NanoGLA, Possibly More Effective ERT for Fabry, Named Orphan Drug in EU

NanoGLA — a potentially more effective version of enzyme replacement therapy that delivers the missing enzyme in Fabry disease through tiny fatty vesicles — has been designated an orphan drug by the European Commission.

The decision was based on a positive recommendation by the Committee for Orphan Medicinal Products, a branch of the European Medicines Agency.

Orphan designation is given to investigative therapies with the potential to be safe and effective for rare, life-threatening, or chronically debilitating conditions that have no approved treatments, or where the potential therapy is showing significant benefit over existing treatments.

It is meant to accelerate the treatment’s clinical development and review by providing regulatory support and financial benefits, and to ensure marketing exclusivity for 10 years in Europe upon regulatory approval.

“With this designation we have made a major achievement, not only for Fabry patients, but also for other [diseases] that can benefit from this same approach, made possible by nanotechnology,” Nora Ventosa, PhD, the coordinator of the European Smart4Fabry project responsible for nanoGLA development, said in a press release.

Ventosa is a researcher at the Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and the Institute of Materials Science of Barcelona (ICMAB-CSIC) and the co-director of the Center of Nanotechnology and Molecular Materials (NANOMOL), in Spain.

In an informative video about the new therapy, Ventosa estimated that nanoGLA may be available to patients by 2026 should it succeed in all required clinical tests.

ERT, the current gold standard treatment for Fabry, involves delivering to patients a lab-made version of alpha-galactosidase A (Gal A) — the missing enzyme in Fabry disease —  restoring its normal function. ERT is given directly into a person’s bloodstream.

However, these Gal A versions have a relatively short half-life — the time it takes for the levels of a compound circulating in the body to drop to half of the original amount given. A large number of patients also develop antibodies against these proteins, limiting their effectiveness.

In addition, while Fabry disease also affects the central nervous system (CNS; the brain and spinal cord), existing ERTs cannot reach it due to their inability to cross the blood brain barrier. This semi-permeable barrier is intended to protect the brain, preventing potentially harmful and large molecules in the circulating blood from entering.

The goal of the Smart-4-Fabry project, now completed, was to develop a new ERT that delivered Gal A through liposomal nanocapsules, or tiny vesicle-like structures, that would remain longer in the body, promote fewer immune responses (antibodies), and more effectively target affected cells and organs than do current ERTs.

The nanoGLA product was created based on DELOS, Nanomol Technologies’ proprietary platform for the development of green and sustainable nanomedicines.

The nanovesicles surrounding Gal A are expected to protect the enzyme; improve its movement in, through, and out of the body; provide better delivery to target tissues, including the CNS; and reduce its toxicity and immune responses against it.

Notably, the project’s objective was to develop a new formulation with a 30–80% higher effectiveness, compared with current free Gal A-delivering ERTs.

Together, nanoGLA is anticipated to lower the doses needed and their total cost, and improve patients’ quality of life.

“The third-generation liposomal product we have developed in the project has demonstrated, at preclinical level, improved efficacy, compared to authorized enzyme replacement treatments, demonstrating that the strategy of supplying the affected cells with the GLA enzyme via the smart nanoliposome is highly successful,” said Ibane Abasolo, PhD, a researcher at CIBER-BBN and Vall d’Hebron Institute of Research.

Data from preclinical proof-of-concept studies showed that nanoGLA has a better pharmacological profile and higher efficacy than free Gal A in animal models. The therapy is now in the preclinical regulatory phase, an evaluation necessary to advance it into testing in people.

The four-year project, financed with €5.8 million from the European Commission’s Horizon 2020 program, involved the participation of a consortium of 14 academic institutions and private companies from Spain, Denmark, Austria, the U.K., and Israel.