FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of July 2026
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Update on Ultomiris Phase III trial in
HSCT-TMA
27 July 2026
Update on Phase III trial
of Ultomiris in adults and adolescents with thrombotic
microangiopathy after haematopoietic stem cell
transplant
High-level results from the ALXN1210-TMA-313 Phase III clinical
trial showed that Ultomiris (ravulizumab) did not achieve statistical
significance for the primary endpoint of event-free survival
through 26 weeks compared to placebo in adults and adolescents
(aged 12 years or older) with thrombotic microangiopathy after
haematopoietic stem cell transplant (HSCT-TMA). The primary
endpoint was defined as the time from randomisation until
TMA-related clinical worsening or death, whichever occurred
first.
In paediatric patients with HSCT-TMA, the ALXN1210-TMA-314
open-label Phase III trial of Ultomiris demonstrated clinically meaningful overall
survival of 87.2% at 26 weeks and 73.4% at 52
weeks, as
previously disclosed.1,2 Alexion,
AstraZeneca Rare Disease is advancing regulatory filings
for Ultomiris in paediatric patients with HSCT-TMA, based
on these results and data from ALX-TMA-502, an external control
study, which further supports clinically meaningful benefit on
overall survival.1-3
Ultomiris showed
a trend
toward treatment benefit in adults and adolescents with
HSCT-TMA at 26 weeks compared to placebo. Discussions with
health authorities are ongoing regarding the interpretation of
these data, including in the context of real-world
evidence.3
Following HSCT, a procedure used with increasing frequency to treat
some types of cancers and other diseases, the devastating and
potentially life-threatening complication of TMA may
occur.4,5 TMA
can result in blood clots and damage to the walls of the smallest
blood vessels in the circulatory system, which may lead to organ
failure and death.6 HSCT-TMA
is estimated to affect fewer than 6,000 people in the
US.7
Christopher Dvorak, MD, Professor and Chief of the Division of
Pediatric Allergy, Immunology and Bone Marrow Transplantation at
UCSF Benioff Children's Hospitals, said: "Children who develop
HSCT-TMA have an extremely poor prognosis without targeted
treatment. While the scientific understanding of this condition
continues to evolve, survival remains a critical measure of
clinical benefit. The overall survival results observed in this
Phase III paediatric trial are clinically meaningful for this young
patient population with significant unmet need and may lead to a
targeted treatment option for children facing this serious,
post-transplant complication."
Vincent Ho, MD, Director
of Clinical Operations, Adult Hematopoietic Stem Cell
Transplantation and
Institute Physician at Dana-Farber Cancer Institute, Professor of
Medicine at Harvard Medical School, said:
"HSCT-TMA is a serious complication after stem cell transplant with
high rates of associated morbidity and mortality and for which
effective therapy remains an area of great unmet need. Conducting a
global, randomised trial in this complex, life-threatening,
post-transplant condition is exceedingly difficult. While the Phase
III trial in adults and adolescents did not meet the primary
endpoint, the results add new, important insights to advance the
field. Continued evaluation of these data together with results
collected from recent, real-world experience will further advance
clinical understanding and treatment of this complex transplant
complication."
Marc Dunoyer, Chief Executive Officer, Alexion, said: "As the
largest, global registrational programme conducted across a broad
population of patients with HSCT-TMA and the only
placebo-controlled trial in this adult
population, these
trials have demonstrated the potential of Ultomiris to
improve survival
in paediatric patients with this complex condition. We are moving
forward with regulatory filings, with the goal of bringing a
new treatment option to paediatric patients with HSCT-TMA and their
families as quickly as possible. At
the same time, we will continue engagement with global health
authorities on potential next steps for the adult indication, as we
advance additional analyses in the context of real-world
data."
The safety profile observed across the ALXN1210-TMA-313 and
ALXN1210-TMA-314 trials was consistent with the known safety
profile of Ultomiris and
with that seen in patients undergoing HSCT.
Alexion plans to present these data at a forthcoming medical
meeting.
Ultomiris has
been granted Orphan Drug Designation in the US and Japan for the
treatment of HSCT-TMA, as well as Breakthrough Therapy designation
by the US FDA for the treatment of paediatric patients
with HSCT-TMA.
