Phase II/III ASCEND study of GZ 402665 meets first endpoint in Niemann-Pick Disease.- Sanofi

GZ 402665 (olipudase alfa), an investigational recombinant human acid sphingomyelinase from Sanofi, demonstrated positive results in a phase II/III clinical trial evaluating olipudase alfa for the treatment of acid sphingomyelinase deficiency (ASMD) or Niemann-Pick Disease (NPD) Type A and Type B, in adult patients. The randomized Phase II/III ASCEND trial enrolled 36 adult patients with ASMD across 24 centers in 16 countries. The trial contained two independent primary efficacy endpoints to address separate critical manifestations of ASMD, progressive lung disease and enlarged spleen, which are prominent clinical features in patients with ASMD. The first independent primary endpoint measuring improvement in lung function, using the percent predicted diffusing capacity of carbon monoxide (DLco), was met; therefore, ASCEND is declared positive. The relative improvement from baseline to week 52 was 22% for the olipudase alfa arm compared with 3% for the placebo arm. The difference between the two treatment arms (19%) was statistically significant (p=0.0004). The other independent primary endpoint measuring the effect of olipudase alfa on spleen size, assessed as percent change from baseline in multiples of normal (MN) of spleen volume, was met per the study protocol. In the olipudase alfa arm, spleen volume was reduced by 39.5%, compared with a 0.5% increase in the placebo arm. The difference between the two treatment arms (40%) was statistically significant (p<0.0001). for the u.s., the spleen volume endpoint was further combined with a patient-reported outcome (pro) measurement of symptoms associated with enlarged spleen called splenomegaly related score (srs). compared to baseline, the srs was reduced by 8.0 points in the olipudase alfa arm and 9.3 points in the placebo arm (p="0.70);" therefore, this combination endpoint was not met. over the 52-week period, all patients in both the placebo and olipudase alfa arms experienced at least one adverse event. the number of events was lower in the olipudase alfa arm (242 events) compared with the placebo arm (267 events). severe adverse events were less frequent in the olipudase alfa arm (3 events) compared with the placebo arm (13 events). there were five serious adverse events in the olipudase alfa arm and 11 in the placebo arm, none of which were treatment related. there were no adverse events that led to treatment discontinuation or study withdrawal. the most common adverse events (as defined by percentages of events greater than or equal to 2% and number of patients greater than or equal to two in all olipudase alfa treated patients; occurring with higher percentages in olipudase alfa patients compared to placebo patients) seen in this trial were headache, nasopharyngitis, upper respiratory tract infection, cough, and arthralgia.>