REG - AstraZeneca PLC - Efzimfotase alfa Ph3 program show positive results

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RNS Number : 7141Y  AstraZeneca PLC  31 March 2026

This announcement contains inside information

 

31 March 2026

 

Efzimfotase alfa demonstrated positive results from global Phase III
clinical programme in hypophosphatasia

 

MULBERRY randomised, placebo-controlled trial showed efzimfotase alfa
demonstrated statistically significant and clinically meaningful improvement
in bone health in treatment-na•ve paediatric patients

 

CHESTNUT randomised, open-label, active-controlled trial demonstrated safety
and tolerability of efzimfotase alfa in paediatric patients previously treated
with Strensiq with maintenance of therapeutic benefit

 

HICKORY randomised, placebo-controlled trial showed numerical improvement but
did not achieve statistical significance in the primary endpoint in
treatment-na•ve adolescents and adults; results indicate clinically
meaningful benefit in a combination of prespecified subgroups of adolescents
and adults with paediatric-onset HPP

 

The efzimfotase alfa (ALXN1850) Phase III clinical programme, designed to
study a broad hypophosphatasia (HPP) patient population, demonstrated positive
results.  The global clinical programme, which included two randomised,
placebo-controlled trials and one randomised, open-label, active-controlled
paediatric switch trial, enrolled 196 patients spanning children, adolescents
and adults with either paediatric-onset or adult-onset HPP across 22
countries.

 

Addressing unmet needs for people living with HPP

Efzimfotase alfa is an investigational enzyme replacement therapy designed to
offer lower injection volume, less frequent dosing over Strensiq (asfotase
alfa) and close critical gaps in care within the broader HPP patient
population.

 

Paediatric clinical trials

The MULBERRY Phase III trial in children (2 to <12 years of age) with HPP
who have not been previously treated with Strensiq, showed that efzimfotase
alfa met its primary endpoint. Results demonstrated a statistically
significant and clinically meaningful improvement in bone health from baseline
compared to placebo, as measured by Radiographic Global Impression of Change
(RGI-C) Score at week 25. In addition, statistically significant improvement
was observed in the key secondary endpoint of change from baseline in Rickets
Severity Score (RSS) at week 25. Additional secondary endpoints measuring
physical function (Six-Minute Walk Test) and motor proficiency (Paediatric
Outcomes Data Collection Instrument or PODCI) further supported the overall
clinical benefit of efzimfotase alfa in the paediatric population.

 

Positive high-level results from the CHESTNUT Phase III trial showed that
efzimfotase alfa was well-tolerated and demonstrated a favourable safety
profile in paediatric patients (2 to <12 years of age) switching from
Strensiq and maintained the treatment benefit of Strensiq on bone health at
week 25, as measured by secondary endpoints RGI-C and RSS.

 

Adolescent and adult clinical trial

In the HICKORY Phase III trial, efzimfotase alfa showed numerical improvement
but did not achieve statistical significance in the primary endpoint of
Six-Minute Walk Test (6MWT) in adolescents and adults (12 years of age and
older) with HPP who have not been previously treated with Strensiq, compared
to placebo at week 25. This was largely due to better-than-expected results
observed in the adult-onset HPP placebo group. However, treatment with
efzimfotase alfa demonstrated nominally significant improvements in Functional
Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in the overall
study population.

 

In a combination of prespecified subgroups of adolescents and adults with
paediatric-onset HPP, efzimfotase alfa showed nominally statistically
significant and clinically meaningful benefits in mobility, as measured by
6MWT, as well as key secondary endpoints measuring physical function and pain
reduction, compared to placebo.

 

Initial findings from the ongoing, long-term, open-label extension of the
HICKORY trial show continued improvement in the primary and key secondary
endpoints at week 48. Participants who switched from placebo to efzimfotase
alfa after the randomised period also showed clinically meaningful
improvements across multiple efficacy outcomes after 24 weeks of treatment.

 

Efzimfotase alfa was well-tolerated and had an acceptable safety profile
across the MULBERRY, CHESTNUT and HICKORY clinical trials.

