Sanofi’s avalglucosidase alfa, for Pompe disease, receives Promising Innovative Medicine designation[1]

• Avalglucosidase alfa is an investigational enzyme replacement therapy in development for Pompe disease^[2]
• Pompe is a rare disease that affects approximately 1 in every 40,000 in the UK, with approximately 200 people diagnosed^[3]

READING, ENGLAND – 29 September 2020 – Sanofi announced today that the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has issued a Promising Innovative Medicine (PIM) designation for avalglucosidase alfa in the treatment of Pompe disease.^[1]

PIM designations are given to medicinal products that are likely to offer a major advantage for patients.^[4] It is an early indication that a medicinal product is a promising candidate for the Early Access to Medicines Scheme (EAMS), intended for the treatment, diagnosis or prevention of a life-threatening or seriously debilitating condition with the potential to address an unmet medical need.^[5]

Pompe disease is a rare, 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 people in the UK, with approximately 200 people diagnosed.^[3]

“Pompe is a rare, progressive disease which has a substantial impact on a person’s health and quality of life,” said Dr Duncan Cole, Deputy Director, Clinical Reader in Medical Education, Hon. Consultant in Medical Biochemistry and Metabolic Medicine, University Hospital of Wales and Cardiff University. “The symptoms can occur at any age from birth, where the most severely affected infants usually have heart problems, skeletal muscle weakness and a life expectancy of less than two years, if untreated. Despite the availability of an approved treatment, there is still an unmet need for some patients living with this life-threatening and debilitating condition.”

The MHRA’s decision was based on data from the Phase III, pivotal COMET trial, which evaluated the safety and efficacy of avalglucosidase alfa compared to alglucosidase alfa (standard of care) in patients with late-onset Pompe disease^[6] and the Phase II mini-COMET trial, which evaluated the safety and exploratory efficacy of avalglucosidase alfa in patients with infantile-onset Pompe disease previously treated with alglucosidase alfa.^[7]

The Phase III COMET trial met its primary endpoint demonstrating non-inferiority of avalglucosidase alfa 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.^[6]

Patients treated with avalglucosidase alfa had a least square 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). The trial’s primary endpoint was also assessed for superiority. Superiority statistical significance was not achieved for the avalglucosidase alfa arm (p=0.0626).^[6]

In Phase II, mini-COMET study, the primary objective of assessing the safety of avalglucosidase alfa (20mg/kg and 40 mg/kg every two weeks) in patients with infantile-onset Pompe disease was achieved during the primary analysis period.^[7]

The safety profile of avalglucosidase alfa in both studies was found to be consistent with the standard of care.^[6],[7]

“The MHRA’s PIM designation marks an important milestone in Sanofi’s 20-year commitment to the Pompe community and we are delighted with the decision,” said Nicole Farmer, General Manager UK & Ireland, Sanofi Genzyme. “This not only recognises the life-threatening nature and high unmet need of Pompe disease but indicates that avalglucosidase alfa is an innovative medicine which could offer a potential new therapeutic option for patients with this rare disease.”

Avalglucosidase alfa does not have Marketing Authorisation in the EU/UK for any indication.

[1] Sanofi Data on File MAT-GB-2002809

[2] ClinicalTrial.Gov: Avalglucosidase alfa. Available at: https://clinicaltrials.gov/ct2/results?cond=&term=Avalglucosidase+alfa+&cntry=&state=&city=&dist=. Last accessed: September 2020.

[3] Association for Glycogen Storage Disease (AGSD). Pompe Disease (GSD2). Available at: https://agsd.org.uk/all-about-gsd/gsd-variants/pompe-disease-gsd2/. Last accessed: September 2020.

[4] Press release: 50th Promising Innovative Medicine (PIM) designation granted. Available at: https://www.gov.uk/government/news/mhra-grants-50th-promising-innovative-medicine-pim-designation. Last accessed: September 2020.

[5] MHRA Promising Innovative Medicine (PIM) Designation - Step I of Early Access to Medicines Scheme (EAMS). Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/375327/PIM_designation_guidance.pdf. Last accessed: September 2020.

[6] Sanofi Data on File MAT-GB-2002662

[7] Sanofi Data on File MAT-GB-2002821