ADULT PATIENTS IN SCOTLAND WITH HEREDITARY TRANSTHYRETIN-MEDIATED AMYLOIDOSIS WITH STAGE 1 AND 2 POLYNEUROPATHY CAN NOW ACCESS ASTRAZENCA’S WAINZUA™▼(EPLONTERSEN)

ADULT PATIENTS IN SCOTLAND WITH HEREDITARY TRANTHYRETIN-MEDIATED AMYLOIDOSIS WITH STAGE 1 AND 2 POLYNEUROPATHY CAN NOW ACCESS ASTRAZENCA’s WAINZUA™▼(EPLONTERSEN)

• Eligible adults living with stage 1 and 2 polyneuropathy in hereditary transthyretin-mediated amyloidosis (ATTRv-PN) across Scotland can now access eplontersen therapy following acceptance from the Scottish Medicines Consortium (SMC).[i]
• Results from the three co-primary endpoints in the NEURO-TTRansform Phase III clinical trial showed that at week 65/66, from baseline versus external placebo, treatment with eplontersen decreased transthyretin (TTR) serum concentration, reduced progression of neuropathy impairment, and improved patients' quality of life.[ii]
• Eplontersen is the first and only self administered monthly pre-filled pen to be accepted in Scotland for ATTRv-PN.¹ This means patients can choose to be treated in clinic, or at home, following training from a qualified healthcare professional.¹

London, UK, Monday 7 April 2025 – Today, AstraZeneca announced that the Scottish Medicines Consortium (SMC) has accepted Wainzua (eplontersen) for use within NHS Scotland for the treatment of hereditary (v) transthyretin-mediated amyloidosis (ATTRv amyloidosis) in adult patients with stage 1 and 2 polyneuropathy.¹

This decision from the SMC was achieved through the organisations abbreviated submission process – allowing faster patient access to new medicines due to a streamlined review process.[iii] Acceptance from the SMC further reinforces AstraZeneca’s leadership and commitment to advancing scientific innovation in amyloidosis to improve the lives of patients impacted by this serious disease.

Vince Nicholas, Trustee & Treasurer, Amyloidosis UK and ATTRv patient, said: “Living with hereditary transthyretin-mediated amyloidosis presents significant daily challenges for patients and their families. From progressive nerve damage to mobility difficulties, the burden of this rare disease is profound and often misunderstood. Today’s decision represents a positive step forward for patients and the management of this condition in Scotland.”

ATTRv-PN is a rare, serious, and progressive disorder caused by a mutation in the transthyretin (TTR) gene, which is responsible for the production of the TTR protein in the liver.[iv]^,[v] This mutation causes the TTR protein to misfold leading to the accumulation of amyloid fibrils which damage peripheral nerves throughout the body.[vi]^,[vii]^,[viii] It is frequently under-recognised due to its non-specfic and heterogeneous clinical manifestations.^6,[ix]^,[x]

As ATTRv-PN progresses, complications can lead to painful polyneuropathy in the hands and feet, motor disability including difficulty walking or falls, and gastrointestinal abnormalities, within 5 years.^6,[xi]^,[xii] The prognosis of ATTRv-PN is poor, typically resulting in death within a decade, without treatment.^12,[xiii] Eplontersen works by lowering the amount of TTR protein produced at its source in the liver, resulting in fewer amyloid deposits building up throughout the body.²

 The acceptance from the SMC is based on results from the NEURO-TTRansform Phase III clinical trial which enrolled 168 patients with Coutinho stage 1 or 2 ATTRv-PN (144 assigned to eplontersen and 24 treated with inotersen as a reference group) and included 60 patients categorised as external placebo controls from NEURO-TTR, an inotersen trial.² At week 65, in a co-primary endpoint of the trial, eplontersen achieved a least squares (LS) mean reduction of 81.7% in serum TTR protein levels from baseline compared to an 11.2% reduction from baseline in the external placebo group (difference, -70.4% [95% CI, -75.2% to -65.7%]; p<0.001].² Results showed that eplontersen reduced serum TTR protein levels as early as week 5.²

Tom Keith-Roach, President, AstraZeneca UK, said: “We are delighted that the SMC has accepted eplontersen for use within NHS Scotland for the treatment of ATTRv in adults with stage 1 and 2 polyneuropathy. This decision marks a step forward for eligible patients in Scotland, who now have another treatment option for this progressive and debilitating condition, with additional flexibility and choice around being treated in clinic or at home.”

