Advances in Therapeutics-Enzyme Replacement Therapy: Long-Term Evaluation and New Approaches

The first enzyme replacement therapy (ERT) for a lysosomal storage disorder was marketed more than 30 years ago. We now have licensed products for 12 different conditions, and for a number of conditions, up to three different preparations are commercially available. These products were licensed on the basis of their ability to achieve pre-defined endpoints in clinical trials, but many have now been in clinical use for decades, and large amounts of real-world evidence have been generated. This has shown that not all treatments are equally effective and that there is still much unmet need, even for patients who have been treated for many years. Second-generation enzyme therapies are now being designed that will hopefully lead to improved clearance from currently hard-to-access cells and tissues, hence improving long-term clinical outcomes.