Fabry Awareness Month 2025: Week One

Advancements in Fabry Disease Treatments

Another year has flown by and Fabry Awareness Month has arrived. Time definitely moves faster as you get older! I have thought about the topics I’m going to cover this month and realise that, since my diagnosis almost ten years ago, so much has changed - Fabry Research continues to explore treatments and therapies to help with this condition. I am truly thankful for that.

So in this first article for Fabry Awareness Month 2025, I’m going to look at how the treatment of Fabry Disease has evolved over the last ten years.

For those unfamiliar with Fabry, it is a rare genetic disorder caused by a deficiency of the enzyme alpha galactosidase A, leading to the accumulation of glycosphingolipids in various tissues. Over the past decade, significant progress has been made in the treatment of Fabry disease.

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Enzyme Replacement Therapies (ERT)

For many years, enzyme replacement therapies have formed the cornerstone of Fabry disease management. Two main ERTs have been widely used:

• Agalsidase alfa (Replagal):

Licensed in the early 2000's, Replagal continues to be an important treatment option. Over the last ten years, clinicians have refined dosing strategies and improved infusion protocols to enhance patient outcomes.

Learn more at ClinicalTrials.gov

• Agalsidase beta (Fabrazyme):

Introduced shortly after agalsidase alfa, Fabrazyme has also maintained a critical role in reducing glycosphingolipid accumulation. It remains a mainstay of therapy and continues to be part of trials to improve efficacy and outcomes.

For further details, refer to ClinicalTrials.gov

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Pharmacological Chaperone Therapy

A significant shift in treatment came with the approval of Migalastat (Galafold) in 2016. This oral therapy works by stabilising the patient’s own enzyme in individuals with amenable mutations. I was hopeful that our family would be put on this treatment when we were first diagnosed but, unfortunately, our mutation was not amenable.

Migalastat offers the convenience of an oral medication—eliminating the need for biweekly infusions—and has broadened treatment options for patients meeting the genetic criteria.

Further insights are available on the European Clinical Trials Register

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Pegunigalsidase Alfa (Elfabrio) Treatment: A new Enzyme Replacement Treatment (ERT)

In addition to the established treatments, a new therapy known as Elfabrio has recently been sanctioned for use in adults in the UK.

Elfabrio is an alternative to the two current ERT treatments. It states it’s plant-based which I found intriguing. Looking into this a bit more (and I think I understand this – please correct me if I’m wrong) Elfabrio's active ingredient, pegunigalsidase alfa, is a recombinant human α-Gal-A enzyme. But while the enzyme itself is human, it's produced using a plant cell-based system and then chemically modified with PEGylation, a plant-derived compound, and this is the basis for the "plant-based" label.

I don’t know anyone who is on this treatment, but I have heard from some that they may be moving to this in the future and that there is the possibility of longer durations between infusions. This is interesting and if I hear more then I’ll update as appropriate. In the meantime you can find more information about Elfabrio at ClinicalTrials.gov

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Emerging and Investigational Therapies

Recent years have also seen exciting developments in investigational therapies aimed at addressing unmet needs in Fabry disease:

• Substrate Reduction Therapies (SRT):

Agents like Lucerastat are being studied as an alternative or addition to ERT by limiting the synthesis of glycosphingolipids. While these therapies remain investigational, early studies are promising. Ongoing Trial information can be found on ClinicalTrials.gov

• Gene Therapy Approaches:

Novel gene therapies, including AAV based treatments like FLT190, are in early phase trials. These approaches aim to provide long term correction of the enzyme deficiency, potentially reducing or eliminating the need for regular infusions.

Ongoing trials can be followed on ClinicalTrials.gov

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Improvements in Delivery and Patient Care

Beyond the medications themselves, the delivery of Fabry disease treatments has evolved significantly. Initiatives like home infusion programs and enhanced patient support services have improved treatment adherence and overall quality of life by reducing the need for frequent hospital visits. I honestly don’t know if I could cope with the bi-weekly infusions if I needed to rack up to the hospital every time, so I am so thankful that homecare is an option for Fabry treatment.

I really must pay tribute to these hard-working home-care nurses, and the team members we don’t see who make sure we get our appointments booked, our prescriptions filled and our deliveries made. You really make a huge difference to the quality of life for my family – and I’m sure that goes for all the people who receive your services.

My experience within the Specialist Centres has seen some changes during my ten years of treatment. Certainly the focus on bringing together multi-disciplinary teams (MDT’s) has had a positive effect on my treatment and I find the discussions with my specialist metabolic consultant are far more rounded due to this; encompassing all elements of my issues in a depth that wasn’t possible before the advent of the MDT meetings. And, as I’m paying tribute, I must say that the Specialist teams I have encountered over the last ten years have been largely amazing (with only one huge exception – and those familiar with my blog and talks will know what I mean here), including the Consultants and the Specialist Nurses. And it’s a tough gig, especially when dealing with families who find their lives turned upside down with this unpredictable, and often invisible, rare condition.

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Conclusion

The last ten years have witnessed both consolidation and innovation in the treatment of Fabry disease. Enzyme replacement therapies and the introduction of oral medications like migalastat have provided patients with valuable options. Meanwhile, emerging therapies—including substrate reduction, gene therapy, and the recently approved Elfabrio treatment—offer hope for even more effective management in the future.

Staying informed through reputable sources such as ClinicalTrials.gov and the EU Clinical Trials Register is really useful for patients, caregivers, and clinicians as the landscape of Fabry disease treatment continues to evolve. Patient organistions like the MPS Society in the UK is a fabulous support network and helps keep up to date with the latest treatment advice and innovations.

I hope the post is useful. Let me know what else you would like to read about in my blog. See you next week.

Loretta