"'It has been 20 years since ERT treatments became available for patients with Fabry disease. More treatment options are available to treat Fabry disease, but selecting treatment options and strategy requires precise attention based on research data."

Analysis suggests that the treatment environment for rare diseases has improved due to the emergence of Enzyme Replacement Therapy (ERT) to treat lysosomal storage disease (LSD), such as Fabry disease.

New treatment strategies and research for treatments are being conducted to complement the limitations of ERTs. For example, studies on treatments like Substrate Reduction Therapy (SRT) are being conducted.


However, considering the nature of rare diseases, using available treatment resources to the fullest remains equally important. Antonio Pisani, a professor in the Department of Nephrology at the University of Naples Federico II, has emphasized the importance of monitoring when switching between medicines for treating Fabry disease during a meeting with Daily Pharm.

A study comparing ERT→oral drug switching…disease management through monitoring is essential

During the WORLD Symposium 2024, held in San Diego, USA, in February, a study result was presented that close monitoring for medication switching is essential. It is because after a patient switch from Fabrazyme to oral drugs, a long-term change in treatment outcomes has been reported.

The study is expected to aid in selecting treatments as it compares the efficacy and safety of the ERT treatment, Fabrazyme, to an oral drug, migalastat, using registry data on patients with Fabry disease.

"Migalastat has been approved in Europe in 2016. However, the use of the drug has been limited because there is no real-world evidence (RWE) besides pre-clinical or clinical results," Professor Pisani, who conducted the research, said, "The study analyzed data of patients who had been treated with Fabrazyme over a year and then switched to migalasta and continued treatment over six months. It confirmed various biomarkers for Fabry disease, changes to patient symptoms, whether a patient reached first-line treatment goal and clinical symptoms."

Based on research results, migalastat treatment, compared to Fabrazyme, worsened an estimated glomerular filtration rate (GFR), a biomarker for Fabry disease, and GL-3 level, a glycolipid in cells.

Additionally, a classical-type patient with Fabry disease who switched to migalastat had worsened UPCR and heart index, demonstrating that Fabrazyme is much more effective in treating patients with Fabry disease.

"The study confirmed that migalastat has variability in efficacy in a clinical setting," Professor Pisani said, "We concluded that a close monitoring and patient follow-up is important when a patient has been switched to migalastat following Fabrazyme treatment."

"A close monitoring of enzyme activation and changes to clinical symptoms is necessary. A change in enzyme activation is expected once a patient starts taking migalastat. Therefore, medication switching requires patient follow-up," Professor Pisani emphasized.

Migalastat is approved in South Korea as a long-term treatment for patients over 12 years old diagnosed with Fabry disease with a gene variant. An oral drug can be reimbursed for second-line treatment when a patient has used ERT for over 12 months in a first-line treatment or cannot use ERT.

If the study results were to apply to Korea, what could be the possible analysis? Professor Pisani advises that physicians must carefully consider medication switching based on treatment guidelines for Fabry disease.

"There are studies implicating positive efficacy of migalastat. However, there are opposite results," Professor Pisani said, "When treating with migalastat, physicians must monitor patients by checking biomarkers, such as eGRF and proteinuria, to confirm the efficacy of the use."

Treatment outcomes of migalastat may vary depending on the patient's condition. For example, a classical-type patient with Fabry disease may have a stable or worsened heart-related index upon switching medication to migalastat, but worsening renal functions may accelerate significantly.

"In the end, a follow-up of patients is essential, and it is important to closely monitor symptoms and disease progression of patients with poor baseline indexes," Professor Pisani said.

Still there are limitations to Fabry disease treatment…what are unmet needs?

New Fabry disease treatments are available, and real-world data have been presented. Although these improvements have been made for patients with Fabry disease, there are still unmet needs.

Professor Pisani highly values the benefits brought by ERT treatments to patients with Fabry disease. Yet, he emphasizes the need for new drug development.

Studies being conducted related to new treatment strategies and drugs to complement ERT treatment limitations. For example, studies on substrate reduction therapy and gene therapy are being conducted.

"We can consider possibilities, such as treatment development, including new ERT and chaperone, a combination therapy containing chaperone, or Fabrazyme in combination with gene therapy," Professor Pisani said. "We can approach Fabry disease with new treatments, such as SRT, as it is a lysosomal storage disorder."

Yet, new treatment development takes time. Therefore, a strategic approach is necessary using known research results.

"There are several possibilities for Fabry disease treatment. Physicians should now plan treatment option selection and strategy using research data," Professor Pisani said. "The dosage of treatment is an important factor for Fabry disease. A sufficient dosage administration can delay the disease progression."

"I would like to emphasize the importance of early treatment through early diagnosis. Early treatment can delay the disease progression and worsening," Professor Pisani emphasizes.