Results from the COMET study were recently reported showing neoGAA (avalglucosidase alfa), the newer enzyme replacement therapy (ERT) currently in development, to be as effective as the currently approved ERT, Myozyme (alglucosidase alfa), in persons with late-onset Pompe disease.

The developer of neoGAA, Sanofi, reported their phase 3 COMET trial testing neoGAA in persons with late-onset Pompe disease met its primary endpoint which was to show this newer ERT was not worse than the current standard of care, Myozyme (i.e., a non-inferiority clinical trial).

Interestingly, neoGAA may also be slightly better than Myozyme. In the trial, the primary endpoint was the change in respiratory muscle function using percent-predicted forced vital capacity (FVC) in the upright position. Patients treated with neoGAA had a 2.4-point greater improvement in percent-predicted FVC compared to patients treated with Myozyme.

While it did show a statistically significant non-inferiority comparison (P < .05), a second primary endpoint was to determine if the newer treatment was statistically superior to the older treatment. In that regard, the superiority comparison was not statistically significant (P = .06).

The secondary endpoint, 6MWT, indicates improvement over Myozyme, with patients walking an average of 30m further over six minutes.

A full list of the outcome measures is in the table below:

Trial Endpoints neoGAA*

N = 51


N = 49

Least Square Mean Difference (95%CI)

N = 100

Primary Endpoint
FVC (% predicted) 2.89 (0.88) 0.46 (0.93) 2.43 (-0.13, 4.99)
Secondary Endpoints
6MWT 32.21 (9.93) 2.19 (10.40) 30.01 (1.33, 58.69)
Maximum Inspiratory Pressure (% predicted) -0.29 (3.84) -2.87 (4.04) 2.58 (-8.54, 13.71)
Maximum Expiratory Pressure (% predicted) 2.39 (4.00) 5.00 (4.20) -2.61 (-14.22, 9.00)
Hand-held dynamometry Composite Score 260.69 (46.07) 153.72 (48.54) 106.97 (-26.56, 240.50)
Quick Motor Function Test Total Score 3.98 (0.63) 1.89 (0.69) 2.08 (0.22, 3.95)
Health-related survey on quality of life (SF-12)
• Physical Component Summary Score 2.37 (0.99) 1.60 (1.07) 0.77 (-2.13, 3.67)
• Mental Component Summary Score 2.88 (1.22) 0.76 (1.32) 2.12 (-1.46, 5.69)

* Least square mean changes (standard error) from baseline at week 49

Looking at the safety profile, the data so far shows neoGAA to be comparable to Myozyme. Over the 49-week study, 44 patients in the neoGAA group and 45 patients in the Myozyme group experienced an adverse event(s). There were 6 patients with severe AEs in the neoGAA group and 7 patients in the Myozyme group.

neoGAA is an investigational ERT for Pompe disease designed to improve the delivery of the enzyme to muscles. In addition to being tested in late-onset Pompe disease, the drug is also being investigated infantile-onset Pompe disease. Both neoGAA and Myozyme are administered intravenously every 2 weeks (20 mg/kg).

To learn more about these clinical studies, visit


Tagged: clinical trials, ERT