Avalglucosidase alfa showed positive exploratory efficacy and was well-tolerated in Phase 2 trials in Pompe Disease

  • In patients with late-onset Pompe disease (LOPD), 5.5 years of safety and exploratory efficacy results showed avalglucosidase alfa was well-tolerated and stabilized pulmonary and motor function
  • In patients with infantile-onset Pompe disease (IOPD), results at six-months revealed treatment with avalglucosidase alfa was well-tolerated and improved or stabilized biomarkers of disease burden
  • Both data sets presented at the 16th Annual WORLDSymposium provide evidence supporting continued development of avalglucosidase alfa as a potential treatment for patients with Pompe disease

New Phase 2 data provided safety and preliminary efficacy results from two separate clinical trials evaluating treatment with avalglucosidase alfa, an investigational enzyme replacement therapy (ERT), in patients with late-onset Pompe disease (LOPD) and patients with infantile-onset Pompe disease (IOPD).

In both patient populations, avalglucosidase alfa was well-tolerated, with positive trends in exploratory efficacy measures. These data were presented today and will also be shared as oral presentations at the 16th Annual WORLDSymposium meeting on February 11, 2020.

Cambridge, MA--(BUSINESS WIRE)--“We are very encouraged by these results with avalglucosidase alfa in patients with either late-onset or infantile-onset Pompe disease, a progressive, debilitating and often fatal neuromuscular disease,” said Dietmar Berger, Head of Global Development, Sanofi. “Sanofi has a strong commitment to the Pompe disease community. We look forward to building on our legacy with the topline results of our Phase 3 study in late-onset Pompe disease later this year, with the goal of bringing a potential new treatment to both pediatric and adult patients.”

Phase 2 Data in Patients with Late-Onset Pompe Diseasei

NEO-EXT is an ongoing extension study of the NEO1 trial, which evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of avalglucosidase alfa in 24 patients with LOPD. As of July 2019, 17 patients were enrolled in NEO-EXT, receiving avalglucosidase alfa 20mg/kg once every other week.

At 5.5 years, avalglucosidase alfa demonstrated a safety profile consistent with the results from the six-month NEO1 study. One treatment-naïve patient discontinued NEO1 for a study drug-related serious adverse event (SAE; respiratory distress/chest discomfort). The most common treatment-related adverse events were fatigue, headache, nausea and rash (three patients each), dizziness, shortness of breath (dyspnea), redness of the skin (erythema), muscle spasm, muscle pain (myalgia), and pruritus (two patients each). No treatment-related life-threatening adverse events or deaths were reported in NEO-EXT. Among naïve and switch group patients, exploratory efficacy results showed stabilization in pulmonary and motor function as measured by forced vital capacity (FVC) and the six-minute walk test (6MWT), compared to the natural decline in these patients due to disease and/or age. The mean percent predicted change from baseline as measured by FVC was -0.331% per year for switch patients and +0.396% per year for naïve patients. The mean percent predicted change from baseline as measured by the 6MWT was -1.216% per year for switch patients and -0.965% per year for naïve patients. 

“Results from the NEO-EXT study are consistent with the safety and preliminary efficacy data reported in the NEO1 study with avalglucosidase alfa in late-onset Pompe disease,” said Mazen M. Dimachkie, M.D., lead investigator of the NEO-EXT study and Professor of Neurology, Vice-Chairman of Research Programs and Director of the Neuromuscular Division at Kansas University Medical Center. “Advancing science around the treatment of Pompe disease is very important, as this rare genetic condition affects multiple organs and is complex to manage.”

Phase 2 Data in Patients with Infantile-Onset Pompe Diseaseii

Mini-COMET is an ongoing Phase 2, open-label, ascending-dose, three-cohort study of avalglucosidase alfa in 22 patients under 18 years of age with IOPD, who were previously treated with alglucosidase alfa and showed incomplete treatment response in pre-specified clinical outcomes. Patients in cohort one receive 20mg/kg of avalglucosidase alfa every other week, patients in cohort two receive 40mg/kg of avalglucosidase alfa every other week, and patients in cohort three were randomized to receive 40mg/kg of avalglucosidase alfa every other week or alglucosidase alfa at their current stable dose (within a range of 20mg/kg every other week to 40mg/kg weekly).