Notes
HSCT-TMA
Haematopoietic stem cell transplant-associated thrombotic
microangiopathy (HSCT-TMA) is a rare, severe and potentially
life-threatening type of TMA that occurs following HSCT, a
procedure used with increasing frequency to treat some types of
cancers and other diseases.4,5 It
is thought that factors associated with HSCT (i.e., conditioning
regimens and other complications) induce overactivation and/or
dysregulation of the complement system, driving HSCT-TMA. Symptoms
of HSCT-TMA can overlap with those of other conditions, which can
lead to a misdiagnosis and/or a significant delay in receiving an
accurate diagnosis.4 HSCT-TMA
can be fatal, with one-year survival rates in paediatric patients
estimated between 17% and 44% and one-year overall survival rates
ranging from approximately 17% to 58% in adults, based upon
scientific literature.8-10
TMAs are a group of severe and potentially life-threatening rare
disorders that cause blood clots and damage to the walls of the
smallest blood vessels in the circulatory system. These blood clots
can cause injury to organs that may lead to organ failure and
death.6 Signs,
symptoms and complications of TMA include
organ damage (most commonly in the kidneys), low platelet count,
red blood cell abnormalities [i.e. anaemia, fragmented red cells
(schistocytes)], blood clots and high blood
pressure.11-14
ALXN1210-TMA-313
ALXN1210-TMA-313 is a global, Phase III, randomised, double-blind,
placebo-controlled, multicentre trial evaluating the safety and
efficacy of Ultomiris in
adult and adolescent (aged 12 years or older) participants who have
thrombotic microangiopathy (TMA) after haematopoietic stem cell
transplant (HSCT). Participants were required to have received HSCT
within the past 12 months at the time of screening, as well as a
diagnosis of TMA that persisted for at least 72 hours after the
initial management of any triggering condition or
agent.15
The dosing regimen was confirmed in an open-label, single-arm
period (Stage 1) based on data analysis after 14 participants had
completed 21 days of treatment. Patients enrolled thereafter in the
study were randomised 1:1 to receive either Ultomiris or
placebo administered intravenously for a total of 26 weeks, in
addition to best supportive care (Stage 2). Patients in the Stage 2
treatment arm received a loading dose of Ultomiris on
Days 1, 5 and 10, followed by regular weight-based maintenance
dosing of Ultomiris beginning
on Day 15, every eight weeks through the treatment period. Upon
completion of the treatment period, participants were followed for
an additional 26 weeks.15
The primary endpoint is event-free survival during the 26-week
treatment period, defined as the time from randomisation until
clinical worsening or death. Key secondary endpoints
include overall
survival, non-relapse mortality and TMA response criteria. The
trial enrolled 146 patients from 18 countries across North America,
South America, Europe, Asia and Australia.15
ALXN1210-TMA-314
ALXN1210-TMA-314 is a global, Phase III, open-label, single-arm,
multicentre study evaluating the safety and efficacy
of Ultomiris in
paediatric patients (aged 28 days to less than 18 years of age)
with thrombotic microangiopathy (TMA) after haematopoietic stem
cell transplantation (HSCT). Participants were required to have
received HSCT within the past 12 months at the time of screening,
as well as a diagnosis of TMA that persisted for at least 72 hours
after the initial management of any triggering condition or
agent.16
The dosing regimen was confirmed based on data analysis after at
least 10 participants had completed 21 days of treatment. All
patients received a loading dose of Ultomiris on
Days 1, 5 and 10, followed by regular weight-based maintenance
dosing of Ultomiris beginning
on Day 15 and administered every four weeks for patients weighing
less than 20 kg or every eight weeks for patients weighing at least
20 kg through the 26-week treatment period, in addition to best
supportive care. The administration of supplemental doses
of Ultomiris between
maintenance doses was guided by prespecified protocol
requirements.16
The primary endpoint is complete TMA response (defined as a
composite measure of haematologic and renal parameters) at 26
weeks. Secondary endpoints include overall survival, non-relapse
mortality and TMA response criteria. Upon completion of the
treatment period, patients were followed for an additional 26
weeks. The trial enrolled 41 patients from seven countries across
North America, Europe and Asia.16
ALX-TMA-502
ALX-TMA-502 is a global, observational, secondary real-world,
retrospective study to assess overall survival in adult and
paediatric participants (≥ 28 days of age at the time of
diagnosis) diagnosed with HSCT-TMA within 52 weeks after stem cell
transplantation. The study included two cohorts (complement
inhibitor treatment-naïve participants and participants
treated with eculizumab) for adult and paediatric participants,
respectively. The HSCT-TMA diagnosis was required to have occurred
at least 52 weeks before the eligibility assessment
date.3
The study was conducted to provide historical control data and
real-world contextualisation in the treatment of HSCT-TMA. The
primary endpoint is overall survival through 52 weeks after
diagnosis, defined as the number of days from the date of TMA
diagnosis to the date of death. Secondary endpoints include overall
survival at 100 days and 26 weeks after diagnosis; and non-relapse
mortality through 100 days, 26 weeks, and 52 weeks after diagnosis.
