Elelyso yields long-term benefits in type 1 Gaucher: Real-world study
Patients on enzyme replacement therapy had stable or improved outcomes
Elelyso (taliglucerase alfa) provides long-term clinical benefits for people with type 1 Gaucher disease, with a favorable safety profile, according to real-world data from a 10-year study in Albania.
The treatment was effective in both patients starting therapy for the first time and in those who switched from Cerezyme (imiglucerase), another enzyme replacement therapy (ERT). Participants experienced stable or improved clinical outcomes.
The study, “Ten-Year Follow-Up of Taliglucerase Alfa in Type 1 Gaucher Disease: Real-World Evidence from Albania,” was published in the Journal of Clinical Medicine.
ERT is standard Gaucher type 1 treatment
Gaucher disease is caused by mutations in the GBA1 gene, resulting in a missing or defective glucocerebrosidase (GCase), the enzyme responsible for breaking down the fatty molecule glucocerebroside (Gb3).
The lack of a functional GCase results in the accumulation of these fatty molecules inside cells, leading to disease symptoms such as an enlarged spleen and liver, low levels of immune cells, and bone problems.
ERT is the standard treatment for Gaucher disease type 1, a form of the disease that does not cause neurological symptoms. The therapy works by supplying the body with a functional version of GCase, essentially replacing the defective enzyme to restore the normal breakdown of Gb1.
While the approach has significantly improved patient prognosis, there’s still limited real-world data supporting the long-term benefits of Elelyso, especially in populations with unique genetics.
To learn more, researchers in Albania evaluated the long-term safety and efficacy of Elelyso in individuals with Gaucher type 1 who received the medication for at least one year between 2015 and 2024.
Out of a total of 29 patients, 13 were treatment-naïve, meaning they had not yet received other Gaucher disease treatments. These patients experienced their first symptoms at a mean age of 26.9 years, and their mean age at diagnosis was 36.2 years, resulting in an average diagnostic delay of 9.3 years.
The remaining 16 had previously been on Cerezyme. They were diagnosed at a mean age of 13.7 years, about three years after the onset of symptoms.
“The significant delay observed in treatment-naïve patients is likely related to the milder clinical manifestations in this group,” the researchers wrote.
Hemoglobin, platelet levels improved, remained stable with Elelyso treatment
The majority of patients in both groups (65.5%) carried the p.[Asn409Ser] mutation in one copy of the GBA1 gene and the [His255Gln;Asp448His] mutation in the other copy, a combination that has been reported almost exclusively in Albanian and neighboring populations.
At the start of treatment, the most common symptoms included an enlarged spleen (82.8%), an enlarged liver (44.8%), low levels of platelets (37.9%), and bone pain (24.1%). Platelets are cellular fragments that help the blood to clot.
Compared with switched patients, treatment-naïve patients had lower levels of hemoglobin (the protein that carries oxygen in red blood cells) and platelets, as well as larger liver and spleen volumes.
Over the course of up to 10 years of treatment with Elelyso, hemoglobin and platelet levels improved or remained stable in both groups. Liver size progressively normalized over time, and spleen volume was also significantly decreased, although it remained approximately 3 to 4 times higher than normal after 10 years.
These findings support [Elelyso] as a reliable long-term therapeutic option for patients with [Gaucher disease type 1].
The researchers also found that levels of glucosylsphingosine (lyso-Gb1), a molecule produced from Gb1 that accumulates in people with Gaucher, fell by 86.1% over 10 years among treatment-naïve patients.
Those who switched first experienced an increase in this biomarker at five years due to therapy interruption, but levels eventually declined by 37% at 10 years.
“These findings reinforce lyso-Gb1’s sensitivity to treatment continuity and highlight its potential utility in monitoring compliance and therapeutic efficacy,” the researchers wrote. The data also reveal that “monitoring lyso-Gb1 enables the early detection of absent or insufficient treatment before clinical consequences arise.”
Bone mineral density, a measure of bone strength, was also normalized in both groups after five years. However, four patients in each group still had low mineral density after treatment, which the researchers said is “consistent with existing data indicating that the treatment of bone disease with enzyme replacement therapy remains a clinical challenge.”
The most common side effects included hives, itching, and lip swelling. Antibodies targeting Elelyso, which may compromise its efficacy, were reported in two patients, but only one exhibited a reduced treatment response.
“These findings support [Elelyso] as a reliable long-term therapeutic option for patients with [Gaucher disease type 1],” the researchers wrote.
