FDA approves Xenpozyme for acid sphingomyelinase deficiency.

The approval is based on positive data from the ASCEND and ASCEND-Peds clinical trials, in which Xenpozyme showed clinically relevant improvement in lung function (as measured by diffusing capacity of the lung for carbon monoxide, or DLco) and platelet count, and reduction of spleen and liver volumes, with a demonstrated safety profile. The ASCEND trial evaluated the efficacy and safety of Xenpozyme; 31 adult patients with ASMD type A/B or type B were randomized to receive Xenpozyme or placebo for 52 weeks (primary analysis). In the trial, Xenpozyme improved lung function, assessed as the percent change from baseline to Week 52 in predicted diffusing capacity of the lung for carbon monoxide (DLco), and reduced spleen volume, evaluated as percent change from baseline in multiples of normal (MN). Twelve (12) patients treated with Xenpozyme had a mean change in percent predicted DLco from baseline (49.1%) to Week 52 (59.4%). This change represents a 23.9% relative improvement compared to a 3% improvement in DLco from baseline in the 17 patients from the placebo group (48.5%) to Week 52 (49.9%). The difference between the two arms (20.9%) was nominally statistically significant (p=0.0003). Thirteen (13) patients treated with Xenpozyme had a mean reduction in spleen volume by 38.9% from baseline (11.5 MN) to Week 52 (7.2 MN) compared to a mean increase by 0.5% for the 17 patients in the placebo group from baseline (11.2 MN) to Week 52 (11.2 MN). The difference between the two arms (39.4%) was nominally statistically significant (p<0.0001). twelve (12) patients treated with xenpozyme had a mean reduction in liver volume by 26.5% from baseline (1.4 mn) to week 52 (1.0 mn) compared to a mean decrease of 1.8% for the 17 patients in the placebo group from baseline (1.6 mn) to week 52 (1.6 mn). the difference between the two arms (24.7%) was nominally statistically significant (p><0.0001). thirteen (13) patients treated with xenpozyme had a mean improvement in platelet count by 18.3% from baseline (109.3x109 l) to week 52 (126.4x109 l) compared to increase by 2.7% for the 16 patients in the placebo group from baseline (115.6x109 l) to week 52 (120.2x109 l). the difference between the two arms (15.6%) was nominally statistically significant (p="0.0280)."

All ASCEND patients treated with Xenpozyme showed improvement in key endpoints (DLco and spleen and liver volume). Most frequently reported adverse drug reactions in adults (incidence at least 10%) were headache, cough, diarrhea, hypotension, and ocular hyperemia. The single-arm ASCEND-Peds trial studied 8 pediatric patients younger than 12 years of age with ASMD type A/B or type B who all received Xenpozyme, with a primary objective of evaluating the safety and tolerability of Xenpozyme for 64 weeks. All patients completed the study and continued in an extension trial. The ASCEND-Peds trial also explored efficacy endpoints of progressive lung disease, spleen and liver enlargement, and platelet count.