New data published yesterday in the Orphanet Journal of Rare Diseases
indicate that Elaprase (idursulfase) provides a clinical benefit to mucopolysaccharidosis type II (MPS II; Hunter syndrome) patients.
Hunter syndrome is the result of deficient activity of the enzyme iduronate-2-sulfatase (I2S), and the recent registry study investigated clinical outcomes of a broad population of patients with the disease following ≥ 6 months of enzyme replacement therapy (ERT) with the approved idursulfase.
The recent findings suggest that idursulfase has a clinical benefit on a number of outcome measures, including urinary glycosaminoglycan (uGAG) levels, the 6-minute walk test (6MWT) , left ventricular mass index (LVMI), absolute forced vital capacity (FVC), absolute forced expiratory volume in 1 second (FEV1
), and hepatosplenomegaly.
Hunter syndrome affects approximately 2,000 people worldwide, almost all of whom are young boys. As of January 2016, 1,096 patients were enrolled in the Hunter Outcome Survey (HOS); a large, multicenter, observational registry that collects long-term data on the natural history of the disease and evaluates the safety and efficacy of ERT with idursulfase. Of the enrolled patients, 947 were alive upon entry to the HOS and 639 male patients who had never received a bone marrow transplant and had received idursulfase for ≥6 months and were followed prospectively.
Decreases in uGAG levels were observed in comparison to baseline in the patients receving idulrsulfase and that reduction was maintained for upto 3 years that the patients were followed. Palpable liver and spleen sizes were also reduced in this patient population indicating that idursulfase likely had a positive impact on GAG storage.
Figure 1: Urinary GAG levels
Figure 1 represents the change in uGAG levels. As per the study: “Change in urinary glycosaminoglycan (uGAG) levels. a.
Absolute change and b.
percentage change from baselinea in uGAG levels in patients with data available after 1, 2 or 3 years of treatment with idursulfase. c.
Absolute change and d.
percentage change from baseline in uGAG levels in patients with data available at consecutive time points (year 1, year 2 and year 3 of treatment with idursulfase). Box plots illustrate the 25th, 50th (median) and 75th percentiles (boxes) and the 10th and 90th percentiles (whiskers).”
Measurement of the 6MWT also showed the benefit of the ERT in Hunter syndrome patients. As shown in Figure 2, Median 6MWT distances increased compared with baseline for each year measured. In the 36 patients with 6MWT results at year 3, the median change from baseline was 41.0 meters although a large variance was observed.
Figure 2. 6-Minute Walk Test
Figure 2 displays the data collected from patients who participated in the 6MWT. As per the study: “a
. Baseline distance walked plotted against reference data  by age at assessment (n = 38). b.
Absolute change from baselinea in distance walked in patients with data available after 1, 2 or 3 years of treatment with idursulfase. c.
Percentage change from baseline in distance walked in patients with data available after 1, 2 or 3 years of treatment with idursulfase. Box plots illustrate the 25th, 50th (median) and 75th percentiles (boxes) and the 10th and 90th percentiles (whiskers).”
These real world assessments of the efficacy of ERT in Hunter syndrome are of great value to the community. Even though the data has a large degree of variance, it reflects a tangible population and as such, is just as valuable as the data collected from more controlled, randomized clinical trials.
Muenzer J, Giugliani R, Scarpa M, et al. Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter syndrome survey (HOS). Orphanet J Rare Dis. 2017;12:161. https://doi.org/10.1186/s13023-017-0712-3