Sanofi notches another Pompe win with FDA blessing for enzyme replacement therapy Nexviazyme

In the realm of rare diseases, Sanofi has added another arrow to its Pompe quiver. 

The FDA cleared Sanofi’s Nexviazyme, also known as avalglucosidase alfa-ngpt, to treat patients ages one and older with late-onset Pompe disease, which damages the muscles over time, the company said Friday. It marks the FDA’s second approved drug for the rare genetic disease, the first of which also belongs to Sanofi.

The company's earlier enzyme replacement therapy (ERT), alglucosidase alfa, was first approved in 2006 as Myozyme (PDF) for infantile-onset disease. In 2010, the same ERT was approved (PDF) as Lumizyme to treat late-onset Pompe in patients ages eight and older, and, in 2014, the FDA expanded (PDF) its label to treat infantile-onset Pompe, too, including in patients younger than eight.

Armed with its new Pompe approval, Sanofi aims to make Nexviazyme available “in the coming weeks” at the same price as Lumizyme, which retails for about $905 per 50-mg injection before discounts, according to Lumizyme, sold as Myozyme outside the U.S., reeled in €948 million ($1.11 billion) in global 2020 sales, Sanofi said in its annual report.

Sanofi estimates there are around 3,500 people in the U.S. with Pompe, which can manifest as infantile-onset Pompe disease and late-onset Pompe disease, with Nexviazyme's nod in the latter. 

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Pompe patients have a genetic deficiency or dysfunction of the enzyme acid alpha-glucosidase (GAA), which causes glycogen to build up in skeletal and heart muscles. Glycogen, which is the stored form of glucose, normally breaks down to release glucose into the blood, fueling cells, the FDA explained in an approval briefing. In Pompe patients, though, that excess glycogen can cause muscle weakness and even early death from respiratory or heart failure, the regulator said.

Nexviazyme targets the mannose-6-phosphate (M6P) receptor, which Sanofi flagged as the “key pathway for cellular uptake of enzyme replacement therapy in Pompe disease.” The drug is designed to boost cellular enzyme uptake and glycogen clearance in target tissues, the company added.

Late-onset Pompe symptoms can emerge at any age. Because of the “wide spectrum of clinical presentations” and the progressive nature of the disease, it can take “seven to nine years” before patients get an accurate diagnosis, Sanofi said in its release. As the disease progresses, people with late-onset Pompe may need to use a ventilator to help them breathe or a wheelchair to move around.

Nexviazyme, for its part, helped improve both respiratory function and walking distance in patients with late-onset disease in clinical studies, the company said.

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The FDA based its approval on Nexviazyme’s phase 3 COMET trial, which compared the drug’s efficacy to that of its enzyme-replacement predecessor alglucosidase alfa in 100 patients. At the 49-week mark, Nexviazyme patients scored 2.4 points higher on a standard lung function test used to measure respiratory muscle weakness than those on alglucosidase alfa.

Those results were good enough to confirm Nexviazyme’s noninferiority, though not quite enough to achieve statistical superiority over alglucosidase alfa, Sanofi said.

Meanwhile, patients on Nexviazyme were able to walk 30 meters farther than those in the alglucosidase alfa cohort at 49 weeks, according to a six-minute walk test used to measure functional endurance, Sanofi said.

The most common side effects reported by patients on Nexviazyme were headache, itchiness, nausea, hives and fatigue. Serious side effects cropped up in two patients who received Nexviazyme, versus three in patients on alglucosidase alfa.

Up until earlier this year, Nexviazyme had been locked in a race through the clinic with Amicus Therapeutics’ late-onset Pompe prospect AT-GAA (cipaglucosidase alfa and miglustat). In February, Amicus’ drug missed the mark in a phase 3 pitting it against Sanofi’s alglucosidase alfa.

Amicus’ study looked at 123 adult Pompe patients and used the six-minute walk test as its primary endpoint. At the 52-week mark, patients on Amicus’ drug could walk 21 meters farther than at baseline, versus seven meters farther for those in the alglucosidase alfa arm. Those results missed the bar for statistical significance.