AstraZeneca: Efzimfotase alfa granted Priority Review in the US as treatment for patients with hypophosphatasia aged 2 years and older

Alexion, AstraZeneca's Rare Disease's Biologics License Application (BLA) for efzimfotase alfa has been accepted and granted Priority Review by the US Food and Drug Administration (FDA) for the treatment of patients with hypophosphatasia (HPP) aged ≥2 years.

The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available treatment options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for its regulatory decision, is anticipated during the first half of 2027.

HPP is a rare, chronic, inherited metabolic disease caused by deficient activity of the enzyme alkaline phosphatase (ALP), characterised by defective bone mineralisation, impaired calcium and phosphate regulation and functional impairments, such as muscle weakness, neurologic symptoms, generalised fatigue and pain.1.2

Marc Dunoyer, Chief Executive Officer, Alexion, said: "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."

The BLA is based on results from the efzimfotase alfa Phase III clinical programme, which is comprised of three trials, HICKORY in adolescents and adults (12 years of age and older) who have not been previously treated with Strensiq (asfotase alfa), MULBERRY in children (2 to <12 years of age) who have not been previously treated with Strensiq and CHESTNUT in children previously treated with Strensiq. 

Results from the MULBERRY and CHESTNUT trials were recently presented at the 12th International Conference on Children's Bone Health (ICCBH). Results from the HICKORY trial will be presented at the upcoming 2026 American Society for Bone and Mineral Research (ASBMR) Annual Meeting.4

Efzimfotase alfa demonstrated a favourable safety profile and was generally well-tolerated across all three Phase III clinical trials.4

Regulatory submissions for efzimfotase alfa based on MULBERRY, CHESTNUT and HICKORY are also under review in Japan and other markets.

Notes

Hypophosphatasia

Hypophosphatasia (HPP) is a rare, chronic, inherited metabolic disease caused by deficient activity of the enzyme alkaline phosphatase (ALP), which is important for building healthy bones and supporting proper muscle function.1 HPP is characterised by defective mineralisation (the process that hardens and strengthens bones and teeth), impaired calcium and phosphate regulation and functional impairments, such as muscle weakness, neurologic symptoms, generalised fatigue and pain that can be debilitating.1,2 HPP can be progressive, and clinical manifestations may occur at any age and evolve over time.1 The addressable HPP patient population is estimated at 13,800 across the US, Germany, France, UK, Italy, Spain, Japan and China.3 HPP affects people of all ages, with approximately 80% of people living with HPP being adults.1,2,5

MULBERRY

MULBERRY is a global Phase III randomised, double-blind, placebo-controlled, multicentre trial evaluating the efficacy and safety of efzimfotase alfa (ALXN1850) in paediatric patients (2 to <12 years of age) with hypophosphatasia (HPP) who have not been previously treated with Strensiq (asfotase alfa). The trial enrolled 29 patients from 14 countries across North America, South America, Europe and Asia.6

Patients were required to have an HPP diagnosis and the presence of HPP-related rickets on skeletal X-rays and low serum alkaline phosphatase (ALP) activity. Eligible patients also needed to demonstrate either a variant in ALPL, the gene encoding ALP, or elevated levels of plasma pyridoxal 5'-phosphate (PLP), a biomarker of HPP.6

Patients were randomised 2:1 to receive efzimfotase alfa at one of three doses based on predefined weight ranges or placebo, once every two weeks via subcutaneous injection for 24 weeks. The primary endpoint Radiographic Global Impression of Change (RGI-C) Score was assessed at the end of the randomised evaluation period (Day 169), along with multiple secondary endpoints measuring skeletal health and physical function, including change from baseline in the Rickets Severity Score (RSS), Six-Minute Walk Test (6MWT), Bruininks-Oseretsky Test of Motor Proficiency Score (BOT-2) and Peabody Developmental Motor Scales Score (PDMS-3).6

Patients who completed the randomised evaluation period were eligible to continue into an open-label extension period evaluating the safety and efficacy of efzimfotase alfa, which is ongoing.6

CHESTNUT

CHESTNUT is a global Phase III randomised, open-label, active-controlled, multicentre trial evaluating the safety and tolerability of efzimfotase alfa in paediatric patients (2 to <12 years of age) with hypophosphatasia (HPP) who have been treated with 6 mg/kg per week of Strensiq (asfotase alfa) for at least 6 months prior to study initiation. The trial enrolled 43 patients from seven countries globally.7

Patients were required to have an HPP diagnosis and have been treated with Strensiq for at least 6 months before the start of the trial with open growth plates confirmed by X-ray.7

Patients were randomised 1:1 to receive efzimfotase alfa at one of three doses based on predefined weight ranges once every two weeks or 6 mg/kg/week of Strensiq via 3x or 6x subcutaneous injections per week for 24 weeks. The primary endpoint is the incidence of treatment-emergent adverse events (TEAEs) at the end of the randomised evaluation period. Key secondary endpoints include change from baseline in the Rickets Severity Score (RSS) and Radiographic Global Impression of Change (RGI-C).7

