Long-term treatment with Cerdelga (eliglustat), a substrate reduction therapy for Gaucher disease type 1, is safe and continuously improves blood parameters, decreases spleen and liver volumes, and reduces markers of disease activity, results from an eight-year study show.
The study, “Outcomes after 8 Years of Eliglustat Therapy for Gaucher Disease Type 1: Final Results from the Phase 2 Trial,” was published in the American Journal of Hematology.
Cerdelga, by Sanofi Genzyme, is designed to decrease the amount of glucosylceramide, a fat molecule that accumulates mainly in the cells of the bone marrow, spleen, and liver of Gaucher patients. As a result, these cells become larger and cause damage to those organs.
The U.S., European Union, and a number of other countries have approved Cerdelga as a long-term treatment for the 90 percent of adults with Gaucher disease type 1 who lack an ultra-rapid CYP2D6 enzyme — a kind of liver enzyme that metabolizes Cerdelga.
Cerdelga has been studied in multiple clinical trials, either in previously untreated patients or in those who had already received enzyme replacement therapy — another treatment approach used for Gaucher disease — and studies have followed patients for as many as 4.5 years.
However, the therapy is intended for lifelong use, and studies examining longer treatment periods are of paramount importance in understanding the long-term safety and effectiveness of the medicine.
Now researchers are reporting the eight-year outcomes of patients who received Cerdelga as a first-line treatment in an open-label Phase 2 trial and extension study (NCT00358150).
“These data represent the longest eliglustat therapy experience to date,” the researchers wrote.
The trial included 26 patients with type 1 Gaucher disease, 19 of whom also completed the extension part — which was designed to last for nine years. Of the seven patients who discontinued the Phase 2 trial, three did so due to adverse events, three because of pregnancy, and one for administrative reasons.
Researchers had already reported that the Phase 2 trial met its primary outcome, with patients seeing improvements in at least two of the three main efficacy measures — spleen volume, hemoglobin level, and platelet count — one year after starting Cerdelga treatment.
Additional analysis showed that blood parameters, spleen and liver volumes, markers of disease activity, and measures of bone health all continued to improve for the first four years.
Investigators now report that these improvements continued or were maintained for the following four years, suggesting that even after eight years, patients kept improving.
“Overall, 100% of patients met the spleen volume goal, 95% met the liver volume and hemoglobin goals, and 63% met the platelet goal,” the researchers wrote.
Patients with more severe disease at enrollment benefited most from Cerdelga, reaching values of spleen and liver volumes, disease activity scores, and blood measures similar to those who had a milder disease at the study’s start.
Patients also experienced improvements in bone health, with no new fractures or bone damage reported throughout the study. Existing lesions also remained stable.
In the first three to four years, patients experienced an increase in their quality of life, and showed reductions in disease activity biomarkers. These measures remained stable for the rest of the trial.
The most common adverse events were abdominal pain, diarrhea, and peripheral nervous system abnormalities, which were reported in two patients each. However, most adverse events (98%) were mild or moderate, and 94% were not related to Cerdelga treatment. Only one patient discontinued treatment due to a tachycardia possibly caused by Cerdelga.
“This is the first trial to show long-term, clinically significant improvements in quality of life and Gaucher disease severity with eliglustat therapy in previously untreated GD1 patients with moderate to severe baseline disease,” the researchers wrote.
“Clinically meaningful improvements in hematologic, visceral, bone, and biomarker parameters were achieved in previously untreated patients with GD1 as early as the first year of treatment with eliglustat. These improvements continued or were maintained over the course of 8 years of eliglustat therapy,” they concluded.
“Quality-of-life measures also showed clinically significant improvements after 8 years of eliglustat. Eliglustat was generally safe and well tolerated with only one withdrawal due to an adverse event considered possibly related to eliglustat,” they added.