In this study, data were collected from 307 patients in 10
countries across North America, South America, Europe, and
Asia.3
Ultomiris
Ultomiris (ravulizumab),
the longest-acting C5 complement inhibitor, provides immediate,
complete and sustained complement inhibition. The medication works
by inhibiting the C5 protein in the terminal complement cascade, a
part of the body's immune system. When activated in an uncontrolled
manner, the complement cascade over-responds, leading the body to
attack its own healthy cells. Following a loading
dose, Ultomiris is
administered intravenously every eight weeks in adults, or every
four or eight weeks in paediatric patients (based on body
weight).
Ultomiris is
approved in the US, EU, Japan and other countries for the treatment
of certain adults with paroxysmal nocturnal haemoglobinuria (PNH)
and is also approved for certain children with PNH in the US, EU
and other countries.
Ultomiris is
also approved in the US, EU, Japan and other countries for the
treatment of certain adults and children with atypical haemolytic
uraemic syndrome (aHUS).
Additionally, Ultomiris is approved in the US, EU, Japan, China and
other countries for the treatment of certain adults with
generalised myasthenia gravis (gMG).
Further, Ultomiris is
approved in the US, EU, Japan, China and other countries for the
treatment of certain adults with neuromyelitis
optica spectrum disorder (NMOSD).
Ultomiris is
being assessed as a treatment for additional indications as part of
a broad development programme.
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.
Schoettler M, et al. Ravulizumab plus best supportive care to treat
pediatric patients with hematopeietic stem cell
transplantation-associated thrombotic microangiopathy: first
results from a Phase 3 trial. Presented at European Hematology
Association 2025 Congress; 12-15 June 2025; Milan, Italy. Abstract
S269.
2. Schoettler M, et al. Ravulizumab
plus best supportive care in pediatric patients with hematopoietic
stem cell transplantation-associated thrombotic microangiopathy:
52-week results from a Phase 3 trial. Presented
at Transplantation & Cellular Therapy Meetings of ASTCT and
CIBMTR Congress; 4-7 February 2026; Salt Lake City, Utah.
Presentation 80.
3. ALX-TMA-502 Study.
AlexionClinicalTrialTransparency.com. Available here.
Accessed July 2026.
4. Meri S, et al. The role of
complement in HSCT-TMA: basic science to clinical
practice. Adv Ther. 2022;39(9):3896-3915.
5. Atsuta Y, et al. Continuous and
differential improvement in worldwide access to hematopoietic cell
transplantation: activity has doubled in a decade with a notable
increase in unrelated and non-identical related
donors. Haematologica.
2024;109(10):3282-3294.
6. Brocklebank V, et al. Thrombotic
microangiopathy and the kidney. Clin J Am Soc
Nephrol.
2018;13:300-317.
7. 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 July 2026.
8. Jodele S, et al. Diagnostic and
risk criteria for HSCT-associated thrombotic microangiopathy: a
study in children and young adults. Blood. 2014;124(4):645-653.
9. Matsui H, et al. Risk factors and
appropriate therapeutic strategies for thrombotic microangiopathy
after allogeneic HSCT. Blood Adv. 2020;4(13):3169-3179.
10. Vasu S, et al. High incidence of severe
TA-TMA increases mortality in adult allogeneic transplant
recipients: a prospective MIDAS Consortium
study. Blood. 2025;146(5):638-646.
11. Raina R, et al. Atypical
hemolytic-uremic syndrome: an update on pathophysiology, diagnosis,
and treatment. Ther Apher
Dial.
2019;23(1):4-21.
12. Sallée M, et al. Myocardial
infarction is a complication of factor H-associated atypical
HUS. Nephrol Dial
Transplant.
2010;25(6):2028-2032.
13. Laurence J, et al. Atypical hemolytic
uremic syndrome (aHUS): essential aspects of an accurate
diagnosis. Clin Adv Hematol
Oncol.
2016;11(11):2-15.
14. Vorobev A, et al. The phenomenon of
thrombotic microangiopathy in cancer
patients. Int. J. Mol. Sci. 2024;25(16):9055.
15. ClinicalTrials.gov. Ravulizumab in
Thrombotic Microangiopathy After Hematopoietic Stem Cell
Transplant. NCT Identifier: NCT04543591.
Available here.
Accessed July 2026.
16. ClinicalTrials.gov. Study of Ravulizumab
in Pediatric Participants With HSCT-TMA. NCT Identifier:
NCT04557735. Available here.
Accessed July 2026.
Matthew Bowden
Company Secretary
AstraZeneca PLC
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.
Date:
27 July 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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