Patients who completed the randomised evaluation period were eligible to continue into an open-label extension period evaluating the safety and efficacy of efzimfotase alfa, which is ongoing.7

HICKORY
HICKORY is a global Phase III randomised, double-blind, placebo-controlled, multicentre trial evaluating the efficacy and safety of efzimfotase alfa (ALXN1850) in adolescents (12 to <18 years of age) and adults with hypophosphatasia (HPP) who have not been previously treated with Strensiq (asfotase alfa). The trial enrolled 124 patients from 17 countries across North America, South America, Europe, Asia and Australia.8

Patients were required to have an HPP diagnosis and either a variant in ALPL, the gene encoding alkaline phosphatase (ALP), or elevated levels of plasma pyridoxal 5'-phosphate (PLP), a biomarker of HPP. Eligible patients needed to demonstrate low ALP levels and two separate Six-Minute Walk Tests (6MWTs) below 85% of the predicted distance adjusted for age, sex, weight and height, without a probable cause other than HPP.8

Patients were randomised 2:1 to receive efzimfotase alfa at one of three doses based on predefined weight ranges or placebo, once every two weeks via subcutaneous injection for 24 weeks. The primary endpoint of change from baseline in 6MWT was assessed at the end of the randomised evaluation period (Day 169), along with multiple key secondary endpoints measuring physical function, pain, fatigue, quality of life and safety, including change from baseline in 30-second Sit to Stand (STS) Test Score, Lower Extremity Functional Scale (LEFS) Score, Brief Pain Inventory Short Form (BPI-SF) Score and Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score.8

Patients who completed the randomised evaluation period were eligible to continue into an open-label extension period evaluating the safety and efficacy of efzimfotase alfa, which is ongoing.8

Efzimfotase Alfa (ALXN1850)

Efzimfotase alfa (ALXN1850) is an investigational enzyme replacement therapy (ERT) designed to demonstrate efficacy and safety in a broad range of patients with hypophosphatasia (HPP) aged ≥ 2 years, including patients without overt bone manifestations. Efzimfotase alfa is being developed as a subcutaneous treatment administered every two weeks to replace the deficient alkaline phosphatase (ALP) enzyme activity that is the underlying cause of HPP. Efzimfotase alfa has been granted Priority Review by the US FDA for the treatment of patients with HPP aged 2 years and older.

Strensiq (asfotase alfa)

Strensiq is a bone-targeted enzyme replacement therapy designed to address the underlying cause of hypophosphatasia (HPP) - deficient alkaline phosphatase (ALP). By replacing deficient ALP, treatment with Strensiq aims to improve the elevated enzyme substrate levels and improve the body's ability to mineralise bone, thereby preventing serious skeletal and systemic patient morbidity and premature death.

Strensiq is approved in the US, EU, Japan and other countries for the treatment of certain patients with HPP. Strensiq has been granted orphan drug designation by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japanese Ministry of Health, Labour and Welfare (MHLW).

Alexion

Alexion, AstraZeneca Rare Disease, is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US.

AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

Contacts
For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.

References

1. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013;10(2):380-388.
2. Dahir KM, et al. Clinical profiles of treated and untreated adults with hypophosphatasia in the Global HPP Registry. Orphanet J Rare Dis. 2022;17(1):277.
3. AstraZeneca Data on File - Epidemiology estimates are composed of a triangulation of different data sources including Data Monitor, Decision Resources Group, Kantar Health, and internal input. Available here. Accessed September 2026.
4. Efficacy and Safety of Alkaline Phosphatase (ALP) Enzyme Replacement Therapy (ERT) Efzimfotase Alfa in Children with Hypophosphatasia (HPP): Results of MULBERRY and CHESTNUT as Part of a Three-trial Phase 3 Clinical Program. Presented at the International Conference on Children's Bone Health; 2026 June 28; Montreal, Canada.
5. Fang S, et al. Diagnosed prevalence of hypophosphatasia: a retrospective analysis of electronic health records in the United States. Poster presented at ASBMR 2025 Annual Meeting; September 5-8, 2025; Seattle, WA.
6. ClinicalTrials.gov. Phase 3 study of ALXN1850 in treatment-naïve pediatric participants with HPP (MULBERRY). NCT Identifier: NCT06079359. Available here. Accessed September2026.
7. ClinicalTrials.gov. Phase 3 study of ALXN1850 in pediatric participants with HPP previously treated with asfotase alfa (CHESTNUT). NCT Identifier: NCT06079372. Available here. Accessed September 2026.
8. ClinicalTrials.gov. Phase 3 study of ALXN1850 versus placebo in adolescent and adult participants with HPP who have not previously been treated with asfotase alfa (HICKORY). NCT Identifier: NCT06079281. Available here. Accessed September 2026.