REG - AstraZeneca PLC - Gefurulimab nanobody met Phase III endpoints

AstraZenecaAnnouncement

24/07/2025 07:00

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RNS Number : 3265S  AstraZeneca PLC  24 July 2025

24 July 2025

 

Gefurulimab dual-binding nanobody demonstrated statistically significant and
clinically meaningful improvement in functional activities of daily living in
adults with generalised myasthenia gravis in PREVAIL Phase III trial

 

Once-weekly self-administered subcutaneous C5 inhibitor showed statistically
significant and clinically meaningful reduction in disease severity at week 26
 

 

Positive high-level results from a global, randomised, double-blind,
placebo-controlled Phase III trial in adults with anti-acetylcholine receptor
(AChR) antibody-positive (Ab+) generalised myasthenia gravis (gMG) showed that
gefurulimab met its primary and all secondary endpoints. Data demonstrated a
statistically significant and clinically meaningful improvement from baseline
in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score at week
26 compared to placebo.

 

gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that
leads to a loss of muscle function and severe weakness.(1) Those living with
gMG may initially experience slurred speech, double vision, droopy eyelids and
weakness, with symptoms becoming more severe as the disease progresses,
including extreme fatigue, difficulty swallowing, choking and respiratory
failure.(2,3)

 

Kelly Gwathmey, MD, Associate Professor of Neurology, Chief of Neuromuscular
Division, Virginia Commonwealth University, Richmond, VA, Vice Chair of the
MGFA Medical & Scientific Advisory Council and principal investigator in
the trial, said: "Rapidly fluctuating symptoms and the unpredictable
disability associated with gMG can affect nearly every aspect of a patient's
life, making early intervention and sustained disease control a critical
treatment goal. A once-weekly, self-administered C5 treatment option would
offer patients greater convenience and independence in managing their
condition, empowering them to have more control over their therapy."

 

Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease,
said: "Building on Alexion's pioneering leadership in gMG, these positive
results from the PREVAIL Phase III trial demonstrate the potential for
gefurulimab to offer rapid and sustained disease control for this patient
community. These data, reflecting patient participation across 20 countries,
reinforce the established safety profile and efficacy of C5 inhibition and
show the potential for gefurulimab as a first line biologic, with the
convenience of a self-administered option."

 

Gefurulimab was well-tolerated, and the safety profile was consistent with
previous trials of C5 inhibitors in gMG with no new safety signals observed.
These data will be presented at a forthcoming medical meeting and shared with
global regulatory authorities.

 

Notes

 

gMG

gMG is a rare autoimmune disorder characterised by loss of muscle function and
severe muscle weakness.(1)

 

Eighty-five percent of people with gMG are AChR antibody-positive meaning they
produce specific antibodies (anti-AChR) that bind to signal receptors at the
neuromuscular junction (NMJ), the connection point between nerve cells and the
muscles they control.(4) This binding activates the complement system, causing
the immune system to attack the NMJ, leading to inflammation and a breakdown
in communication between the brain and the muscles.(5)

 

gMG can occur at any age, but it most commonly begins for women before the age
of 40 and for men after the age of 60.(6) Initial symptoms may include slurred
speech, double vision, droopy eyelids and lack of balance; these can often
lead to more severe symptoms as the disease progresses such as, impaired
swallowing, choking, extreme fatigue and respiratory failure.(2,3)

 

Gefurulimab

Gefurulimab, an investigational complement C5 inhibitor, is a novel
dual-binding nanobody optimised for subcutaneous self-administration in
development as a treatment for AChR-Ab+ gMG. The investigational medication
works by binding to 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. Gefurulimab's concurrent binding to serum albumin provides an extended
half-life, enabling once-weekly dosing. Gefurulimab has been granted Orphan
Drug Designation in the US for the treatment of myasthenia gravis.

 

PREVAIL (ALXN1720-MG-301)

PREVAIL (ALXN1720-MG-301) is a global, Phase III, randomised, double-blind,
placebo-controlled, parallel, multicentre study evaluating the safety and
efficacy of gefurulimab in adults with generalised myasthenia gravis (gMG).
The trial enrolled 260 patients from 20 countries across North America,
Europe, Asia and the Pacific region. Participants were required to have a
confirmed myasthenia gravis diagnosis at least three months prior to the
screening visit with a positive serological test for autoantibodies against
AChR and Myasthenia Gravis Foundation of America Clinical Classification Class
II to IV at screening.(7)

 

Patients were randomised 1:1 to receive gefurulimab or placebo for a total of
26 weeks in the randomised controlled treatment period. Patients received a
single weight-based loading dose on Day 1, followed by regular weight-based
maintenance dosing beginning on Day 8 and once every week thereafter. The
primary endpoint of the change from baseline in the Myasthenia Gravis
Activities of Daily Living (MG-ADL) total score, a patient-reported scale that
assesses patients' abilities to perform daily activities, was assessed at week
26 along with multiple secondary endpoints evaluating improvement in
disease-related measures.(7)

 

Patients who completed the randomised controlled treatment period were
eligible to continue into an open-label extension period evaluating the safety
and efficacy of gefurulimab, which is ongoing.(7)

 

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/Nasdaq: 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, AstraZeneca's 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.   Jung-Plath W, et al. Assessment of myasthenia gravis patients' quality
of life. The Journal of Neurological and Neurosurgical Nursing.
2023;12(2):74-83.

2.   Catalin J, et al. Clinical presentation of myasthenia gravis. Thymus.
2019.

3.   Farid ZR, et al. Factors affecting generalization of ocular myasthenia
gravis. Sriwijaya Journal of Ophthalmology. 2020;3(2):48-54.

4.   Lazaridis K, et al. Myasthenia gravis: autoantibody specificities and
their role in MG management. Front Neurol. 2020;11:596981.

5.   Huang YF, et al. Visualization and characterization of complement
activation in acetylcholine receptor antibody seropositive myasthenia gravis.
Muscle Nerve. 2024.

6.   Cavanagh N, et al. Exploring the impairments and allied health
professional utilization in people with myasthenia gravis: a cross-sectional
study. J Clin Neurosci. 2023;114:9-16.

7.   ClinicalTrials.gov. Safety and efficacy of ALXN1720 in adults with
generalized myasthenia gravis. NCT Identifier: NCT05556096. Available here
(https://clinicaltrials.gov/study/NCT05556096?cond=Generalized%20Myasthenia%20Gravis&aggFilters=status:act&rank=1)
. Accessed July 2025.

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

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