At six months, results showed that avalglucosidase alfa was well-tolerated at 20mg/kg and 40mg/kg dose every 2 weeks. The most common adverse events reported in this trial were mild to moderate, including vomiting and pyrexia (six patients each), upper respiratory tract infections (five patients), and cough and rash (four patients each). No serious or severe treatment-related adverse events occurred. No adverse events resulted in permanent treatment discontinuation or death. Biomarkers of disease burden decreased or stabilized in all cohorts from baseline to week 25 (see table below).

Biomarkers of Disease Burden

Median change (%) from Baseline to Week 25


Cohort 1, Avalglucosidase alfa

20 mg/kg qow

Cohort 2, Avalglucosidase alfa

40 mg/kg qow

Creatine kinase (IU/L)

-106.00 (-30.07%)

-588.00 (-49.49%)

Hexose tetrasaccharide (mmol/mol)

  1.59 (2.43%)

  -27.44 (-33.30%)



Cohort 3, Alglucosidase alfa

Variable dosing*

Cohort 3, Avalglucosidase alfa

40 mg/kg qow

Creatine kinase (IU/L)

  -9.50 (-0.56%)

-149.00 (-38.62%)

Hexose tetrasaccharide (mmol/mol)

    -2.70 (-19.81%)

  -18.49 (-36.38%)

*Alglucosidase alfa dosing ranged from 20mg/kg qow to 40mg/kg weekly

IU, international unit; L, liter; mmol, millimole; m, mole; qow, every other week

“These safety and tolerability results are promising for the future development of avalglucosidase alfa treatment in infantile-onset Pompe patients,”
said David Kronn, M.D., lead investigator of the mini-COMET study and Associate Professor of Pediatrics at New York Medical College. “Exploratory disease biomarker data showed trends of decrease or stabilization in most patients at six months of treatment, which is very encouraging. Additionally, no patients discontinued avalglucosidase alfa during the trial.”

About Pompe Disease

Pompe disease is a progressive, debilitating and often fatal neuromuscular disease caused by a genetic deficiency or dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA) that results in the build-up of glycogen in the body’s cells. The disease affects an estimated 50,000 people worldwide and can occur at any age from infancy to late adulthood. Pompe disease is often classified as late-onset Pompe disease (LOPD) or infantile-onset Pompe disease (IOPD). Patients with LOPD typically present any time after the first year of life to late adulthood. The hallmark symptoms of LOPD are skeletal muscle weakness, which often leads to walking disability, and reduced respiratory function. Patients often require wheelchairs to assist with mobility and may require mechanical ventilation to help with breathing. Respiratory failure is the most common cause of mortality in patients with Pompe disease. Pompe disease is classified as IOPD when symptoms begin prior to one year of age and there is impact to the heart in addition to skeletal muscle weakness. 

About Avalglucosidase Alfa

Avalglucosidase alfa is an investigational ERT for Pompe disease that has been designed for improved receptor targeting and enzyme uptake, with the aim of enhancing glycogen clearance in target tissues.iii In addition to the NEO-EXT and mini-COMET trials, avalglucosidase alfa is under investigation in the COMET trial, a Phase 3 study to compare the efficacy and safety of biweekly infusions of avalglucosidase alfa and alglucosidase alfa in pediatric and adult patients with LOPD who have not previously received treatment. For more information on these trials, please visit https://www.clinicaltrials.gov.

Avalglucosidase alfa has not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory agency worldwide for the use under investigation.

About Sanofi

Sanofi is dedicated to supporting people through their health challenges. We are a global biopharmaceutical company focused on human health. We prevent illness with vaccines, provide innovative treatments to fight pain and ease suffering. We stand by the few who suffer from rare diseases and the millions with long-term chronic conditions.

With more than 100,000 people in 100 countries, Sanofi is transforming scientific innovation into healthcare solutions around the globe.

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i ClinicalTrials.gov Identifier: NCT02032524

ii ClinicalTrials.gov Identifier: NCT03019406

iii Zhu Y, et al. J Biol Chem. 2004 Nov 26;279(48):50336-41

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