Cerdelga (eliglustat) safely and effectively treated three adults with Gaucher disease type 1 (GD1), who switched from long-term use of enzyme replacement therapy (ERT) to this substrate reduction therapy (SRT), a study from Korea reports.
The study, “One-year experience of oral substrate reduction therapy in three patients with Gaucher disease type I,” was published in the Journal of Genetic Medicine.
GD1 is caused by a functional lack of the enzyme beta-glucocerebrosidase. Normally, this enzyme helps to break down a molecule called glucocerebroside; when defective, glucocerebroside accumulates in the body, with toxic effects.
For many years, the standard care for GD1 has been ERT — as the name suggests, this type of treatment involves administering the missing beta-glucocerebrosidase enzyme. However, ERTs typically require regular infusions, which can be burdensome to patients.
Cerdelga, by Sanofi Genzyme, is an oral capsule substrate reduction therapy. As such, it works to slow the body’s production of glucocerebroside, limiting the toxic buildup of this molecule. The safety and efficacy of Cerdelga as a GD1 treatment have been demonstrated in clinical trials, and it is approved for these patients in the U.S. and Europe. It was approved for GD1 patients in Korea in 2018.
Researchers at Ajou University School of Medicine, in Suwon, reported on three patients from two families who switched from long-term ERT use to Cerdelga.
The first, a 43-year-old woman, was diagnosed with GD1 at age 11 and started on Cerezyme (imiglucerase, also by Sanofi), an ERT, 10 years later. She was stable with Cerezyme for over 20 years, becoming pregnant and giving birth at 39.
At age 41, the woman decided to switch to Cerdelga. This decision was due to the burden of regular infusions and lower compliance. Her medical condition remained stable during treatment, with mild side effects (headache and indigestion).
But after a year on Cerdelga, she developed an acute viral illness. Physicians at local clinics declined to prescribe medications for the infection, owing to concerns over possible adverse interactions between the therapies. The viral illness caused nausea, abdominal discomfort, and skin rashes that made her skip Cerdelga doses.
Although she recovered from the infection, the patient decided to switch back to ERT after this episode.
The second patient, a 41-year-old man, is this woman’s younger sibling. He was diagnosed with GD1 at age 18, and started on Cerezyme at age 20. Similar to his sister, this patient was successfully treated with ERT for over two decades, then decided to switch to Cerdelga.
He had been treated with Cerdelga for a year when this study concluded, without any notable side effects. A few months into treatment, laboratory measures — particularly lyso-Gb1, a GD biomarker — changed in concerning ways. Those changes were attributed to a lack of adherence, as the patient was not taking the medication as prescribed. After he was given some additional education and started taking the medicine as directed, these measures returned to normal.
The third patient, a 31-year-old man, was diagnosed with GD at age 2 and started on an ERT at age 9. Again, clinical and laboratory parameters were stable with ERT treatment for over two decades, with the patient being able to graduate university and get a job.
But he was unable to get ERT infusions as often as needed, and the decision was made to switch to oral Cerdelga. After one year on therapy, his condition remained stable, without notable adverse effects.
“This study described the one-year experience of eliglustat [Cerdelga] therapy in three adult patients with GD1 who were clinically stabilized by over 20-year ERT. Although more long-term data is needed, eliglustat therapy was generally tolerated and the clinical parameters were remained stable,” the researchers concluded.
