Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

Summary

Primary Objective: The primary objective of this phase 2/3 study was to evaluate the efficacy of olipudase alfa (recombinant human acid sphingomyelinase) administered intravenously once every 2 weeks for 52 weeks in adult participants with acid sphingomyelinase deficiency (ASMD) by assessing changes in: 1) spleen volume as measured by abdominal magnetic resonance imaging (MRI) (and, for the United States \[US\] only, in association with participant perception related to spleen volume as measured by splenomegaly-related score \[SRS\]); and 2) infiltrative lung disease as measured by the pulmonary function test, diffusing capacity of the lung for carbon monoxide (DLCO). Secondary Objectives: * To confirm the safety of olipudase alfa administered intravenously once every 2 weeks for 52 weeks. * To characterize the effect of olipudase alfa on the participant perception related to spleen volume as measured by the SRS after 52 weeks of study drug administration. (For the US, the effect of olipudase alfa on the SRS is part of the primary objective). * To characterize the effect of olipudase alfa after 52 weeks of study drug administration on the following outcome measures assessed sequentially: * The effect of olipudase alfa on liver volume; * The effect of olipudase alfa on platelet count; * The effect of olipudase alfa on fatigue; * The effect of olipudase alfa on pain; * The effect of olipudase alfa on dyspnea.

Timeline

Start

2015-12-18

Primary completion

2021-03-15

Completion

2023-10-19

Outcome

Mixed primary results

registry analysis (superiority test); Placebo vs Olipudase Alfa; p =0.0004; Least Squares Mean Difference 19.008 (95% CI 9.319 to 28.696); NCT02004691 ↗

registry analysis (superiority test); Placebo vs Olipudase Alfa; p <.0001; Least Squares Mean Difference -39.927 (95% CI -47.051 to -32.803); NCT02004691 ↗

registry analysis (superiority test); Placebo vs Olipudase Alfa; p =0.6364; Least Squares Mean Difference 1.618 (95% CI -5.302 to 8.538); NCT02004691 ↗

release “In the primary analysis period (52 weeks), the first independent primary endpoint, DLco, was met; therefore, ASCEND was declared positive.” sanofi.com ↗

release “Compared to baseline, the SRS improved to a similar extent in both the olipudase alfa and placebo arms; therefore, this combination endpoint was not met.” sanofi.com ↗

Publications

• Wasserstein MP, Lachmann R, Hollak C, Barbato A, Gallagher RC, Giugliani R, Guelbert NB, Hennermann JB, Ikezoe T, Lidove O, Mabe P, Mengel E, Scarpa M, Senates E, Tchan M, Villarrubia J, Thurberg BL, Yarramaneni A, Armstrong NM, Kim Y, Kumar M. Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial. Orphanet J Rare Dis. 2023 Dec 2;18(1):378. doi: 10.1186/s13023-023-02983-0.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Olipudase alfa	Protein / enzyme biologic	3 mg/kg	Intravenous

Indications