Eliglustat: Replacing Enzyme Replacement Therapy for Patients With Gaucher Disease Type 1?

Author’s Perspective

Lead author Timothy M. Cox, MD: “In this trial of nearly 400 patients with more than 500 patient-years of follow-up [of eliglustat] was safe, tolerable, and resulted in good quality of life. I’ve looked after patients with Gaucher disease for 25 years. Enzyme infusions are effective, but giving infusions – even every two weeks – is quite invasive and expensive. To have an oral therapy like eliglustat that is dosed twice (or, in some cases, once) a day is incredibly liberating for patients. … These trials were conducted with the commitment to investigate the drug for children with Gaucher disease, who tend to have quite severe disease; we are now looking to expand the opportunities for children and to have eliglustat as an option.


The randomized, multinational, open-label, phase III ENCORE study found that eliglustat (a substrate reduction therapy) was noninferior to imiglucerase (enzyme replacement therapy [ERT]) as maintenance therapy for patients with Gaucher disease type 1 who were already stabilized with ERT. After the initial one-year analysis, patients were invited to stay on the study for up to four years, and, according to a report published in Blood, eliglustat remained safe and efficacious during long-term follow-up.

Timothy M. Cox, MD, of the University of Cambridge in the United Kingdom, and co-authors analyzed data from 157 patients enrolled in the ENCORE study between September 2009 and November 2011, in which patients were randomized to receive eliglustat 50, 100, or 150 mg twice daily. During follow-up (with a data cutoff of May 2015), 148 patients completed one year of therapy, 139 completed two years, 115 completed three years, and 46 completed four years.

Mean values for hemoglobin concentration, platelet count, spleen volume, and liver volume remained stable among patients receiving eliglustat, both collectively (the study’s primary endpoint; ≥85%) and individually (secondary endpoint; ≥92%). There were small but statistically significant reductions in mean liver volumes (3%; p=0.02) and spleen volumes (13%; p<0.001) in patients who received four years of eliglustat treatment.

Mean baseline bone mineral density scores were also maintained throughout four years of treatment; after four years, lumbar spine least-square mean Z-scores increased by 0.29 (p<0.0001). However, the authors noted that active bone disease was an exclusion criterion for the study, so these results “do not address the question of whether eliglustat can reverse preexisting bone disease.” Three patients (2%) reported a bone crisis during treatment, including one patient who had a bone crisis at baseline.

Of the 141 patients who responded to a treatment preference survey, 98 percent expressed a preference for oral therapy, as it was deemed the most convenient option. The authors observed “good” long-term compliance, with 96 percent of patients taking at least 80 percent of their medication.

The authors also considered the treatment to be “well tolerated,” with no new safety concerns reported. Seventy-four percent of adverse events (AEs) were mild, 23 percent were moderate, and 3 percent were severe. The most common AEs were upper abdominal pain (n=11; 7%), arthralgia (n=9; 6%), dyspepsia (n=9; 6%), fatigue (n=8; 5%), gastritis (n=8; 5%), diarrhea (n=8; 5%), and abnormal nerve conduction (n=8; 5%). Four patients (2.5%) withdrew from the study because of AEs.

The study’s findings are limited by the small proportion of patients who received eliglustat for the full four years. The study also lacked a comparator group, “thus no direct comparison can be made over this period with patients who continue to receive long-term enzyme therapy,” the authors noted.

Source: Cox TM, Drelichman G, Cravo R, et al. Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy. Blood. 2017 February 6. [Epub ahead of print]

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