FDA Grants Priority Review to Efzimfotase Alfa BLA for Hypophosphatasia

Alexion, AstraZeneca Rare Disease’s Biologics License Application (BLA) for investigational efzimfotase alfa (ALXN1850) has been accepted and granted Priority Review by the US Food and Drug Administration (FDA) for patients aged 2 years and older with hypophosphatasia (HPP). The FDA action advances the therapy toward a regulatory decision expected in the first half of 2027, according to AstraZeneca.

Efzimfotase Alfa Targets the Underlying Enzyme Deficiency

HPP is a rare inherited metabolic disorder caused by deficient activity of alkaline phosphatase (ALP), an enzyme required for normal bone mineralization and calcium and phosphate regulation. The resulting abnormalities can affect the skeleton and produce muscle weakness, pain, fatigue and neurological and other functional impairments. Clinical manifestations can occur across the lifespan and vary substantially by disease onset and severity.

Efzimfotase alfa is an investigational enzyme replacement therapy (ERT) being developed as a potential next-generation option for a broader HPP population. The subcutaneous therapy is administered once every two weeks and replaces deficient ALP activity. Its less frequent dosing is intended to reduce injection burden compared with STRENSIQ (asfotase alfa), the currently approved ERT for certain patients with HPP.

Three-Trial Phase III Program Supports the BLA

The BLA is supported by the HICKORY, MULBERRY and CHESTNUT Phase III trials, which collectively enrolled 196 patients across 22 countries.

MULBERRY evaluated 29 treatment-naive children aged 2 to younger than 12 years. At week 25, efzimfotase alfa significantly improved the primary Radiographic Global Impression of Change (RGI-C) endpoint compared with placebo, with a median difference of 1.67 points (95% CI, 0.66–2.00; p=0.0003). The trial also met its key secondary endpoint for Rickets Severity Score, with a median difference of −1.00 (95% CI, −2.00 to −0.33; p=0.0008).

Several additional physical-function and quality-of-life measures showed nominal improvements. However, the Six-Minute Walk Test (6MWT) did not reach statistical significance, despite a median treatment difference of 34.5 meters (95% CI, −27.0 to 120.0; nominal p=0.4785). This distinction is important when interpreting the broader efficacy findings.

CHESTNUT enrolled 43 children aged 2 to younger than 12 years who had received STRENSIQ for at least six months. Patients switching to efzimfotase alfa had a similar incidence of treatment-emergent adverse events to those continuing STRENSIQ, at 90.5% and 86.4%, respectively. Bone-health measures indicated maintenance of therapeutic benefit after switching.

HICKORY evaluated 124 treatment-naive adolescents and adults aged 12 years and older. The trial showed a numerical improvement in its primary 6MWT endpoint but did not achieve statistical significance. Prespecified subgroups of patients with pediatric-onset HPP showed nominally significant and clinically meaningful improvements in mobility and other measures, while fatigue also improved in the overall study population.

Biweekly Dosing Could Reduce Injection Frequency

The dosing difference between efzimfotase alfa and STRENSIQ is a key development feature. STRENSIQ is administered subcutaneously at 2 mg/kg three times weekly or 1 mg/kg six times weekly under its US prescribing information.

By comparison, efzimfotase alfa is administered once every two weeks in the Phase III program. If approved, this would substantially reduce injection frequency while extending treatment to patients aged 2 years and older across different HPP disease-onset groups.

FDA Review Sets Up 2027 Regulatory Decision

FDA Priority Review carries a goal of action within six months of filing, compared with 10 months for standard review. AstraZeneca nevertheless identifies the anticipated PDUFA action date broadly as the first half of 2027, rather than providing a specific calendar date.

Full HICKORY results are scheduled for presentation at the 2026 American Society for Bone and Mineral Research (ASBMR) Annual Meeting. Regulatory submissions based on the three-trial program are also under review in Japan and other markets.

 Reference

Efzimfotase alfa granted Priority Review in the US as treatment for patients with hypophosphatasia aged 2 years and older, Astra Zeneca, 18 September 2026

Phase 3 Study of ALXN1850 in Treatment-Naïve Pediatric Participants With HPP (MULBERRY), ClinicalTrials.gov ID NCT06079359

Phase 3 Study of ALXN1850 in Pediatric Participants With HPP Previously Treated With Asfotase Alfa (CHESTNUT), ClinicalTrials.gov ID NCT06079372

Phase 3 Study of ALXN1850 Versus Placebo in Adolescent and Adult Participants With HPP Who Have Not Previously Been Treated With Asfotase Alfa (HICKORY), ClinicalTrials.gov ID NCT06079281