AstraZeneca’s rare-disease unit Alexion has secured a Priority Review from the US Food and Drug Administration for efzimfotase alfa, an investigational treatment for patients aged two years and older with hypophosphatasia (HPP).

 

The FDA has accepted Alexion’s Biologics License Application (BLA), setting the stage for a regulatory decision expected in the first half of 2027 under the Prescription Drug User Fee Act timeline.

 

If approved, efzimfotase alfa would be the first treatment intended to address both skeletal abnormalities and functional impairments across patients with HPP, regardless of when the disease begins. The drug is designed for subcutaneous administration once every two weeks.

 

“Today’s Priority Review marks an important step forward for the HPP community and reinforces the potential for efzimfotase alfa to redefine treatment outcomes. Building on Alexion’s pioneering legacy in HPP and shaped by patient insights, efzimfotase alfa was designed to address the skeletal and functional manifestations of this rare metabolic disease, with the convenience of self-administration every two weeks and five times lower annualised rates of injection site reactions compared to Strensiq," said Marc Dunoyer, Chief Executive Officer, Alexion.

 

The application is backed by data from what Alexion describes as the largest Phase III clinical programme in HPP. The programme comprises three trials — HICKORY, MULBERRY and CHESTNUT — covering adolescents, adults and children, including patients who had previously received Strensiq (asfotase alfa).

 

HPP is a rare inherited metabolic disorder caused by deficient activity of alkaline phosphatase (ALP), an enzyme involved in healthy bone mineralisation and muscle function. The disease can cause defective bone mineralisation, disrupted calcium and phosphate regulation, muscle weakness, neurological symptoms, fatigue and pain.

 

The MULBERRY trial evaluated efzimfotase alfa in 29 children aged two to under 12 who had not previously been treated with Strensiq. Patients received either efzimfotase alfa or placebo every two weeks for 24 weeks, with researchers assessing changes in skeletal health and physical function.

 

The CHESTNUT trial involved 43 children aged two to under 12 who had already received Strensiq for at least six months. Participants were assigned to efzimfotase alfa or continued Strensiq treatment, with safety and tolerability as the primary focus alongside measures of skeletal health.

 

HICKORY enrolled 124 adolescents and adults aged 12 and older who had not previously received Strensiq. The trial assessed efzimfotase alfa against placebo, with the primary endpoint focused on changes in walking ability measured by the Six-Minute Walk Test. Secondary measures included physical function, pain, fatigue, quality of life and safety.

 

Alexion said efzimfotase alfa demonstrated a favourable safety profile and was generally well tolerated across all three Phase III trials.