Wainua (eplontersen) / Ionis, AstraZeneca - LARVOL DELTA

EPIC-ATTR: A Study to Evaluate the Effect of Eplontersen on the Transthyretin Reduction and Long-term Safety in Chinese Subjects With Transthyretin Amyloid Cardiomyopathy (clinicaltrials.gov) - P3 | N=64 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Mar 2025 ➔ Apr 2026

Trial primary completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

eplontersen (Wainzua) is accepted for use within NHSScotland (Scottish Medicines Consortium) - "Indication under review: for the treatment of hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis) in adult patients with Stage 1 and 2 polyneuropathy. Eplontersen offers an additional treatment choice of transthyretin (TTR) gene silencer for this indication. Another TTR gene silencer was accepted for use under the ultra-orphan process."

Reimbursement • Amyloidosis

IMPROVEMENT IN MEASURES OF QUALITY OF LIFE AMONG PATIENTS RECEIVING TARGETTED THERAPY FOR ATTR AMYLOIDOSIS: A META-ANALYSIS OF DATA FROM RANDOMIZED CONTROLLED TRIALS - Shubhashis Saha (ACC 2025) - "Background: Novel drugs like patisiran, vutrisiran, tafamidis, acoramidis, eplontersen, and inotersen reduce the synthesis and deposition of TTR amyloid fibrils in patients with cardiac amyloidosis. Contemporary drugs for cardiac amyloidosis improved quality of life and 6MWT, while having a good safety profile. Although they are usually classified as secondary outcomes in many clinical trials, these improvements would be more relevant to the patients in short to medium term."

HEOR • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

LACK OF IMPROVEMENT IN CARDIAC FUNCTION AMONG PATIENTS RECEIVING TARGETTED THERAPY FOR ATTR AMYLOIDOSIS: A META-ANALYSIS OF DATA FROM RANDOMIZED CONTROLLED TRIALS - Revati Varma (ACC 2025) - "Background: Novel drugs like patisiran, vutrisiran, tafamidis, acoramidis, eplontersen, and inotersen reduce the synthesis and deposition of TTR amyloid fibrils in patients with cardiac amyloidosis (CA). Contemporary drugs for CA did not result in changes in the cardiac structure on echocardiographic parameters while having a good safety profile."

Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

GEOGRAPHIC DISPARITIES IN CARDIAC AMYLOIDOSIS PRESCRIBING PATTERNS: INSIGHTS FROM EPIC COSMOS - Mirza S. Khan (ACC 2025) - "Medications included novel amyloid therapies tafamidis, vutrisiran, patisiran, eplontersen, inotersen and diflunisal. The highest prescription rates for cardiac amyloidosis therapies were in the Northeast U.S., known to have a high density of dedicated amyloidosis centers. Our findings underscore the need for efforts to improve recognition and diagnosis of cardiac amyloidosis and improve treatment access in underserved regions."

Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Congestive Heart Failure • Heart Failure

Hope on the horizon: FDA approves eplontersen for hereditary transthyretin-mediated amyloidosis. (PubMed, Ann Med Surg (Lond)) - No abstract available

FDA event • Journal • Amyloidosis

WAINZUA (eplontersen) approved in the EU for the treatment of hereditary transthyretin-mediated amyloidosis in adults with stage 1 or stage 2 polyneuropathy (Businesswire) - "Ionis Pharmaceuticals, Inc...announced today that Ionis and AstraZeneca’s WAINZUA (eplontersen) has been approved in the European Union (EU) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, commonly referred to as hATTR-PN or ATTRv-PN. WAINZUA is the only approved medicine in the EU for the treatment of ATTRv-PN that can be self-administered monthly via an auto-injector...The approval is based on the positive NEURO-TTRansform Phase 3 trial which showed that through 66 weeks, patients treated with WAINZUA demonstrated consistent and sustained benefit on the co-primary endpoints of serum transthyretin (TTR) concentration and neuropathy impairment measured by modified Neuropathy Impairment Score +7 (mNIS+7), and key secondary endpoint of quality of life (QoL) on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) versus external placebo."

EMA approval • Amyloidosis • CNS Disorders

RNAi-based Therapies for Hereditary Transthyretin Amyloidosis with Polyneuropathy: A Meta-analysis of Randomized Clinical Trials (AAN 2025) - "Subgroup analysis is performed based on individual RNAi drugs.We included 5 trials involving 595 patients received Patisiran, Eplontersen, Inotersen, or Vutisiran. Our results suggest that RNAi-based therapies are promising for hATTR with polyneuropathy treatment, showing improvements in neurological function, quality of life, and an acceptable safety profile. However, evidence is limited, with heterogeneity in long-term safety and effectiveness across studies. Further randomized trials are needed to clarify the role of RNAi therapeutics and optimize patient outcomes."