At week 66, in the other co-primary endpoints of the NEURO-TTRansform trial, the modified Neuropathy Impairment Score +7 (mNIS+7) showed that the progression of neuropathy impairment from baseline vs external placebo had significantly reduced (0.3 point LS mean increase vs 25.1 point increase; difference, −24.8 [95% CI, −31.0 to −18.6; p<0.001).² Additionally, there was significantly improved quality of life from baseline vs external placebo as measured by the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) (−5.5 point LS mean decrease vs 14.2 point increase; difference, −19.7 [95% CI, −25.6 to −13.8]; p<0.001).² QoL-DN is a patient-reported assessment that evaluates subjective experience.[xiv]

Eplontersen was generally well tolerated and treatment-emergent adverse events (TEAE) were mild in 51%, moderate in 37% and severe in 9% of patients.² The incidence of treatment discontinuation due to TEAEs was low (4%).² The most frequent adverse reactions during treatment with eplontersen observed in ≥5% of patients were decreased vitamin A, injection site reactions, vomiting and proteinuria.[xv]

– ENDS –

CONTACTS

UK Media Enquiries

Georgia Clarke, AstraZeneca: 07586 798507 / georgia.clarke@astrazeneca.com

Lucie Foster, Edelman: 07891 869948 / lucie.foster@edelman.com 

NOTES TO EDITORS

About eplontersen

Eplontersen is a ligand-conjugated antisense oligonucleotide (LICA) medicine that inhibits the production of transthyretin, or TTR protein.¹⁵ Eplontersen, which is targeted to the liver by a ligand containing three N-acetyl galactosamine residues, binds to wild-type and variant TTR mRNA, thus reducing the levels of circulating TTR protein and amyloid deposition.¹⁵ Eplontersen provides eligible patients and caregivers with the option of once-monthly dosing, using a self-administered, subcutaneous, pre-filled pen.¹⁵ The first injection administered by the patient or caregiver is given under the supervision of a qualified healthcare professional.¹⁵ Patients and/or caregivers should be properly trained in administering eplontersen subcutaneously.¹⁵

For complete information about eplontersen, the summary of product characteristics (SmPC), including a full list of side effects and adverse reactions, is available here: https://www.medicines.org.uk/emc/product/100312/smpc

About NEURO-TTRansform

NEURO-TTRansform is a global, open-label, randomised trial evaluating the efficacy and safety of eplontersen in patients with ATTRv-PN.¹⁴ The trial enrolled adult patients with ATTRv-PN stage 1 or stage 2 and compared to the external placebo group from the TEGSEDI^® (inotersen) NEURO-TTR registrational trial that Ionis completed in 2017.¹⁴

The final analysis comparing eplontersen to external placebo was completed at week 66 and all patients were followed on treatment until week 85, when they had the option to transition into an open-label extension study which is still ongoing.¹⁴ The 66-week analysis evaluated percent change from baseline in serum TTR concentration, changes in the mNIS+7 and Norfolk-QoL-DN in the eplontersen group versus an external placebo group.¹⁴ The mNIS+7 uses highly standardised, quantitative and referenced assessments to quantify muscle weakness, muscle stretch reflexes, sensory loss and autonomic impairment.¹⁴ The Norfolk QoL-DN is a patient-reported questionnaire capturing neuropathy-related QoL.¹⁴

About ATTRv-PN

ATTRv-PN is a progressive systemic disease caused by a genetic mutation, resulting in misfolded TTR protein and accumulation as amyloid fibrils in the peripheral nerves.^6,9,10 TTR protein builds up as fibrils in the peripheral nerves and interferes with the normal functions of these tissues.^6,8,[xvi] As the TTR protein fibrils accumulate, more tissue damage occurs and the disease worsens, resulting in poor QoL and eventually death.⁶

Diagnosis is often a lengthy process because symptoms of ATTRv are commonly misattributed to other conditions (gastrointestinal, musculoskeletal, polyneuropathy).⁶ It can often take many visits to different types of physicians before a correct diagnosis and treatment are obtained.⁹

