Neuro News Roundup: International Pompe Day


In recognition of International Pompe Day, held on April 15, 2023, get caught up on some of the latest news in Pompe disease as the NeurologyLive® team shares some of our data updates.

Pompe disease, a rare inherited lysosomal disease, manifests in 3 variations. One is classic infantile-onset disease, which appears within a few months of birth, with nonclassic infantile-onset appearing at about 1 year. Late-onset Pompe appears during adolescence or adulthood.

For International Pompe Day — April 15, 2023 —the team has culminated some of the biggest pieces of news to offer updates on new developments in the literature on Pompe disease to spread awareness on the prevention and treatment of the rare neuromuscular disease.

Click here for more coverage of the latest news in the neuromuscular field from NeurologyLive®.

Latest Literature

AT845 Shows Promising Efficacy for Late-Onset Pompe Disease in Phase 1/2 Trial

Recent interim data from the phase 1/2 FORTIS clinical trial (NCT04174105) assessing Astellas Pharma’s AT845 displayed promising efficacy for the treatment of late-onset Pompe disease (LOPD).1,2 AT845, an investigational adeno-associated virus (AAV) vector-based gene replacement therapy, is intended to deliver a functional copy of the acid alpha-glucosidase (GAA) gene with a muscle-specific promotor via an AAV8 vector with tropism to muscle tissue.

Among the 4 patients treated with AT845 in the FORTIS trial so far, 3 have ceased treatment with their prior standard of care treatment, enzyme replacement therapy (ERT). Patient 1, a 52-year-old male patient with 68 weeks of follow-up, withdrew from ERT at 17 weeks post-treatment with AT845; Patient 3, a 66-year-old male patient with 54 weeks of follow-up, withdrew from ERT at 10 weeks post-treatment; and Patient 9, a 49-year-old female patient with 43 weeks of follow-up, withdrew from ERT at 24 weeks. Patient 2, a 48-year-old female patient with 78 weeks of follow-up, has not withdrawn from ERT. Patient 2 and Patient 1 received a dose of 3.0x1013 vg/kg of AT845 and Patient 3 and Patient 9 received a dose of 6.0x1013 vg/kg of AT845.

All patients showed stable forced vital capacity over time post treatment of AT845, including after ERT withdrawal. Similarly, patients’ performance on the 6-Minute Walk Test remained stable over time following treatment, including after ERT withdrawal. On the Patient-Reported Outcomes Measurement Information System (PROMIS) Item Bank v1.0 Fatigue-Short Form 8a, Patients 2, 1, and 3 expereinced stable scores after treatment, while Patient 9’s score trended towards improvement from baseline. In addition, on PROMIS scales for ability to participate in social roles and activities, sleep disturbance, and physical function, the 4 patients also displayed stability over time. Notably, patients also had stability on measures of ability to perform daily activities and social participation on the Rasch-built Pompe-specific Activity instrument scale following treatment with AT845.

AT845 Shows Promising Efficacy for Late-Onset Pompe Disease in Phase 1/2 Trial

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

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. Of the 58 adults included, 43 (74%) developed antibodies by extension start, and 23 participants (53%) had titers boosted by a roughly 4-fold amount.3

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.

Of the total number of adults, 9 (16%) developed treatment induced antidrug antibodies, producing peak titers of 100 to 1600 arbitrary units (AU)/mL. Seven antidrug antibody positive adults (12%) developed only the catalytic-neutralizing antibody, while 9 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.

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

Cipaglucosidase Alfa/Miglustat Shows Beneficial Treatment Effects for Patients With Late-onset Pompe Disease

Over the course of 36 months, cipaglucosidase alfa/miglustat, an investigational treatment from Amicus Pharma for late-onset Pompe disease (LOPD) displayed a safety profile similar to approved enzyme replacement therapy (ERT) and was associated with reduced creatine kinase and urine Hex4.4 Researchers highlighted cipaglucosidase alfa/miglustat, also known as AT-GAA, as a beneficial 2-component therapy for Pompe disease.

ATB200-02 enrolled 3 cohorts of ambulatory patients based on ERT experience: those with 2 to 6 years (n=11; aged 18-65 years) or with 7 or more years (n=6; aged 18-75 years) were both administered 20 mg/kg alglucosidase alfa biweekly, and those who were ERT-naïve (n=6; aged 18-65 years) who were given doses of 20 mg/kg IV cipaglucosidase alfa/260 mg miglustat orally biweekly.

At 6, 12, 24, and 36 months, integrated analyses of the ERT-experienced cohorts showed improvementsin 6-minute walk distance from baseline of 23.1 m (SD, 44.75; n = 16), 33.5 m (SD, 49.62; n = 16), 21.3 m (SD, 60.90; n = 10), and 47.8 m (SD, 53.80; n = 8), respectively. Comparatively, the ERT-naïve cohort reported improvements of 36.7 m (SD, 29.08; n = 6) at 6 months, 57.0 m (29.96; n = 6) at 12 months, 60.7 m (SD, 36.52; n = 5) at 24 months, and 43.5 m (45.19; n = 5) at 36 months.

Cipaglucosidase Alfa/Miglustat Shows Beneficial Treatment Effects for Patients With Late-onset Pompe Disease
1. Diaz-Manera J, Mozaffar T, Longo N, et al. AT845 gene replacement therapy for late onset Pompe disease: An update on safety and preliminary efficacy data from FORTIS, a phase I/II open-label clinical study. Presented at WORLDSymposium 2023, held February 22-26, in Orlando, Florida. Abstract #95
2. Astellas announces update on preliminary safety and efficacy data from FORTIS study of investigational AT845 in adults with late-onset Pompe disease. News release. Astellas Pharma Inc. February 22, 2023. Accessed February 24, 2023.
3. 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.
4. Byrne B, Schoser B, Kishnani, et al. Long-term Follow Up of CipaglucosidaseAlfa/Miglustat in Ambulatory Patients with Late-Onset PompeDisease: an open-label phase I/II study (ATB200-02). Presented at: AANEM 2022; September 21-24; Nashville, TN. Abstract104.
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