Sanofi announces results of CHMP re-examination of the New Active Substance status for avalglucosidase alfa, a potential new standard of care for the treatment of Pompe disease

NOVEMBER 12, 2021

The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) today reaffirmed its opinion that avalglucosidase alfa does not qualify as a New Active Substance (NAS). Sanofi does not agree with the CHMP’s conclusion on NAS status and is evaluating potential options for avalglucosidase alfa in the European Union. On July 23, 2021, the CHMP issued a positive opinion recommending marketing authorization for avalglucosidase alfa for the treatment of people with Pompe disease, a progressive and debilitating muscle disorder that impairs a person’s ability to move and breathe and a negative opinion on NAS designation. As a result, Sanofi requested a re-examination of the CHMP opinion in relation to the NAS conclusion.

“We are extremely disappointed with the CHMP’s opinion to deny designating avalglucosidase alfa as a new active substance,” said Bill Sibold, Executive Vice President of Sanofi Genzyme. “We believe the CHMP NAS process applies a narrow interpretation of the NAS principles which is not appropriate for biological therapies and does not account for the innovative structural changes to enzyme replacement therapies, such as avalglucosidase alfa. Moreover, it fails to consider the challenges of conducting clinical research in rare diseases and does not take into account the totality of the data, the nature of the disease, or ultimately the patient experience.”

Sibold added: “Today’s opinion fails to appropriately recognize and reward innovation and undermines the intended spirit of the NAS designation. This disincentivizes existing holders of marketing authorizations from pursuing further innovation in biological therapies with continued, high, unmet need, which ultimately has negative implications for patients and the future of scientific innovation in Europe. We strongly advocate that the EMA revisit and redefine the methodology used to assess the NAS status of biological products within the European Union, especially in the context of rare diseases.”

The July CHMP positive opinion recommending marketing authorization for avalglucosidase alfa for the treatment of people with Pompe disease reflects the robust data from the avalglucosidase alfa development program and the clinically meaningful improvements observed in respiratory function and movement endurance measures in people with Pompe disease compared to alglucosidase alfa, the current standard of care in Europe.

About NAS

New Active Substance (NAS) status is a designation considered by the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) as part of the review of a European Union (EU) Marketing Authorization Application (MAA). This is an important designation for a product, validating it as a differentiated, new, recommended treatment for patients. While somewhat technical in nature, NAS designation supports ongoing innovation in the development of potential, new treatments for patients by providing regulatory data protections.

When the CHMP concludes that (the active substance of) a product should be considered a NAS, it means that the CHMP views the product as being meaningfully different from another already-approved product at the level of molecular structure and/or with respect to clinical efficacy or safety properties.

About Pompe Disease

Pompe disease is caused by a genetic deficiency or dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA), which results in build-up of complex sugars (glycogen) in muscle cells throughout the body. The accumulation of glycogen leads to irreversible damage to the muscles, including the diaphragm muscle that supports lung function and skeletal muscles that affect mobility, as well as cardiac muscles in infantile-onset Pompe disease.


Pompe disease can present as infantile-onset Pompe disease (IOPD), the most severe form of Pompe disease with rapid onset in infancy, and late-onset Pompe disease (LOPD), which progressively damages muscles over time. LOPD symptoms may present at any age. However, due to the wide spectrum of clinical presentations and progressive nature of the disease, it can take seven to nine years before patients receive an accurate diagnosis. As the disease progresses, people with LOPD may require mechanical ventilation to help with breathing or a wheelchair to assist with mobility.

About avalglucosidase alfa

Avalglucosidase alfa is an enzyme replacement therapy designed to target the mannose-6-phosphate (M6P) receptor. With approximately 15-fold increase in M6P content compared to alglucosidase alfa, the current standard of care, avalglucosidase alfa is designed to help improve cellular enzyme uptake and thereby improve clearance of glycogen build-up in target tissues, the underlying disease mechanism in Pompe disease.
On August 6, 2021, the U.S Food and Drug Administration (FDA) approved the enzyme replacement therapy under the brand name Nexviazyme® (avalglucosidase alfa-ngpt) for the treatment of late-onset Pompe disease in patients one year of age and older. In addition, on September 27, 2021, the Japan Pharmaceuticals and Medical Devices Agency (PMDA) approved avalglucosidase alfa for the treatment of late-onset Pompe disease and infantile-onset Pompe disease. As part of Sanofi’s commitment to the Pompe disease community and to ensure broad access, Sanofi has decided to price avalglucosidase alfa at parity with alglucosidase alfa, the only currently available therapy for the treatment of Pompe disease and the comparator arm in the pivotal study.

Avalglucosidase alfa has received special designations from regulatory agencies across markets, typically reserved for medicines that are expected to represent significant improvements in safety or efficacy and help address unmet needs, underscoring its potential anticipated value. In the U.S., the medicine was granted a Priority Review, as well as Breakthrough Therapy and Fast Track designations. In South Korea, Taiwan, Australia, Switzerland, and Japan, the medicine was granted Orphan Designation. In the UK, the Medicines and Healthcare Products Regulatory Agency previously granted Promising Innovative Medicine (PIM) designation for avalglucosidase alfa. Avalglucosidase alfa was also included in early access programs in the UK via the Early Access to Medicines Scheme (EAMS) and in France via the Temporary Authorization for Use (ATU) program, with cohort ATU designation.