Sanofi's rare disease drug hits endpoint, teeing up 2021 filing

Sanofi global R&D head John Reed
Sanofi's head of global R&D John Reed (Sanofi)

Sanofi’s olipudase alfa has improved outcomes in patients with a rare genetic disease. The primary endpoint success in a phase 2/3 trial, coupled with midphase pediatric results, sets Sanofi up to file for approval in acid sphingomyelinase deficiency (ASMD) next year.

ASMD, also known as Niemann-Pick disease type A and type B, is an autosomal recessive lysosomal storage disorder that stems from mutations in the gene that encodes for sphingomyelinase. In the absence of normal levels of the enzyme, a type of lipid called sphingomyelin accumulates in cells. The accumulation leads to cell death and the malfunctioning of organs.

Sanofi designed olipudase alfa, a recombinant human ASM, to stop that deterioration by ensuring patients have enough of the enzyme to gradually reduce levels of sphingomyelin. The results shared today validate that hypothesis.

In a 36-subject phase 2/3 trial, adults randomized to receive infusions of olipudase alfa every two weeks for a year experienced a 22% improvement from baseline in a measure of lung function. The placebo cohort experienced a 3% improvement, resulting in the clinical trial meeting the first of its two independent primary endpoints.

The second independent primary endpoint assessed spleen volume. The spleen volumes of patients on olipudase alfa fell by 39.5% over the course of the clinical trial, compared to a 0.5% increase in the control group. That resulted in a statistically significant difference between the two arms.

Those figures compare favorably to the results of a phase 1 clinical trial, in which Sanofi linked the enzyme replacement therapy to a 23% fall in spleen volume and 24% improvement in lung function. 

In the phase 2/3, Sanofi missed another endpoint that combined the spleen volume endpoint with a patient-reported outcome that assessed symptoms associated with an enlarged spleen. However, the overall picture is positive for Sanofi, with the total lack of treatment-related serious adverse events adding to the upbeat readout.

The safety profile seen in a phase 2 trial of 20 pediatric patients is somewhat muddier. Three patients experienced five treatment-related serious adverse events between them. One patient suffered from two cases of transient, asymptomatic elevation of an enzyme found in the liver and kidneys. Another patient came out in hives and a rash. A third subject experienced a “severe and serious” anaphylactic reaction. No adverse events led to the permanent discontinuation of a patient from the trial. 

With the secondary endpoints tracked by the phase 2 identifying signs of efficacy, including a 49% reduction in spleen volume, Sanofi thinks it is on track to bring olipudase alfa to market. However, a filing is still some way off, with Sanofi penciling in a submission for the second half of 2021. 

Sanofi expects olipudase alfa to become the first approved treatment for ASMD, which it estimates affects around 2,000 people in the U.S., Europe and Japan. According to Sanofi, around 3% of people with the disease die annually due to respiratory or liver failure.