Sanofi’s investigational enzyme replacement therapy shows meaningful results in clinical manifestations of late-onset Pompe disease1

• Avalglucosidase alfa treatment demonstrated non-inferiority in the change in respiratory function using percent-predicted forced vital capacity (FVC), compared to alglucosidase alfa treatment (standard of care) in Pompe disease

READING, ENGLAND – 22 June 2020 – Sanofi’s investigational enzyme replacement therapy (ERT), avalglucosidase alfa, met the primary endpoint demonstrating non-inferiority in improving respiratory muscle strength, as measured by using percent-predicted forced vital capacity (FVC) in the upright position, compared to alglucosidase alfa (standard of care) in patients with late-onset Pompe disease (LOPD).¹

Patients treated with avalglucosidase alfa had a LS Mean 2.4-point difference in percent-predicted FVC compared to patients treated with standard of care (95% CI, -0.13 / 4.99) (p=0.0074) for non-inferiority.¹

“Late-onset Pompe disease is progressive and can have a substantial impact on a person’s quality of life. The hallmark symptoms of LOPD are impaired respiratory function and skeletal muscle weakness, which often leads to impaired mobility,” said Dr Mark Roberts, Consultant Neurologist at the Greater Manchester Neurosciences Unit at Salford Royal NHS Foundation Trust. “These data suggest avalglucosidase alfa, an investigational drug, could offer an effective treatment for LOPD and present an alternative treatment option for those living with the disease if approved for use in the future.”

Pompe disease is an inherited, genetic disorder which results in the deficiency of the enzyme 'acid alpha-glucosidase’ (GAA). Though the genetic defect that causes Pompe is present at birth, symptoms may appear at any time from birth to adulthood. This rare disease affects approximately 1 in every 40,000 in the UK, with approximately 200 people diagnosed.²

The trial’s primary endpoint was also assessed for superiority. Superiority statistical significance was not achieved for the avalglucosidase alfa arm (p=0.0626).

A key secondary endpoint in the trial measured mobility with the 6-minute walk test (6MWT). Patients treated with avalglucosidase alfa walked a mean of 30 meters farther than patients treated with standard of care (95% CI, 1.33/ 58.69). Other secondary endpoints assessed respiratory muscle strength, motor function, and quality of life.¹

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

**Formal statistical testing for all secondary endpoints was not conducted

The safety profile of avalglucosidase alfa was found to be comparable to alglucosidase alfa, the standard of care. Over the double-blinded 49-week period, 44 patients in the avalglucosidase alfa arm and 45 patients in the standard of care arm experienced an adverse event(s) (AEs). There were 6 patients with severe AEs in the avalglucosidase alfa arm and 7 patients in the standard of care arm. Fewer patients presented with serious adverse events (SAEs) in the avalglucosidase alfa arm (8 patients, including 1 patient with potentially treatment-related SAEs) compared to the standard of care arm (12 patients, including 3 patients with potentially treatment-related SAEs). In the standard of care arm of the trial, 4 patients had AEs leading to study withdrawal and 1 patient died due to an SAE of acute myocardial infarction (unrelated to treatment). In the avalglucosidase alfa arm, there were no patient discontinuations or deaths.¹

“We are encouraged by these results with avalglucosidase alfa in patients with late-onset Pompe disease,” said Marc Moodley, Medical Director UK & Ireland, Sanofi Genzyme. We are proud to be building on our heritage in this area, with the goal of bringing this potential new treatment to the Pompe community.”

Trial design

The randomised, double-blind, Phase 3, head-to-head COMET trial enrolled 100 previously untreated paediatric (≥ 3 years of age) and adult patients with LOPD across 56 centres in 20 countries. Patients were randomised to receive either avalglucosidase alfa 20 mg/kg or alglucosidase alfa (standard of care) 20 mg/kg intravenous infusion every two weeks for 49 weeks.

About Avalglucosidase alfa

Avalglucosidase alfa is an investigational enzyme replacement therapy for Pompe disease designed to improve the delivery of enzyme to the cells in the muscles, most notably into skeletal muscle. For more information about the avalglucosidase alfa clinical development program, please visit https://www.clinicaltrials.gov.

Avalglucosidase alfa does not currently have Marketing Authorisation in the EU/UK for any indication. Global regulatory submissions anticipated in the second half of 2020.