Long-term treatment with Cerdelga (eliglustat) safely and consistently lessens or stabilizes disease severity in adults with Gaucher disease type 1 (GD1), according to a six-year study in five patients.
The findings are consistent with results from previous studies, further supporting Cerdelga’s safety and effectiveness in this patient population.
The study, “Case Series Synopsis: Gaucher Disease Type 1 Patients Treated with Eliglustat over 6 Years,” was published in the International Journal of Rare Diseases And Disorders.
GD is caused by a deficient production of beta-glucocerebrosidase, an enzyme responsible for the breakdown of a specific fat molecule called glucocerebroside.
The result is the buildup of glucocerebroside in the liver, spleen, bone, and nervous system, ultimately affecting their function. GD1, the most common form of the disease and the only that typically does not affect the nervous system, may lead to a variety of symptoms, with different severities and ages of onset.
Cerdelga, marketed by Sanofi Genzyme, is an oral substrate reduction therapy that works by blocking the activity of the enzyme that produces glucocerebroside, reducing its accumulation.
The therapy is approved for the long-term treatment of the 90% of adults with GD1 who lack an ultra-rapid CYP2D6 enzyme — a liver enzyme that breaks down Cerdelga.
While Cerdelga’s therapeutic benefits in GD1 patients have been shown in previous clinical trials, reports of long-term treatment are still needed to better understand its long-term safety and effectiveness.
Researchers at the Hospital do Divino Espírito Santo in Portugal assessed the effects of six-year treatment with Cerdelga in five GD1 adult patients, three women and two men.
The patients were diagnosed with GD1 between 26 and 57 years of age, and carried mutations associated with mild disease. Cerldega treatment — 84 mg once or twice daily according to CYP2D6 activity — was initiated in July or August 2011.
Four of the patients had been previously treated with Cerezyme (imiglucerase), an enzyme replacement therapy, for between four and 15 years. Switches from Cerezyme to Cerdelga were mainly associated with Cerdelga’s convenience, since Cerezyme is administrated directly into the vein, which in Portugal requires regular hospital visits.
Three patients had co-morbidities (simultaneous conditions), two of them with type 2 diabetes.
At treatment initiation, disease severity — assessed through the GD-DS3 composite scoring system — was moderate in four patients and mild in one.
All participants had bone marrow involvement — measured using the bone marrow burden (BMB) score — and three showed bone complications with moderate to severe bone pain. Two had mild thrombocytopenia (low levels of platelets), and all showed higher than normal levels of two disease biomarkers, chitotriosidase and ferritin.
Results showed that six years of Cerdelga treatment led to a lessening of disease severity in four patients (80%) and to stabilization in the patient with mild disease. Bone marrow involvement declined (in two patients) or stabilized (in three), and bone or joint pain was considerably eased or eliminated. No bone crises and no new bone complications were reported.
Platelet counts were normalized in the two participants with thrombocytopenia, and all patients showed considerable drops (between 46% and 94%) in the levels of chitotriosidase and ferritin.
None of the patients had bleeds, anemia, or abnormally large spleen or liver — symptoms commonly found in GD1 patients — before or over the six years of treatment.
Cerdelga was well tolerated, with patients reporting mild and transient adverse events, except for a case of persistently mild dry skin.
“Case-study data from six years of oral eliglustat [Cerdelga] treatment in five patients with Gaucher disease type 1 indicates long-term improvements in disease scores, bone measures and biomarkers,” the researchers wrote.
The benefits were consistent with those reported in previous studies, and bone-associated improvements suggested benefits in patients’ quality of life, the researchers said, although quality of life was not directly assessed.
“These data provide useful information on long term treatment trends in type 1 patients treated with oral eliglustat,” they said.
One of the study’s authors received speaking fees and travel funding from Sanofi Genzyme, and participated on advisory boards for the company.
