Sanofi pumps up its Pompe portfolio with Maze deal

In licensing Maze’s oral contender, the group has made another bet against gene therapies.

Sanofi has gambled against gene therapy before, and now it has done so again. The group today licensed Maze Therapeutics’ MZE001, an oral contender for Pompe disease.

Treatments for Pompe already exist in the form of enzyme replacement therapies, and here Sanofi dominates the market with Myozyme (also known as Lumizyme) and its newer drug Nexviazyme. But competition could be coming from the likes of Amicus’s AT-GAA and eventually gene therapies, a look at the pipeline shows.

The move for MZE001 therefore looks like a shoring up of Sanofi’s existing franchise. Maze reckons that its project, a glycogen synthase 1 (GYS1) inhibitor, could be used both as monotherapy and in combination with enzyme replacement.

Enzyme replacement replacement

Pompe disease is caused by mutations in the GAA gene, which encodes the enzyme acid alpha glucosidase. This enzyme usually breaks down glycogen, which builds up in Pompe patients, leading to muscle damage.

According to Maze, enzyme replacement is only partially effective in clearing glycogen. MZE001 inhibits GYS1 – the enzyme that controls glycogen production – and could address the “therapeutic gap”, the company says.

Sanofi apparently agrees. The deal looks to have been triggered by phase 1 data released this year, showing reductions in glycogen in healthy volunteers. Maze had planned to start a phase 2 trial this year; this will now be Sanofi's responsibility.

The French group is not making a big bet here, however. The collaboration is worth $150m in up-front cash and future equity, the companies said, without breaking this down. $600m in milestones are up for grabs under the agreement, which also covers Maze’s back-up GYS1 assets.

Gene therapies, offering the promise of a once-and-done treatment, could pose a big threat to both enzyme replacement and MZE001. But regulators have been cautious about such projects, particularly in diseases with existing treatments, given questions about durability and toxicity.

Dwindling excitement around gene therapies was illustrated by Amicus’s exit from the field last year; the group had joined the gene therapy chase in Pompe and other diseases in 2018.

A more advanced candidate, Astellas’s AT845, was placed on clinical hold last June after a serious adverse event of peripheral sensory neuropathy. This was lifted in January, and in February Astellas reported initial data from four patients in the phase 1/2 Fortis trial. Three of the four have come off enzyme replacement, but three participants also developed transient transaminitis deemed possibly related to AT845. Astellas said these cases were resolved with changes to immune suppression.

Roche’s RG6359 is also still in play, but the group recently tempered sales expectations for this project.

Given current gene therapy doubts, perhaps Sanofi is wise to stick with something more traditional.

The Pompe disease landscape
Product/project Company Description Note
Myozyme (infant onset)/Lumizyme (late onset) Sanofi IV enzyme replacement therapy (alglucosidase alfa) Approved 2010
Nexviazyme/Nexviadyme Sanofi IV enzyme replacement therapy (avalglucosidase alfa) Approved 2021
AT-GAA (Pombiliti + miglustat) Amicus IV enzyme replacement therapy (cipaglucosidase alfa) + oral stabiliser FDA inspection due Q2 2023; decision expected Q3 2023 
Phase 1/2
AT845 Astellas (via Audentes) GAA gene therapy Fortis, initial data Feb 2023; had been on hold
SPK-3006 (RG6359) Roche (via Spark) GAA gene therapy Resolute completes Oct 2023
ACTUS-101 (AAV2/8-LSPhGAA) Bayer (via Askbio) GAA gene therapy NCT03533673 completes Apr 2025
Phase 1
MZE001 Maze Therapeutics Oral glycogen synthase type 1 inhibitor NCT05249621, positive data in Feb 2023
GAA=glucosidase alpha acid. Source: Evaluate Pharma &

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