New data at ERS showed Xenpozyme (olipudase alfa) improved respiratory functions in adults with ASMD

In individuals with ASMD, a deficiency in acid sphingomyelinase—an enzyme that allows for the breakdown of a fatty substance called sphingomyelin—leads to lifelong accumulation of sphingomyelin in cells throughout the body which can damage vital organs, including the lungs. According to newly developed consensus clinical guidelines for ASMD, pulmonary dysfunction is a key clinical characteristic of ASMD caused by the accumulation of sphingomyelin throughout the respiratory system.

Additional data at the congress highlight the role that artificial intelligence could play in decreasing diagnosis delay of ASMD. Many ASMD patients endure years of suffering from disease complications before receiving an accurate diagnosis. Using electronic health records of patients with unexplained interstitial lung disease, researchers applied a machine learning derived algorithm to identify high-risk patients for ASMD diagnosis.

The Phase II ASCEND trial evaluated 36 adults with ASMD, excluding those with neurological disease, to receive either Xenpozyme or placebo. Following the primary analysis period which spanned 52 weeks, patients continued for up to two years in the open-label extension trial to assess the long-term efficacy and safety of Xenpozyme. These data from a post-hoc analysis of the primary analysis and open-label extension showed that Xenpozyme significantly improved respiratory function across four critical domains of interstitial lung disease, including pulmonary imaging as measured by clearance of ground glass opacities, gas exchange as measured by diffusion capacity of the lungs for carbon monoxide (DLco), lung mechanics as measured by forced vital capacity (FVC), and exercise capacity as measured by the maximum rate of oxygen (VO2) used during exercise.

Lung high-resolution computed tomography (HRCT) ground glass appearance score: Patients who received Xenpozyme in the primary analysis experienced a -0.51 decrease in mean value HRCT score. Of those, patients continuing Xenpozyme for up to two years in the extension trial experienced a further mean decrease of -0.04. Percent predicted DLco; The percent predicted DLco mean increase was 10.69% for patients receiving Xenpozyme in the primary analysis. Of those, patients continuing Xenpozyme for up to two years in the open-label extension experienced an additional mean increase of 4.94%. Percent predicted FVC: The percent predicted FVC mean increase was 5.78% for patients receiving Xenpozyme in the primary analysis. Of those, patients continuing Xenpozyme for up to two years in the extension trial experienced an additional mean increase of 1.15%. Percent predicted VO2: The percent predicted VO2 mean increase was 4.65% for patients receiving Xenpozyme in the primary analysis. Of those, patients continuing Xenpozyme for up to two years in the open-label extension experienced an additional mean increase of 1.81%.

Patients who switched from placebo to Xenpozyme following the primary analysis period also experienced improvements in HRCT score, percent predicted DLco, percent predicted FVC, and percent predicted VO2. Overall, nearly all treatment-related adverse events (99%) were mild or moderate, with one serious treatment-related adverse event, which was extrasystoles in a patient with previously documented cardiomyopathy. The most frequently reported adverse events were headache and transient transaminase elevations (i.e., increased levels of liver enzymes). No patient discontinued treatment due to adverse events.

Francesco Bonella, MD, PhD, Head of the Center for Interstitial and Rare Lung Diseases and Professor of Medicine at the Ruhrlandklinik University Hospital, Essen, Germany: “For patients with ASMD, respiratory disease most commonly manifests as interstitial lung disease, which is associated with respiratory failure and higher infection risk – a major contributor to patient mortality. In this analysis, we evaluated the effect of olipudase alfa on respiratory outcomes, and our findings showed that treatment with olipudase alfa provided sustained and progressive improvement in lung function, substantially modifying respiratory deterioration by addressing the underlying enzyme deficiency in ASMD.”