a6051p
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 June 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Eplontersen Ph III trial met co-primary endpoints
21 June 2022 07:00 BST
Eplontersen met co-primary and secondary endpoints in interim
analysis of the NEURO-TTRansform Phase III trial for
hereditary transthyretin-mediated amyloid
polyneuropathy
(ATTRv-PN)
New Drug Application filing anticipated based on positive data from
interim analysis
Positive high-level results from the NEURO-TTRansform Phase III
trial in patients with hereditary transthyretin-mediated amyloid
polyneuropathy (ATTRv-PN) showed AstraZeneca and Ionis'
eplontersen met its co-primary endpoints in a planned interim
analysis at 35 weeks. In the trial, eplontersen reached a
statistically significant and clinically meaningful change from
baseline for its co-primary endpoint of percent change in serum
transthyretin (TTR) concentration, reducing TTR protein production.
Eplontersen also reached its co-primary endpoint of change from
baseline in the modified Neuropathy Impairment Score +7 (mNIS+7), a
measure of neuropathic disease progression1,
versus external placebo group.
High-level results showed the trial also met its secondary endpoint
of change from baseline in the Norfolk Quality of Life
Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) showing
treatment with eplontersen significantly improved patient-reported
quality of life versus external
placebo group. In
the trial, eplontersen demonstrated a favourable safety and
tolerability profile with no specific concerns.
ATTRv-PN is a debilitating disease that leads to
peripheral nerve damage with motor disability within five years of
diagnosis and, without treatment, is generally fatal within a
decade3. Eplontersen, formerly
known as IONIS-TTR-LRx,
is a ligand-conjugated antisense (LICA) investigational medicine
designed to reduce the production of TTR protein at its source to
treat both hereditary and non-hereditary forms of
ATTR2,4-6.
Teresa
Coelho, M.D., a neurologist and neurophysiologist at Hospital Santo
António, Centro Hospitalar Universitário do Porto,
Portugal and an investigator for the NEURO-TTRansform trial, said:
"These encouraging data reinforce the safety profile of eplontersen
and demonstrate clear evidence of its potential to provide much
needed therapeutic benefit to patients living with hereditary
transthyretin-mediated amyloid polyneuropathy."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "Amyloid transthyretin polyneuropathy
is a rare and fatal disease that can affect up to 40,000 people
worldwide. These promising results show eplontersen has the
potential to be a new and much needed treatment where limited
options exist and significant unmet medical need
remains."
Based on the 35-week interim trial results, the companies will seek
regulatory approval for eplontersen and plan to file a new drug
application with the US Food and Drug Administration in
2022. ATTRv-PN
is expected to be the first indication for which AstraZeneca and
Ionis will seek regulatory approval for eplontersen.
The results
from the 35-week interim analysis of the trial will
be submitted for presentation at
a forthcoming medical meeting.
As part of a global
development and commercialisation agreement with
Ionis, eplontersen will be jointly developed and commercialised by
both companies in the US and will be developed and commercialised
in the rest of the world by AstraZeneca (with the exception of
Latin America).
Eplontersen was granted Orphan
Drug Designation in the US and
is also currently being evaluated in the CARDIO-TTRansform Phase
III trial for amyloid transthyretin
cardiomyopathy (ATTR-CM)4,6,
a systemic, progressive and fatal condition that leads to
progressive heart failure and death within four years from
diagnosis7-9.
Notes
TTR Amyloidosis
ATTR cardiomyopathy and polyneuropathy are progressive systemic
diseases caused by aging or genetic mutations, resulting in
misfolded TTR protein and accumulation as amyloid fibrils in the
cardiac myocardium and peripheral nerves,
respectively2,6-8.
In patients with ATTR, both hereditary and wild type
(non-hereditary), TTR protein builds up as fibrils in tissues, such
as the peripheral nerves and heart, gastrointestinal system, eyes,
kidneys, central nervous system, thyroid and bone
marrow7,8,10.
The presence of TTR fibrils interferes with the normal functions of
these tissues8.
As the TTR protein fibrils accumulate, more tissue damage occurs
and the disease worsens, resulting in poor quality of life (QoL)
and eventually death8.
Worldwide, there are an estimated 300,000 - 500,000 patients with
ATTR-CM10 and
about 40,000 patients with ATTRv-PN8.
NEURO-TTRansform
NEURO-TTRansform is a global, open-label, randomised trial
evaluating the efficacy and safety of eplontersen in patients with
ATTRv-PN2,5.
