New data demonstrate clinical safety, benefit and durability of Nexviazyme (avalglucosidase alfa) across a wide-range of Pompe disease patient groups

These findings, from the Phase II Mini-COMET study long-term extension, will be featured at the 20th annual WORLDSymposium, along with debut data (positive safety results) from the Phase III Baby-COMET trial, the first study of avalglucosidase alfa in never-before-treated patients with IOPD, and the first study in over 20 years of any treatment in naïve IOPD patients.

Ptosis (drooping eyelid) impacts ~50% of IOPD patients, potentially causing vision loss and decreased quality of life. Nexviazyme is a monotherapy approved in the US and other markets for juvenile and adult patients with LOPD. It is also approved for IOPD in certain markets outside of the US.

Also featured at WORLDSymposium 2024 are presentations of key findings surrounding avalglucosidase alfa use in late-onset Pompe disease (LOPD). This includes positive long-term results from the NEO-EXT study up to eight years, as well as real-world findings from the international, voluntary Pompe Registry sponsored by Sanofi, of people who switched to avalglucosidase alfa from prior treatment with long-time standard of care, alglucosidase alfa..

In the comparative COMET study, fewer LOPD patients in the avalglucosidase alfa group reported at least 1 IAR (13/51 [25.5%]) in comparison to the alglucosidase alfa group (16/49 [32.7%]). The most frequently reported treatment-emergent IARs ( greater than 2 patients) in the avalglucosidase alfa group were pruritus (7.8%) and urticaria (5.9%). Additionally, hypersensitivity reactions were observed in 12 (24%) participants in the avalglucosidase alfa group and 15 (31%) in the Myozyme group. The majority of IARs and hypersensitivity reactions were mild or moderate.

Nexviazyme Data in Infantile-Onset Pompe Disease : Ptosis findings from Mini-COMET: The Phase II Mini-COMET study evaluated the efficacy and safety of avalglucosidase alfa in patients under 18 years of age with IOPD who previously received alglucosidase alfa for six or more months and showed either clinical decline (Cohorts 1 and 2) or suboptimal response (Cohort 3). In the 25-week primary analysis period, Cohort 1 received 20 mg/kg of avalglucosidase alfa every two weeks (n=6), Cohort 2 received 40 mg/kg of avalglucosidase alfa every two weeks (n=5), and Cohort 3 was randomized to either avalglucosidase alfa 40 mg/kg every two weeks (3a; n=5) or alglucosidase alfa at their pre-enrollment stable dose (3b; within a range of 20mg/kg every two weeks to 40mg/kg weekly [n=6]).

All 22 participants entered an extension period to receive up to 40 mg/kg of avalglucosidase alfa every two weeks for up to nearly three years (Week 145). At predefined time points, ptosis, a secondary endpoint, was evaluated by an ophthalmologist through standard eyelid measurements. After nearly three years (Week 145), patients who received the higher dose of avalglucosidase alfa every two weeks (40 mg/kg; Cohorts 2 and 3a) had clinically meaningful improvements in ptosis compared to those on an initial bi-weekly 20 mg/kg dose of avalglucosidase alfa (Cohort 1) or those initially receiving alglucosidase alfa for the first 25 weeks (Cohort 3b).

Safety findings from Baby-COMET: Safety results from the Phase III Baby-COMET trial, the first study evaluating the safety and efficacy of avalglucosidase alfa for treatment-naive patients with IOPD (?6 months of age at enrollment) (n=11), showed no unexpected safety issues at data cut-off. 9/11 (82%) participants had a total of 59 treatment-emergent adverse events (TEAEs): none had severe TEAEs, four patients had a total of six serious TEAEs (two of COVID-19, and one each of bronchitis, urinary tract infection, hyperkalemia, febrile convulsion). No deaths were reported.

Nexviazyme Data in Late-Onset Pompe Disease : Real-world findings in patients switching from prior therapy: Real-world evidence from the international, voluntary Pompe Registry sponsored by Sanofi aimed to characterize the clinical characteristics of patients with LOPD who switched from long-time standard of care, alglucosidase alfa, to avalglucosidase alfa treatment. The analysis followed 161 patients with LOPD who had received avalglucosidase alfa for up to one-year post-switch, with 60.2% having received alglucosidase alfa for greater than 5 years pre-switch. Results showed that patients who switched to avalglucosidase alfa had stabilized respiratory function and mobility, as measured by upright forced vital capacity and 6-minute walk test, respectively. Patients also had improvements in disease-associated biomarkers after switching to avalglucosidase alfa, as measured by urinary glucose tetrasaccharide/hexose tetrasaccharide levels as well as creatinine kinase (CK), a measure of muscle dysfunction.

Long-term follow-up data from NEO-EXT: Eight-year follow-up results from the NEO-EXT trial, a Phase II/III study investigating the long-term safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of avalglucosidase alfa in patients with LOPD who participated in the Phase 1 NEO1 trial, were reported. Muscle quantitative magnetic resonance imaging (qMRI) showed a trend of stabilization over time, corroborating the clinical stability demonstrated through retained lung capacity and physical endurance. Participants in the NEO-1 trial were treatment-naïve (n=10) or had received alglucosidase alfa for greater than 9 months (Switch, n=14) at baseline and received avalglucosidase alfa (5, 10, or 20 mg/kg/every other week [qow]) for six months. Nineteen participants entered NEO-EXT receiving their NEO1 avalglucosidase alfa dose until 2016; thereafter all received avalglucosidase alfa 20 mg/kg/qow.