Top 10 Fabry disease stories of 2023

In 2023, Fabry Disease News brought readers consistent coverage of the most recent developments in scientific research and clinical trials for Fabry disease.

Here are the 10 most-read news stories of the year, along with a brief description of what made them relevant for our readers.

No. 10 – Nerves that control heartbeat may be damaged in Fabry

Individuals with Fabry frequently experience dysfunction in the nerves responsible for regulating the heartbeat, a study found. Its researchers noted that such impairment may be a potential prognostic indicator for evaluating cardiac issues associated with the disease. More severe impairment was observed in patients with more advanced symptoms and a scarred or enlarged heart.

While looking at how damaged these nerves are may serve to predict how likely it is for someone with Fabry to develop heart disease, the researchers noted that the advanced imaging techniques used in the study are unlikely to be adopted in clinical practice due to their costs and the need for very specialized equipment.

No. 9 – Galafold may diminish heart alterations, enhance exercise tolerance

In Fabry patients with heart involvement who were previously untreated, taking the approved medication Galafold (migalastat) every other day for up to 18 months stabilized indicators of heart disease. Those who benefited the most were younger and had less severe heart disease.

The oral medication also tended to improve the amount of exercise patients could tolerate.

Galafold is a chaperone therapy from Amicus Therapeutics that’s designed to restore alpha-gal A activity —  the enzyme mutated in Fabry — in patients carrying certain types of disease-causing mutations.

No. 8 – Clinical development of FLT190 for Fabry paused by Freeline

In April, Freeline Therapeutics decided to pause the clinical development of FLT190, its experimental gene therapy for the treatment of Fabry disease. The decision was taken for strategic reasons as the company focuses its resources on advancing FLT201, a gene therapy for Gaucher disease.

As a result, Freeline terminated MARVEL-1 (NCT04040049), an open-label Phase 1/2 clinical trial that aimed to test the safety and efficacy of FLT190 in up to 15 men with Fabry disease.

FLT190 uses a modified and harmless liver-directed adeno-associated virus to deliver a healthy version of the GLA gene, which provides the instructions to produce alpha-gal A.

No. 7 – Adherence to Galafold is high among adults with Fabry

Adults with Fabry disease demonstrated strong adherence to at-home Galafold treatment — which must be taken every other day at the same time of day on an empty stomach — for a duration of two years.

The findings of the MALTA-FABRY study (NCT03683966) also highlighted a consistent quality of life seen among patients, which was accompanied by decreasing levels of pain and physical limitations over time.

Forgetting to take the capsule was the main reason for not sticking to the schedule; physicians were encouraged to stress among patients the importance of adherence, potentially by building Galafold into a daily routine to make it easier to remember.

No. 6 – Elfabrio may soon be available in England at low or no cost

In September, the National Institute for Health and Care Excellence (NICE) in England recommended that Elfabrio (pegunigalsidase alfa), approved in the country for Fabry patients, be covered by the national health service and provided at low or no cost to eligible adults.

The recommendation came a couple of weeks after Elfabrio, developed jointly by Chiesi Global Rare Diseases and Protalix BioTherapeutics, was approved in the U.K. as a long-term enzyme replacement therapy for adults with Fabry.

Elfabrio delivers a functional version of the Gal A enzyme via infusion into a patients’ bloodstream. The therapy was created with Protalix’s plant-based ProCellEx platform, and was chemically designed to provide a long half-life — that is, the time required for the blood level of a medication to reduce by half.

No. 5 – ST-920 gene therapy gets on FDA’s fast track

The U.S. Food and Drug Administration (FDA) granted fast track designation to Sangamo Therapeutics’ ST-920, (isaralgagene civaparvovec), a gene therapy candidate for Fabry disease that’s headed toward Phase 3 clinical testing.

With the designation, Sangamo gets to have more frequent interactions with the FDA throughout the clinical development of ST-920. The therapy showed promising interim data in an ongoing Phase 1/2 clinical trial called STAAR (NCT04046224).

ST-920 is engineered to provide a functional copy of the GLA gene to liver cells. This enables the liver cells to produce a functional variant of the alpha-Gal A enzyme, which can then be distributed throughout the body to assist in the clearance of toxic accumulation of fatty molecules such as globotriaosylceramide (Gb3). Such accumulation is a hallmark of Fabry disease.

No. 4 – mRNA treatment may restore enzyme missing in Fabry

In the lab, mRNA carrying blueprints to produce a correct version of the Gal A enzyme restored its activity in heart cells derived from two people with the disease. While it is still too early to translate these findings into the clinic, researchers in Australia say they support further development of the mRNA treatment for heart disease related to Fabry.

No. 3 – FDA places 4D-310 clinical program on hold

In February, the FDA placed a hold on the clinical program for 4D-310, a gene therapy being developed by 4D Molecular Therapeutics for Fabry disease. The decision came shortly after three of the six adults who had been dosed in the company’s Phase 1/2 clinical trials developed atypical hemolytic uremic syndrome (aHUS), a disease that results in the breakdown of red blood cells.

The company was continuing to working with the FDA in November on a plan to lift the hold on a Phase 1/2 clinical trial (NCT04519749) taking place in the U.S. That plan involves the use of the immunosuppressants rituximab and sirolimus to lower the risk of aHUS.

No. 2 – Europe’s decision on Elfabrio was awaited after positive opinion

In late February, Elfabrio — then still called PRX-102 — received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), which is part of the European Medicines Agency. A decision on whether to approve Elfabrio to treat adults with Fabry in Europe was pending. A positive decision came a couple of months later, when Elfabrio was granted marketing authorization by the European Commission.

No. 1 – Elfabrio wins FDA approval to treat adults with Fabry

A few days after the treatment’s approval in Europe, the FDA gave its green light to Elfabrio as a long-term enzyme replacement therapy for Fabry. The medication is given as an intravenous, or into-the-vein, infusion every two weeks. Per its label, Elfabrio is approved to treat adults with a confirmed diagnosis of Fabry disease.

We at Fabry Disease News hope these stories and all of our reporting in 2023 helped to inform the Fabry community and improve the lives of everyone affected by the disease. We look forward to continuing to be of service to the community in 2024.

We wish all our readers a very happy new year!