Sanofi eyes extending Nexviazyme into infantile Pompe

Sanofi is preparing to expand the use of its Pompe therapy Nexviazyme, currently approved only for late-onset cases of the rare disease in some markets, to include patients who are diagnosed in infancy.

Nexviazyme (avalglucosidase alfa) met all the primary and secondary endpoints in the phase 3 Baby-COMET study in infantile-onset Pompe disease, setting up regulatory filings to extend the drug's label in the US before the end of the year. It is already approved for both late- and infantile-onset Pompe in Europe.

The medicine – sold as Nexviadyme in some markets – is a key growth product for Sanofi's rare disease operations, with sales rising more than 21% last year to reach €790 million, as its older Pompe therapy Myozyme/Lumizyme (alglucosidase alfa) shrank by the same margin to €519 million. Most of that decline stemmed from patients switching to Nexviazyme from the older drug.

Both drugs are recombinant versions of the enzyme alpha-glucosidase, which is deficient in Pompe disease, leading to the accumulation of glycogen to toxic levels that damage muscle cells. However, Nexviazyme is designed to offer increased take-up of the enzyme into muscle and enhanced glycogen clearance.

Infantile-onset Pompe is the most severe and rapidly progressing form of the disease, with symptoms typically appearing in the first few months of life, and it generally means that the person has almost completely missing or severely deficient levels of the enzyme. It is characterised particularly by cardiomyopathy, which can quickly lead to heart failure and death.

The late-onset form tends to be milder and slower-progressing, and can generally be detected from late infancy – 12 months or later – through childhood and into adulthood. Its main differentiator from infantile-onset Pompe is that patients do not tend to develop cardiomyopathy. Late-onset is more common, accounting for around 85% of all diagnosed Pompe cases.

Some patients with infantile-onset Pompe will already be treated off-label with Nexviazyme in the US, but the results of the Baby-COMET study and the likely extension to the drug's label will reassure clinicians and encourage them to use it more widely in this patient population.

The results of the single-arm study, which investigated an intravenous dose of Nexviazyme administered every two weeks to treatment-naïve infants zero to six months of age, showed a higher proportion were still alive and free of invasive ventilation at 52 weeks compared to an external comparator group treated with alglucosidase alfa.

There was also a significant improvement in the proportion of participants alive and free of invasive ventilation at 18 months of age, and numerical improvements in other metrics of disease progression at 52 weeks, according to Sanofi, which intends to present the data in full at a future medical congress.

"These positive results offer the potential to expand access of Nexviazyme to more patients and families facing a condition with limited treatment options in the earliest months of life," said Christopher Corsico, global head of development at Sanofi.

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