The prevalence of hereditary ATTR (ATTRv) amyloidosis is estimated to be less than 1 in 100,000 people in the general European population.[xvii] In the UK there are thought to be around 230 people with this disease.[xviii]

ATTRv is classified into 4 stages:¹⁷

• Stage 0: asymptomatic disease
• Stage 1: patients have mild polyneuropathy symptoms
• Stage 2: patients have moderate symptoms and require assistance to walk
• Stage 3: patients have severe symptoms and require a wheelchair or are bedbound

The effects and complications of the disease can lead to death within 5 to 15 years of symptoms developing.¹⁷

About AstraZeneca

AstraZeneca 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. AstraZeneca operates in over 100 countries and its medicines are used by millions of patients worldwide.

With a proud 100-year heritage in advancing UK science, today AstraZeneca is the UK’s leading biopharmaceutical company. The company is based in five different locations across the UK, with its global headquarters in Cambridge. In the UK, around 8,700 employees work in research and development, manufacturing, supply, sales, and marketing. We supply around 36 different medicines to the NHS.

For more information, please visit www.astrazeneca.co.uk and follow us on X @AstraZenecaUK.

References

[i] Scottish Medicines Consortium. Eplontersen solution for injection in pre-filled pen (Wainzua^®): Detailed advice document SMC2755 – published 7 April 2025.

[ii] Coelho T, et al. Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy. JAMA. 2023 Oct 17;330(15):1448-1458. doi: 10.1001/jama.2023.18688

[iii] Scottish Medicine Consortium. Abbreviated Submissions. Available at: https://scottishmedicines.org.uk/how-we-decide/abbreviated-submissions/. Last accessed: April 2025.

[iv] Lamb YN, et al.Tafamidis: A Review in Transthyretin Amyloidosis with Polyneuropathy. Drugs. 2019;79(8):863-874.

[v] Marcia Almedia L, et al. A Narrative Review of the Role of Transthyretin in Health and Disease. Neurol Ther. 2020;9(2):395-402.

[vi] Nativi-Nicolau JN, et al. Screening for ATTR amyloidosis in the clinic: overlapping disorders, misdiagnosis, and multiorgan awareness. Heart Fail Rev. 2022;27:785-793.

[vii] Ando Y, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013;8:31

[viii] Tschöpe C, et al. Treatment of Transthyretin Amyloid Cardiomyopathy: The Current Options, the Future, and the Challenges. J Clin Med. 2022;11(8):2148

[ix] Gertz M, et al. Avoiding misdiagnosis: expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner. BMC Fam Pract. 2020;21(1):198.

[x] Adams D, et al. Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy. J Neurol. 2021;268(6):2109-2122.

[xi] 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

[xii] Luigetti M, et al. Diagnosis and Treatment of Hereditary Transthyretin Amyloidosis (hATTR) Polyneuropathy: Current Perspectives on Improving Patient Care. Ther Clin Risk Manag. 2020;16: 109–123.

[xiii] Samjoo, I.A et al. The impact of clinical heterogeneity on conducting network meta-analyses in transthyretin amyloidosis with polyneuropathy. Current Medical Research and Opinion. 2020;36(5):799-808.

[xiv] 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.

[xv] Electronic Medicines Compendium (emc). Wainzua 45 mg/0.8 ml Solution for injection – Summary of Product Characteristics (SmPC). Available at: https://www.medicines.org.uk/emc/product/100312/smpc. Last accessed: April 2025.

[xvi] Ioannou A, et al. Targeting and Gene Editing Strategies for Transthyretin Amyloidosis. BioDrugs. 2023 Mar;37(2):127-142. doi: 10.1007/s40259-023-00577-7. Epub 2023 Feb 16

[xvii] National Institute for Health and Care Excellence (NICE). Health Technology Evaluation Vutrisiran for treating hereditary transthyretin-related amyloidosis. Available at: https://www.nice.org.uk/guidance/ta868/documents/draft-scope-post-referral. Last accessed: April 2025.

[xviii] National Institute for Health and Care Excellence (NICE). Health Technology Evaluation Eplontersen for treating polyneuropathy caused by hereditary transthyretin amyloidosis. Available at: https://www.nice.org.uk/guidance/gid-ta11392/documents/draft-scope-post-referral. Last accessed: April 2025.