A three-month delay proved to be of no concern for Nexviazyme (avalglucosidase alfa-ngpt, neoGAA), Sanofi SA’s long-term enzyme replacement therapy (ERT), which gained FDA approval for intravenous infusion to treat patients 1 and older with late-onset Pompe disease.

Designed to be administered as a monotherapy ERT every two weeks, Nexviazyme is expected to be available in the coming weeks, according to Paris-based Sanofi. The drug’s recommended dose is based on body weight – at 20 mg/kg for patients who weigh 30 kg or less or at 40 mg/kg for patients weighing over 30 kg.

Sanofi has said it will price Nexviazyme the same as the only other FDA-approved therapy, alglucosidase alfa, also sold by Sanofi and branded Lumizyme. The 2020 annual cost per patient for Lumizyme treatment was estimated to be about $630,000.

The BLA was accepted in November 2020, with the FDA granting a priority review, though the PDUFA date was delayed for three months, from May 18 to Aug. 18. Included in the application were data from the pivotal phase III Comet trial, which tested avalglucosidase alfa against the current standard of care, Lumizyme, in patients with late-onset Pompe disease (LOPD). The primary endpoint, which evaluated the change in respiratory muscle function using percent-predicted forced vital capacity (FVC) in the upright position, showed patients receiving Nexviazyme had a 2.4-point greater improvement vs. Lumizyme, surpassing the noninferiority endpoint (p=0.0074) but falling short of statistical superiority (p=0.0626). A secondary endpoint, measuring mobility via the six-minute walk test, showed those given Nexviazyme walked 30 meters farther than patients treated with standard of care.

Additional safety data from the phase II study known as mini-Comet, which enrolled patients with infantile-onset Pompe disease (IOPD), also were included in the BLA.

In addition to priority review, Nexviazyme was given FDA fast track, orphan and breakthrough therapy designations.

Pompe disease, which is estimated to affect about 50,000 people worldwide, is caused by a genetic deficiency or dysfunction of lysosomal enzyme acid alpha-glucosidase (GAA), an enzyme used by heart and muscle cells to convert glycogen into energy. Without a properly functioning enzyme, the build-up of glycogen results in muscle weakness and impaired respiratory function. Disease progression varies among patients, and Pompe is typically classified as either IOPD or LOPD, the latter describing symptoms that present any time after the first year of life to late adulthood.

For the last decade, the standard of care has been Lumizyme, an ERT first approved by the FDA in 2010 for LOPD patients and expanded to include Pompe patients under the age of 8 in 2014. While it works like Lumizyme, Nexviazyme is designed to improve the delivery of the GAA enzyme. It is estimated to produce a roughly 15-fold increase in mannose-6-phosphate (M6P) content vs. Lumizyme. Sanofi has noted that M6P is a receptor that plays a key role in the transport of GAA.

Going into the PDUFA date, concerns largely centered on whether the noninferiority data from Comet would be sufficient for approval.

Also pending review is AT-GAA (cipaglucosidase alfa/miglustat), a combination product from Amicus Therapeutics Inc. that combines a synthetic version of GAA with an enzyme stabilizer. Data unveiled in February 2021 from the phase III Propel trial in patients with late-onset disease showed superiority over Lumizyme in FVC, but missed the primary endpoint using the six-minute walk test. Citing the totality of the data – as well as the fact that Lumizyme’s approval came on the back of FVC data – Amicus went ahead and completed its rolling BLA. An FDA decision is expected around Oct. 1, 2021.

In June, Amicus reported that the U.K.’s MHRA granted early access to AT-GAA for patients who have received standard of care with Lumizyme for at least two years.

Given the designs and patients populations, it’s not practical to compare the data from Sanofi’s Comet study and Amicus’ Propel trial, though analysts are largely expecting both products to eventually replace Lumizyme for treating LOPD patients.

Nexviazyme also is under review in Europe, with a decision expected in the second half of 2021. The U.K.’s MHRA has granted the product promising innovative medicine, or Prime, designation.

While the ERTs battle it out in the market, other approaches are advancing in development, including a gene therapy from Roche Holding AG’s Spark Therapeutics. SPK-3006, a liver-directed adeno-associated viral vector, is in a phase I/II trial in patients with late-onset disease. Provention Bio Inc. is trying the bispecific antibody approach, having recently reported promising data from a preclinical proof-of-concept study in a mouse model testing PRV-3279, which targets B-cell surface proteins CD32B and CD79B.