AstraZeneca has shared the data behind previously disclosed phase 3 rare disease wins, fleshing out the case for a Strensiq successor tipped to generate blockbuster sales. The company has yet to share data from a third trial that missed its primary endpoint.
In March, AstraZeneca reported that its investigational enzyme replacement therapy efzimfotase alfa beat placebo in a phase 3 study of treatment-naive children with hypophosphatasia (HPP), a condition that affects bone development. The victory in that trial, Mulberry, was supported by data from another study, Chestnut, which switched patients from AstraZeneca’s Strensiq to efzimfotase alfa.
AstraZeneca shared Mulberry and Chestnut data on Sunday at the International Conference on Children’s Bone Health. At Week 25 of Mulberry, patients on efzimfotase alfa had a median Radiographic Global Impression of Change (RGI-C) score of 1.67, compared to 0 on placebo. RGI-C measures skeletal health.
A secondary Mulberry endpoint linked efzimfotase alfa to a median reduction in a radiographic assessment of the Rickets Severity Score (RSS) of 1 at Week 25, compared to 0 on placebo. People with rickets, a condition associated with HPP, have weak and soft bones. AstraZeneca also reported a nominally significant improvement in physical function and a numeric Six-Minute Walk Test (6MWT) improvement.
Comparing the Mulberry results to data on Strensiq is complicated by differences in trial designs. While Mulberry enrolled children aged two to 12 years, Strensiq’s use in juvenile-onset HPP is supported (PDF) by a trial that enrolled people aged six to 12 years. Alexion, AstraZeneca’s rare disease unit, enrolled people aged three weeks to 39.5 months to support use in perinatal and infantile-onset HPP.
In Chestnut, the incidence of treatment-emergent adverse events at Week 25 was similar in people who switched to efzimfotase alfa, 90.5%, and who stayed on Strensiq, 86.4%. Bone health was maintained in children who switched to efzimfotase alfa with RGI-C of 0 in both cohorts. RSS was 0 in the efzimfotase alfa arm and -0.08 in the Strensiq group.
Patients may prefer efzimfotase alfa to Strensiq if the investigational therapy matches the efficacy, safety and tolerability of the incumbent drug. Patients in Mulberry received the study drug subcutaneously every two weeks. Strensiq is administered subcutaneously three or six times a week, depending on the dose.
AstraZeneca designed the phase 3 program to establish efzimfotase alfa in a broader patient population than Strensiq. The failure of a phase 3 trial, Hickory, in people 12 years and older with HPP who hadn’t previously received Strensiq raised doubts about the expansion plan. Yet while the study drug performed no better than placebo on the 6MWT, AstraZeneca argued that other data support use in older patients.
“The results show clinically meaningful impact on mobility, physical function, pain and fatigue that are key aspects of this heterogeneous disease that are beyond one single endpoint such as the 6-minute walk test, the only approved adult endpoint,” Alexion CEO Marc Dunoyer said on an earnings call in April.
Dunoyer reiterated the belief that efzimfotase alfa can generate peak sales of $3 billion to $5 billion. AstraZeneca reported Strensiq sales of $1.7 billion last year.
The company will share data from Hickory, a key plank of its market-expansion plan, at an upcoming medical meeting.
