease: a retrospective chart review. Presented at MDA Clinical and Scientific Conferenc 2021; March 15–18.
2. FDA grants priority review for avalglucosidase alfa, a potential new therapy for Pompe disease. News release. Sanofi. November 18, 2020. Accessed March 22, 2021. http://www.news.sanofi.us/2020-11-18-FDA-grants-priority-review-for-avalglucosidase-alfa-a-potential-new-therapy-for-Pompe-disease
3. 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. Poster 121.
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