Patients with type 1 Gaucher disease being treated with VPRIV (velaglucerase alfa) can safely transition to Cerdelga (eliglustat) or Cerezyme (imiglucerase) and maintain clinical stability, according to a new study that draws on data from the ENCORE trial.
The study, “Stability Is Maintained In Adults With Gaucher Disease Type 1 Switched From Velaglucerase Alfa To Eliglustat Or Imiglucerase: A Sub-Analysis Of The Eliglustat ENCORE Trial,” was published in the journal Molecular Genetics and Metabolism Reports.
Gaucher disease is caused by a deficiency in the enzyme acid β-glucosidase, which results in the accumulation a lipid called glucosylceramide. There are currently two types of treatment approaches: intravenous enzyme therapy (in which patients receive copies of functional acid β-glucosidase), or oral substrate reduction therapy (patients receive an inhibitor of glucosylceramide production in order to slow its toxic accumulation).
Three enzyme therapies are available to Gaucher type 1: Cerezyme, VPRIV, and Elelyso (taliglucerase alfa). Substrate reduction therapies include Zavesca (miglustat) and Cerdelga. While Cerezyme is the standard treatment for enzyme therapy, Cerdelga is the first-in-line treatment for substrate reduction in type 1 patients.
“With up to five therapeutic options for Gaucher disease, it is important for clinicians to understand the potential implications of switching from one treatment to another,” the authors wrote. Previous analyses had assessed the outcome of switching from one therapy to another, but the Phase 3 ENCORE trial (NCT00943111) was the first to study the effect of switching from either Cerezyme or VPRIV enzyme therapies to substrate reduction therapy with Cerdelga.
The trial followed 159 adults with confirmed acid β-glucosidase deficiency, who had achieved the following therapeutic goals after at least three years of treatment with either Cerezyme or VPRIV:
- hemoglobin concentration of at least 11g/dL (women) or at least 12 g/dL (men);
- platelet count above or equal to 100 × 109/L
- spleen volume below 10 multiples of normal (MN)
- liver volume below 1.5 MN
- no bone crisis or symptomatic bone disease within the last year.
Patients were divided according to their previous enzyme therapy dose (less than 35 units/kg/2 weeks, or at least 35 units/kg/2 weeks) and received either oral Cerdelga (n = 106) or Cerezyme infusions (n = 53) for one year. The primary analysis revealed that Cerdelga was not inferior to Cerezyme in maintaining clinical stability in previously stabilized adult Gaucher patient (at least 3 years of enzyme therapy).
Researchers also focused on the subgroup of 30 patients, who were initially treated with VPRIV and who, during the study, switched to Cerdelga (22) or Cerezyme (8).
“Efficacy and safety in [VPRIV]-transitioned patients were consistent with the full ENCORE trial population; 90% of patients [who] switched to [Cerdelga] and 88% of patients [who] switched to [Cerezyme] met the composite endpoint (stable hemoglobin concentration, platelet count, spleen volume, and liver volume),” they wrote. “Clinical stability was maintained for 12 months in Gaucher disease type 1 patients in the ENCORE trial who switched from [VPRIV] to either [Cerdelga] or [Cerezyme].”
The frequency and severity of adverse events in the patients who switch from VPRIV were also consistent with those reported in the full trial population. For instance, the 22 patients who received Cerdelga reported diarrhea, fatigue, headache, pain in extremity, palpitations, and throat irritation. Each symptom occurred in two patients (9 percent).