FDA grants priority review to efzimfotase alfa for hypophosphatasia in patients aged 2 years and older

The FDA has accepted a biologics license application (BLA) for efzimfotase alfa, an investigational enzyme replacement therapy for hypophosphatasia (HPP), and granted it priority review for patients aged 2 years and older, Alexion, AstraZeneca Rare Disease, announced on September 18, 2026.¹ The FDA's action date is anticipated in the first half of 2027.¹

“Today’s Priority Review marks an important step forward for the HPP community and reinforces the potential for efzimfotase alfa to redefine treatment outcomes,” said Marc Dunoyer, CEO of Alexion. “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 2 weeks and five times lower annualised rates of injection site reactions compared to Strensiq.”

Efzimfotase alfa phase 3 trial design and efficacy in pediatric HPP

MULBERRY randomized 29 treatment-naive children aged 2 to younger than 12 years with HPP-related rickets 2:1 to weight-based efzimfotase alfa dosing or placebo, given subcutaneously every 2 weeks for 24 weeks.¹ The primary endpoint was Radiographic Global Impression of Change (RGI-C) at day 169; secondary endpoints included Rickets Severity Score (RSS), 6-minute walk test, and motor proficiency measures.¹ At week 25, the observed median RGI-C score was 1.67 with efzimfotase alfa vs 0 with placebo (median difference, 1.67; 95% CI, 0.66-2.00).³ The company reported a significant RSS improvement and supportive physical function findings but disclosed no effect sizes for them.^2,3

CHESTNUT randomized 43 children previously treated with asfotase alfa for at least 6 months 1:1 to efzimfotase alfa every 2 weeks or continued asfotase alfa for 24 weeks, with treatment-emergent adverse events as the primary endpoint.¹ Efzimfotase alfa was reported as well tolerated and maintained bone health by RGI-C and RSS at week 25.²

“Underlying alkaline phosphatase deficiency in HPP can lead to severe, progressive bone, neurological, and functional symptoms in children with detrimental impact to physical and social-emotional wellbeing during a critical stage of development,” said Jill Simmons, MD, director of the Program for Pediatric Metabolic Bone Disorders at Vanderbilt Health, interim director of Pediatric Endocrinology and Professor of Pediatric Endocrinology at Vanderbilt University and principal investigator for the CHESTNUT trial. “These positive results, including a statistically significant improvement in bone health and meaningful benefit in physical function, represent a clinically important advancement for children living with this lifelong disease.”

Hypophosphatasia burden and asfotase alfa as current standard of care

HPP is a rare, inherited metabolic disease caused by deficient alkaline phosphatase activity, marked by defective bone mineralization, impaired calcium and phosphate regulation, and functional impairments such as muscle weakness, pain, and fatigue.¹ Diagnosed prevalence in the US was estimated at 2.8 per 100,000, and about 80% of people with HPP are adults.² Asfotase alfa is FDA-approved for perinatal/infantile- and juvenile-onset HPP, dosed at 6 mg/kg weekly as either 3 or 6 subcutaneous injections, and its label notes that injection site reactions may limit tolerability of the 6-times-weekly schedule.⁴

Efzimfotase alfa mechanism and regulatory status

Efzimfotase alfa replaces the deficient alkaline phosphatase activity that underlies HPP and is being developed for subcutaneous dosing every 2 weeks.¹ It has no approved indications. Submissions are also under review in Japan and other markets.¹ Priority review is reserved for therapies that, if approved, would offer significant improvements in safety or efficacy over available options.¹ It signals the agency's expedited timeline, not a conclusion about efficacy.

“The efzimfotase alfa phase 3 clinical programme represents the largest and most diverse investigation of HPP to date, spanning a broad patient population with a wide range of disease manifestations,” said Gianluca Pirozzi, senior vice president, Head of Development, Regulatory and Safety, Alexion, AstraZeneca Rare Disease. “By addressing the root cause of HPP, alkaline phosphatase deficiency, efzimfotase alfa has the potential to meaningfully improve outcomes with a convenient, self-administered option for the HPP patient community.”

References

1. Alexion, AstraZeneca Rare Disease. Efzimfotase alfa granted Priority Review in the US as treatment for patients with hypophosphatasia aged 2 years and older. Press release. September 18, 2026. Accessed September 18, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/efzimfotase-alfa-granted-priority-review-us-as-treatment-for-patients-with-hypophosphatasia-aged-2-years-and-older.html

2. AstraZeneca. Efzimfotase alfa demonstrated positive results from global phase III clinical programme in hypophosphatasia. Press release. March 31, 2026. Accessed September 18, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/efzimfotase-alfa-demonstrated-positive-results-global-phase-iii-clinical-programme-hypophosphatasia.html

3. AstraZeneca. Efzimfotase alfa demonstrated improvements in bone health in treatment-naive paediatric patients with hypophosphatasia achieving median difference of 1.67 vs placebo in RGI-C score at week 25 in MULBERRY phase III trial. Press release. June 2026. Accessed September 18, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/efzimfotase-alfa-demonstrated-improvements-in-bone-health-in-treatment-naive-patients-with-hypophosphatasia-at-week-25-in-mulberry-phase-iii-trial.html

4. Strensiq (asfotase alfa). Prescribing information. Alexion Pharmaceuticals; 2024. Accessed September 18, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125513s033lbl.pdf