Real-world outcomes from a series of patients with late onset Pompe disease who switched from alglucosidase alfa to avalglucosidase alfa

Abstract

Introduction: Pompe disease is an inherited, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase and accumulation of glycogen in tissues, resulting in cellular dysfunction, muscle damage, and functional disabilities. Enzyme replacement therapy with alglucosidase alfa (Myozyme/Lumizyme) has led to better outcomes, but many patients have plateaued or declined despite treatment. The second-generation ERT avalglucosidase alfa (Nexviazyme) was designed to have enhanced cellular uptake via the conjugation of additional bis-mannose-6-phosphate residues. There have been trials comparing the efficacy of alglucosidase and avalglucosidase, but there remains a need for more real-world data on patients who switched from alglucosidase to avalglucosidase. Methods: A chart review was conducted on n = 15 patients with late-onset Pompe disease followed at a single center who switched from alglucosidase to avalglucosidase and continued for at least 6 months. Results: A total of n = 8/15 patients received alglucosidase for more than 3 years prior to switching, and n = 7/15 received it for more than 5 years prior to switching. There were statistically significant improvements in CK, Hex4, and AST with mean differences of -104.8 U/L, -3.0 mmol/molCr, and -14.7 U/L, respectively, post-switch. 6-Minute Walk Test; comfortable gait speed; Gait, Stairs, Gower, Chair; and Quick Motor Function Test scores improved or stabilized in most patients post-switch (n = 8/12, n = 11/12, n = 9/12, n =7/11, respectively). Of n = 7 patients with pulmonary function testing, n = 4/7 had improved upright FVC. Patient-reported outcomes revealed improvements in dyspnea (n = 4/4), physical function (n = 3/4), fatigue (n = 2/3), and lower back pain (n = 3/3). Avalglucosidase was well tolerated without infusion-associated reactions, and all n = 7 patients on home infusions continued receiving ERT at home. Anti-drug antibodies were seen in n = 9/10 of patients on alglucosidase and n = 8/13 of those on avalglucosidase, with titers below 12,800 in a majority of patients. We also present the first outcome data for a patient with LOPD who is non-ambulatory and a full-time wheelchair user; she demonstrated meaningful improvements in quality of life and motor function with the switch. Discussion: In summary, improved outcomes were seen in most patients, with a subset whose decline persisted. This study presents evidence that switching from alglucosidase to avalglucosidase may be associated with improved outcomes in certain patients with LOPD.

Keywords: alglucosidase alfa; avalglucosidase alfa; enzyme replacement therapy; glycogen storage disease type 2; late-onset Pompe disease (LOPD); lysosomal storage disease (LSD).

FIGURE 1

ERT history. Alglucosidase regimens are indicated by shades of blue, avalglucosidase regimens are indicated by shades of green, and other regimens are indicated by patterned gray bars.

FIGURE 2

CK, Hex4, and AST trends. Baseline values are the last known values prior to initiating ERT. Alglucosidase values are the last known values prior to the switch. Avalglucosidase values are the most recent values available in patient’s chart. Dotted horizontal lines are upper limits of normal.

FIGURE 3

Upright forced vital capacity. Percent predicted upright forced vital capacity results for patients 1, 2, 3, 4, 5, 11, and 12. Color-coded vertical bars represent the starting points of ERT regimens.

FIGURE 4

Patient-Reported Outcomes (PROs). PROs for dyspnea, physical function, fatigue, and lower back pain. Higher dyspnea scores (range 0–99) indicate increased severity of dyspnea with common daily activities. Higher physical function scores (range 20–99) indicate increased physical function and ability to carry out daily life activities. Higher fatigue scores (range 8–40) indicate increased fatigue on average over the past week. Higher lower back pain scores (range 0–50) indicate greater severity of lower back pain and impact on life.