EU Approval Urged for New Sanofi ERT Avalglucosidase Alfa
A committee of the European Medicines Agency (EMA) has recommended the approval of avalglucosidase alfa, a next-generation enzyme replacement therapy (ERT) developed by Sanofi Genzyme, for people with Pompe disease.
That recommendation, by the Committee for Medicinal Products for Human Use (CHMP), paves the way for marketing authorization to be granted by the European Commission for avalglucosidase alfa as a treatment for Pompe.
According to an EMA press release, avalglucosidase alfa — to be marketed as Nexviadyme — will be available as a 100 milligram (mg) powder, which is then diluted into a solution for infusion. The medication can be prescribed by physicians only.
Avalglucosidase alfa is designed to improve the delivery of acid alpha-glucosidase, known as GAA — the enzyme lacking in Pompe patients — to target cells. That will boost the clearance of glycogen, a sugar molecule whose abnormal buildup is a hallmark of Pompe disease.
Currently, Sanofi’s Lumizyme (alglucosidase alfa), an ERT marketed as Myozyme in Europe, is the only approved treatment for the rare genetic disorder.
In preclinical studies, avalglucosidase alfa had a 15 times higher cellular uptake when compared with Lumizyme, and comparable effects in glycogen clearance with a fivefold lower dose.
Sanofi Genzyme’s application seeking the approval of Nexviadyme was based on positive data from two ongoing clinical trials: the Phase 3 COMET (NCT02782741) and the Phase 2 Mini-COMET (NCT03019406) studies.
An application also has been submitted to the U.S. Food and Drug Administration. A decision is expected by Aug. 18.
The COMET trial is evaluating the therapy’s effectiveness as compared with Lumizyme in 100 previously untreated children and adults with late-onset Pompe disease, ages 3 and older.
Participants were randomly assigned to receive either avalglucosidase alfa (51 patients) or Lumizyme (49 patients). Both medicines were given intravenously (into the vein) every other week at a dose of 20 mg/kg for almost one year (49 weeks).
Following this initial treatment period, participants were able to join the study’s open-label part, in which all receive avalglucosidase alfa for more than 4.5 years (240 weeks). This trial is expected to conclude by September 2024.
Top-line COMET data showed meaningful improvements through week 49 in mobility and in respiratory muscle function, as measured through forced vital capacity (FVC), in patients treated with avalglucosidase alfa. The results thus far support that the next-generation ERT was at least not inferior to Lumizyme.
Improvements in parameters such as lower extremity muscle strength — meaning strength in the legs, ankles, and feet — and quality of life also were similar between the two therapies. Their safety profile also was similar.
The Mini-COMET study is evaluating the safety and preliminary effectiveness of avalglucosidase alfa in 22 children and adolescents with infantile-onset Pompe disease. All were previously treated with Lumizyme but failed to respond adequately.
These participants were randomly assigned to receive one of two doses (20 or 40 mg/kg) of avalglucosidase alfa, given every other week, or to their current stable dose of Lumizyme.
Six-month data showed that both doses of the ERT were well-tolerated, with no severe side effects. Children treated with avalglucosidase alfa also had lower or stable levels of the disease biomarkers creatine kinase and hexose (or glucose) tetrasaccharide.
This trial is expected to conclude in December 2024.
Avalglucosidase alfa had been designated an orphan medicine by the European Commission. Orphan drug status aims to encourage therapies for rare and serious diseases through a series of benefits, including 10 years of market exclusivity once the therapy is approved, and reductions in fees.
According to the press release, the EMA will now review the information available to determine if the orphan designation can be maintained.