ENZYME REPLACEMENT THERAPY |

Abbreviations: ASD = autism spectrum disorder; CDI = clostridium difficile infection; ENPP1 = ectonucleotide enzyme replacement therapy;

= Graft versus host disease; IL-18 = interleukin 18; IV = intravenous; SQ = subcutaneous with improved lung function similar to the improvement seen with the other therapy.8 Long-term extension results from the phase 3 COMET study showed, after nearly two years, that treatments with avalglucosidase alfa in both primary and extension periods led to a 2.65-point improvement in forced vital capacity compared to baseline.9 Patients treated with avalglucosidase alfa during primary and extension periods showed an average increase of 18.6 meters in walking disease measured by a six-minute walking test compared with distance at baseline.9

Avalglucosidase alfa is currently being investigated as an alternative treatment option for infantile-onset Pompe disease (IOPD).9 The phase 3 Baby-COMET trial started in September 2021 in participants under six months with a primary endpoint of proportion of participants who are alive and free of invasive ventilation at week 52.9

Side effects associated with avalglucosidase alfa include headache, fatigue, diarrhea, nausea, joint pain, dizziness, muscle pain, itching, vomiting, difficulty breathing, skin redness, paresthesia, and skin welts, while more serious reactions include hypersensitivity.7

Management Opportunities

Growth of the ERT landscape is trending, and the market is anticipated to grow significantly over the next decade.10 A rise in prevalence and diagnoses of rare LSDs will drive much of this growth.10 As this market continues to grow and more treatment options become available for these rare LSDs, payer focus on management will become increasingly important. Management strategies that aim to allow access to the patient population that will benefit most from these therapies will be key to managing costs and improving outcomes.

References

1. “What is Enzyme Replacement Therapy and How Does It Work?” Infusion Associates, https://infusionassociates.com/what-is-enzymereplacement-therapy.

2. “Enzyme Replacement Therapy.” LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, 10 Mar. 2016, https://www. ncbi.nlm.nih.gov/books/NBK548796.

3. “FDA approves first enzyme replacement therapy for rare alphamannosidosis.” U.S. Food & Drug Administration, 17 Feb. 2023, https://www.fda.gov/drugs/news-events-human-drugs/fda-approvesfirst-enzyme-replacement-therapy-rare-alpha-mannosidosis.

4. Borgwardt, Line, et al. “Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial.” Journal of Inherited Metabolic Disease, 2018, https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC6326984.

5. Meglio, Marco. “FDA Approves Enzyme Replacement Therapy

Pegunigalsidase Alfa for Fabry Disease.” NeurologyLive, 10 May 2023, https://www.neurologylive.com/view/fda-approves-enzymereplacement-therapy-pegunigalsidase-alfa-for-fabry.

6. Meglio, Marco. “Pegunigalsidase Alfa Demonstrates Efficacy in Phase 3 Fabry Disease Study.” NeurologyLive, 3 Mar. 2021, https:// www.neurologylive.com/view/pegunigalsidase-alfa-demonstratesefficacy-phase-3-fabry-disease.

7. “FDA Approves New Treatment for Pompe Disease.” U.S. Food & Drug Administration, 6 Aug. 2021, https://www.fda.gov/news-events/pressannouncements/fda-approves-new-treatment-pompe-disease.

8. Diaz-Manera, Jordi, et al. “Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial.” Lancet Neurology, Dec. 2021, https://pubmed.ncbi.nlm.nih.gov/34800399/.

9. “Nexviazyme® (avalglucosidase alfa) shows sustained improvements in respiratory function and mobility in patients with Pompe disease.” Sanofi, 8 Feb. 2022, https://www.sanofi.com/en/media-room/press-releas es/2022/2022-02-08-14-00-00-2380936.

10. Smita, N., et al. “Enzyme Replacement Therapy Market by Product, Disease, and End User: Global Opportunity Analysis and Industry Forecast, 2021-2030.” Enzyme Replacement Therapy Market, Sept. 2021, https://www.alliedmarketresearch.com/enzyme-replacementtherapy-market-A10949.