The trial has enrolled adult patients with ATTRv-PN Stage 1 or
Stage 2 and will be compared to the external placebo
group from the TEGSEDI® (inotersen)
NEURO-TTR registrational trial that Ionis completed in
20172,5.
The final primary endpoint analysis will be completed at week 66
and all patients will be followed until week 85, when they will
have the option to transition into the open-label extension
trial2.
The co-primary endpoints in the interim analysis were percent
change from baseline in serum TTR concentration and change in the
mNIS+7 versus external placebo group at week
352,5.
The mNIS+7 uses highly standardised, quantitative, and referenced
assessments to quantify muscle weakness, muscle stretch reflexes,
sensory loss, and autonomic impairment1.
The secondary endpoint was change from baseline in the Norfolk
QoL-DN score versus external
placebo group at
week 352,5.
The Norfolk QoL-DN is a patient-reported questionnaire capturing
neuropathy-related QoL11.
Eplontersen
Eplontersen is
a LICA investigational medicine designed to reduce the production
of transthyretin, or TTR protein, to treat all types of ATTR, a
systemic, progressive and fatal disease2,4-6.
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of
BioPharmaceuticals, forms one of AstraZeneca's three disease areas
and is a key growth driver for the Company. By following the
science to understand more clearly the underlying links between the
heart, kidneys and pancreas, AstraZeneca is investing in a
portfolio of medicines for organ protection and improving outcomes
by slowing disease progression, reducing risks and tackling
co-morbidities. The Company's ambition is to modify or halt the
natural course of CVRM diseases, and potentially regenerate organs
and restore function, by continuing to deliver transformative
science that improves treatment practices and CV health for
millions of patients worldwide.
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 operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Dyck
PJB, et al. Development
of measures of polyneuropathy impairment in hATTR amyloidosis: from
NIS to mNIS +7. J Neurol
Sci. 2019;405:116424.
2. Coelho T, et al. Design and
Rationale of the Global Phase 3 NEURO-TTRansform Study of Antisense
Oligonucleotide AKCEA-TTR-LRx(ION-682884-CS3) in Hereditary
Transthyretin-Mediated Amyloid
Polyneuropathy. Neurol Ther. 2021 Jun;10(1):375-389.
3. Cortese A, et al. Diagnostic
challenges in hereditary transthyretin amyloidosis with
polyneuropathy: avoiding misdiagnosis of a treatable hereditary
neuropathy. J Neurol Neurosurg
Psychiatry.
2017;88(5):457-458.
4. ClinicalTrials.gov [Internet].
CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of
Eplontersen (Formerly Known as, IONIS-TTR-LRx and AKCEA-TTR-LRx) in
Participants With Transthyretin-Mediated Amyloid Cardiomyopathy
(ATTR CM) [cited 18 June 2022]. Available from: https://clinicaltrials.gov/ct2/show/NCT04136171.
5. ClinicalTrials.gov [Internet].
NEURO-TTRansform: A Study to Evaluate the Efficacy and Safety of
Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and
AKCEA-TTR-LRx) in Participants With Hereditary
Transthyretin-Mediated Amyloid Polyneuropathy [cited 18 June 2022].
Available from: https://clinicaltrials.gov/ct2/show/NCT04136184.
6. Viney N, et al. Ligand conjugated
antisense oligonucleotide for the treatment of transthyretin
amyloidosis: preclinical and phase 1 data. ESC Heart
Failure.
2020;8(1):652-661.
7.
Gertz M, et al. Avoiding misdiagnosis: expert consensus
recommendations for the suspicion and diagnosis of transthyretin
amyloidosis for the general practitioner. BMC Fam Pract.
220;21(1):198.
8.
Rintell D, et al. Patient and family experience with transthyretin
amyloid cardiomyopathy (ATTR-CM and polyneuropathy (ATTR-PN)
amyloidosis: results of two focus groups. Orphanet J Rare Dis.
2021;16:7.
9.
Lauppe RE, et al. Nationwide prevalence and characteristics of
transthyretin amyloid cardiomyopathy in Sweden. Open Heart.
2021;8(2):e001755.
10. Ionis Pharmaceuticals, Inc., [Internet].
Annual Report, 2022 [cited 18 June 2022]. Available
from: https://ir.ionispharma.com/static-files/285deeed-625c-4d5b-beff-8490f93622ce.
11. Vinik
EJ, et al. Norfolk QOL-DN: validation of a patient reported outcome
measure in transthyretin familial amyloid
polyneuropathy. J Peripher Nerv
Syst. 2014;19(2):104-114.
Adrian Kemp
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:
21 June 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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