 

Eric Rush, MD, Clinical Geneticist, ChildrenÕs Mercy Hospital Kansas,
Professor of Paediatrics, University of Missouri-Kansas City School of
Medicine and lead principal investigator in the MULBERRY trial, said: ÒThe
results from the global MULBERRY clinical trial demonstrate efzimfotase
alfaÕs potential to address the underlying pathophysiology of HPP and to
prevent and reverse the substantial skeletal and functional impacts of this
lifelong rare disease. I am encouraged by these results and the potential for
this innovative, investigational therapy to redefine care in HPP with a
convenient self-administered option taken every two weeks.Ó

 

Kathryn Dahir, MD, Director of the Programme for Metabolic Bone Disorders at
Vanderbilt Health and Associate Director for Clinical Research Translation,
Professor in the Department of Internal Medicine, Division of Endocrinology,
Diabetes and Metabolism and lead investigator in the HICKORY trial, said:
ÒFindings from the broad HICKORY registrational trial, the first to include
patients with adult-onset disease, highlight the heterogeneity of the disease
and the value of assessing a range of clinically meaningful endpoints across
diverse patient populations. The results indicate a clinically relevant impact
on mobility, physical function, pain and fatigue, demonstrating the potential
for efzimfotase alfa to improve outcomes for patients living with this
disease.Ó

 

Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease,
said: ÒThe efzimfotase alfa clinical programme, comprised of three global
Phase III trials, was the first to include patients with both paediatric- and
adult-onset HPP with heterogeneous manifestations beyond bone. We are
encouraged by the improvements observed across this patient population who
exhibit a wide range of severity and clinical characteristics. Collectively,
these results support the potential for efzimfotase alfa to transform the
treatment paradigm for people living with this rare disease.Ó

 

These data will be presented at a forthcoming medical meeting and shared with
global regulatory authorities.

 

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 evolve over time. While diagnosis
rates vary by geography, there are an estimated 11,500 people diagnosed
with HPP across the US, Germany, France, UK, Italy, Spain, Japan and
China.(3-6) A recent study from the US estimated diagnosed prevalence at 2.8
per 100,000 people.(7) HPP affects people of all ages, with approximately 80%
of people living with HPP being adults.(1,2,7)

 

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.(8)

 

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.(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 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).(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)

 

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.(9)

 

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.(9)

 

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).(9)

 

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.(9)

 

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.(10)

 

Patients were required to have a 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) at
or below 85% of the predicted distance adjusted for age, sex, weight and
height, without a probable cause other than HPP.(10)

 

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 Ð Fatigue
(FACIT-Fatigue) Score.(10)

 

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.(10)

 

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 ³2 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.

 

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 Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZenecaÕs innovative medicines are
sold in more than 125 countries and used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com/)  and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca) .

 

Contacts
For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

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.   Tornero C, et al. Can we identify individuals with an ALPL variant in
adults with persistent hypophosphatasaemia? Orphanet J Rare Dis. 2020;15(51).

4.   Held CM, et al. Screening for hypophosphatasia: does biochemistry lead
the way? J Pediatr Endocrinol Metab. 2021 Sep 22;35(2):169-178.

5.   Gonz‡lez-Cejudo T, et al. Mild hypophosphatasia may be twice as
prevalent as previously estimated: an effective clinical algorithm to detect
undiagnosed cases. Clinical Chemistry and Laboratory Medicine (CCLM).
2024;62(1):128-137.

6.   Dahir KM, et al. Hypophosphatasia: low penetrance of pathogenic and
likely-pathogenic ALPL variants identified through an unselected
biorepository. Journal of Bone and Mineral Research. 2026; 41(3):270Ð281.

7.   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.

8.   ClinicalTrials.gov. Phase 3 study of ALXN1850 in treatment-na•ve
pediatric participants with HPP (MULBERRY). NCT Identifier: NCT06079359.
Available here (https://clinicaltrials.gov/study/NCT06079359) . Accessed March
2026.

9.   ClinicalTrials.gov. Phase 3 study of ALXN1850 in pediatric participants
with HPP previously treated with asfotase alfa (CHESTNUT). NCT Identifier:
NCT06079372. Available here (https://clinicaltrials.gov/study/NCT06079372) .
Accessed March 2026.

10.  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 (https://clinicaltrials.gov/study/NCT06079281) . Accessed March 2026.

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

 

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of the United Kingdom by operation of the European Union (Withdrawal) Act
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the contact person(s) set out above, at 7:00 BST on 31 March 2026.

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