Nexviazyme shows sustained improvements in respiratory function and mobility in patients with Pompe disease.

This analysis of an open-label, long-term extension of the randomized, double-blind, Phase III COMET trial, was presented at the 18th annual WORLD Symposium. Long-term efficacy and safety outcomes were assessed in patients who had received continuous treatment with Nexviazyme.

In addition, patients treated with Nexviazyme, for at least 48 weeks, after switching from prior treatment with alglucosidase alfa (previously the only available treatment option for Pompe disease and standard of care) were included in the analysis. Over the 97 weeks, there was sustained treatment effect with Nexviazyme along with stabilization of treatment effect in patients switching from alglucosidase alfa in respiratory function (measured by forced vital capacity FVC percent-predicted) and walking distance (measured by the six-minute walk test 6MWT).

The COMET study enrolled 100 previously untreated patients with LOPD across 55 centers in 20 countries. The primary endpoint evaluated the change in FVC percent-predicted in the upright position compared to baseline, and a key secondary endpoint measured mobility with the 6MWT compared to baseline. Patients were randomized to receive either Nexviazyme 20 mg/kg or alglucosidase alfa 20 mg/kg intravenous infusion every two weeks for 49 weeks. During the extension period of COMET, patients who had initially received Nexviazyme continued their treatment, while patients who were previously treated with alglucosidase alfa switched to Nexviazyme 20 mg/kg. Of the 95 participants who entered the extension period, 86 (91%) remained on treatment up to last follow-up.

After nearly two years, changes (LS mean SE) from baseline at week 97 showed: i. Treatment with Nexviazyme in both the primary analysis and extension periods led to a 2.65 (1.05) point improvement in FVC percent-predicted compared to baseline. ii. Patients who were treated with Nexviazyme only during the extension period showed a 0.36 (1.12) point improvement compared to baseline. iii. Patients who were treated with Nexviazyme during both the primary analysis and extension periods experienced an average increase of 18.6 (12.01) meters in walking distance as measured by the 6MWT compared with the distance walked at baseline. Patients who were treated with Nexviazyme only during the extension period showed an average increase of 4.56 (12.44) meters from baseline.

The safety profile was comparable between both treatment arms (those treated with Nexviazyme throughout the study and those switching to treatment with Nexviazyme) during treatment with Nexviazyme. No new safety signals were observed in patients who switched from alglucosidase alfa to Nexviazyme during the extension period. Across both groups, five individuals discontinued treatment during the extension period due to adverse events (AEs) (ocular hyperemia, erythema, urticaria, respiratory distress, acute myocardial infarction, pancreatic adenocarcinoma). Six participants experienced serious treatment-emergent adverse reactions potentially related to therapy.

Phase II Mini-COMET study long-term extension results: Also for presentation at the WORLD Symposium are results from the extension period of the Phase II Mini-COMET trial. This open-label, ascending-dose, three-cohort study evaluated the safety and efficacy of Nexviazyme in patients under 18 years of age with infantile-onset Pompe disease (IOPD), a use that remains under investigation in the United States, who previously received alglucosidase alfa for six or more months and showed either a suboptimal response or a clinical decline. Patients were enrolled into one of three cohorts: (1) 20 mg/kg of Nexviazyme every two weeks (n=6), (2) 40 mg/kg of Nexviazyme every two weeks (n=5), and (3) randomized to Nexviazyme 40 mg/kg every two weeks (n=5) or alglucosidase alfa at their pre-enrollment stable dose (within a range of 20 mg/kg every two weeks to 40 mg/kg weekly n=6). All 22 participants entered an extension period to receive up to 40 mg/kg of Nexviazyme every two weeks.

During the extension period: i. The most commonly reported treatment-emergent AEs were mild to moderate in severity and included rashes (8 participants), falls, pneumonia, pyrexia (7 participants each), headache, upper respiratory tract infections (6 participants each) and vomiting (5 participants). There were no serious or severe treatment-related AEs or deaths. ii. The higher Nexviazyme dose (40 mg/kg every two weeks) had no increased safety risk seen in participants who switched from alglucosidase alfa to Nexviazyme. After two years (at week 97), results showed that patients treated with Nexviazyme showed stable or improved motor function as measured by gross motor function measure (GMFM-88), quick motor function test (QMFT) total percent score, and Pompe-PEDI (Pediatric Evaluation of Disability Index) Functional Skills Scale. Additionally, all participants had a left ventricle mass z-score (LVMZ) score within normal range.

Phase III Baby-COMET trial methodology: The trial design of Baby-COMET, a Phase III, single group, open-label, multinational, multi-center study will also be presented at the congress. Baby-COMET is the first study of Nexviazyme to include participants with IOPD who have never been treated. This study will determine the effects of Nexviazyme, externally compared with alglucosidase alfa, on overall and ventilator-free survival in participants with IOPD 6 months of age at enrollment.