Early therapeutic intervention with enzyme replacement therapies (ERTs), along with a multidisciplinary follow-up, should be initiated at a young age in Fabry patients to promote the best outcomes and prevent disease progression in both adult and pediatric patients.
These are the conclusions of the review, “Therapeutic goals in Fabry disease: Recommendations of a European expert panel, based on current clinical evidence with enzyme replacement therapy,” published in Molecular Genetics and Metabolism.
Fabry disease is a genetic disorder characterized by deficient levels of the α-galactosidase A enzyme, due to mutations in the GLA gene. As a result of this enzyme deficiency, an intermediate molecule called globotriaosylceramide (Gb3 or Gl-3) builds up inside cells, leading to organ damage.
ERTs that use an engineered form of the α-galactosidase A enzyme slow or prevent the progression of the disease. Since 2001 two forms of injectable ERTs are available in Europe: Replagal (agalsidase alfa) and Fabrazyme (agalsidase beta). In the United States only Fabrazyme is available.
Several clinical trials and real-world clinical reports have demonstrated that these ERTs can effectively manage Fabry’s symptoms. But outcomes depend on when treatment begins and the extent of organ damage.
Identifying early biomarkers of Fabry disease has become a major focus of the scientific and medical community to begin treatment before irreversible damage occurs. However, this has been a challenge because disease symptoms are highly variable, depending on patients’ age, gender, and genetics.
Sponsored by Sanofi Genzyme, a panel of 26 European experts in Fabry disease met to form consensus recommendations on therapeutic goals of ERT at different stages of the disease. They reviewed clinical data on ERT outcomes in Fabry patients collected from 269 studies published through February 2017.
“The aim of the literature review and consensus recommendations of the European panel of experts is to aid in managing patient and physician expectations of treatment outcomes,” researchers wrote.
Most of the studies were conducted in adult male patients with Fabry disease. The data revealed that in this population ERTs can significantly reduce GL-3 accumulation, improving some cardiac outcomes and stabilizing renal function. Also, treatment can improve patients’ quality of life by reducing pain.
Evidence indicated that in adult male patients, treatment is more likely to be beneficial if started before serious organ damage is established and when used at the highest recommended dose (1.0 mg/kg every other week).
For female patients, ERTs’ outcomes were similar to those reported for the male population. In this adult population, ERTs were able to reduce GL-3 accumulation, improve renal manifestations and stabilize renal function. Treatment also improved quality of life in these women, although further evidence is still required to support the finding.
For children and adolescents with Fabry disease, the available literature revealed that ERTs can reduce or normalize GL-3 levels, improve early symptoms of the disease, and potentially change the natural course of the disease and improve quality of life. In this particular group of patients, the ERT dose was an important factor to effectively manage the progression and outcome of the disease.
Supported by the reported variable outcomes, the experts concluded that:
- Fabry disease management should be conducted by multidisciplinary team at all stages of the disease;
- ERT is effective in all patient populations;
- The treatment is most effective if started before established organ damage and when used at an optimal personalized dosing regimen;
- Additional therapies are necessary to improve long-term organ specific outcome, and;
- Medical care plans for Fabry disease should include appropriate, individualized patient therapeutic goals.