FORM 6-K
SECURITIES
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AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Efzimfotase alfa Ph3 program show positive results
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 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.
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.
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.
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.
Accessed March 2026.
Matthew Bowden
Company Secretary
AstraZeneca PLC
This announcement contains information that AstraZeneca PLC is
obliged to make public pursuant to the EU Market Abuse Regulation
(596/2014) and the assimilated EU Market Abuse Regulation
(596/2014) as it forms part of the law of the United Kingdom by
operation of the European Union (Withdrawal) Act 2018. This
announcement was submitted for publication, through the
agency of the contact person(s) set out above, at 7:00 BST on 31
March 2026.
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
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AstraZeneca
PLC
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Date:
31 March 2026
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By: /s/
Matthew Bowden
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Name:
Matthew Bowden
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Title:
Company Secretary
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