Retrospective data • Amyloidosis • Cardiac Amyloidosis • Genetic Disorders • Pain

Ionis reports fourth quarter and full year 2024 financial results (Businesswire) - "'Over the next three years, we expect three more independent launches, including donidalorsen later this year for hereditary angioedema and olezarsen for severe hypertriglyceridemia in 2026, pending Phase 3 results in the second half of this year. Additionally, our partners are on track to launch four Ionis-discovered medicines over the same time period, including several that address broad patient populations'...WAINUA...Generated sales of $85 million resulting in royalty revenue of $20 million in the year ended December 31, 2024...SPINRAZA...generated global sales of $1.6 billion resulting in royalty revenue of $216 million in year ended December 31, 2024...Higher dose nusinersen under regulatory review in U.S. (PDUFA date of September 22, 2025) and EU. QALSODY (tofersen) for the treatment of SOD1-ALS generated global sales of $32 million resulting in royalty revenue of $4 million in the year ended December 31, 2024."

Launch • P3 data • PDUFA • Sales • Amyloidosis • Amyotrophic Lateral Sclerosis • Cardiovascular • Genetic Disorders • Hereditary Angioedema • Muscular Atrophy • Severe Hypertriglyceridemia

New therapies to treat cardiac amyloidosis. (PubMed, Curr Opin Cardiol) - "The therapeutic landscape for ATTR-CM and AL-CM is rapidly evolving, driven by novel therapies targeting diverse mechanisms. Ongoing clinical trials promise to further refine the standard of care and improve outcomes for patients with cardiac amyloidosis."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

Ionis enters new chapter in 2025 as commercial-stage biotech with multiple independent product launches anticipated and continued late-stage pipeline momentum (PRNewswire) - "Continue progress with WAINUA (eplontersen), Ionis' first U.S. co-commercialized medicine in collaboration with AstraZeneca...Continuing the fully enrolled, landmark CARDIO-TTRansform trial in ATTR cardiomyopathy, with data expected in the second half of 2026...Phase 2 data for ION464 (SNCA) in multiple system atrophy."

P2 data • P3 data • Amyloidosis • Multiple System Atrophy

ATTR-CM: CARDIO-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 Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM) (clinicaltrials.gov) - P3 | N=1438 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Trial completion date: Nov 2025 ➔ Aug 2026 | Trial primary completion date: Jun 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Disease-modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications. (PubMed, Pharmacotherapy) - "Tafamidis and acoramidis are currently approved for ATTR-CM while vutrisiran approval for ATTR-CM may be forthcoming...However, several unmet needs exist including the lack of cost-effectiveness due to the extremely high acquisition costs of these medications. Disease-modifying medications approved and in development to treat ATTR-CM offer hope for patients with this disease, but their lack of affordability is the biggest barrier to their use."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Rare Diseases

RNA Interference Therapeutics for Hereditary Transthyretin-Mediated Amyloidosis with Neuropathy: A Systematic Review (ASH 2024) - "Currently, limited treatment options are available for ATTRv, which include orthotopic liver transplantation and transthyretin tetramer stabilizers (tafamidis or diflunisal)...The most common cause of death reported was cardiac failure.Conclusion : RNA interference therapies, including Eplontersen, Inotersen, Vutrisiran, and Patisiran, have demonstrated significant benefits in enhancing the quality of life for patients with ATTRv and associated polyneuropathy...While RNAi therapies offer substantial symptomatic relief, vigilant surveillance for side effects is crucial to optimize patient outcomes and ensure safety. Further studies, including comparative studies, are essential to establish therapeutic protocols and ensure improved quality of life for patients with ATTRv."

Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Diabetic Neuropathy • Glomerulonephritis • Heart Failure • Hematological Disorders • Hepatology • Lupus Nephritis • Nephrology • Pain • Renal Disease • Thrombocytopenia

Ionis reports third quarter 2024 financial results (PRNewswire) - "WAINUA (WAINZUA in Europe) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) achieved multiple commercial and regulatory milestones...Generated sales of $23 million and $44 million resulting in royalty revenue of $5 million and $10 million in the three and nine months ended September 30, 2024, respectively...IONIS-MAPTRx (BIIB080) enrollment complete in Phase 2 CELIA study in patients with early Alzheimer's disease (AD); data expected in 2026."

P2 data • Sales • Alzheimer's Disease • Amyloidosis • Cardiovascular • CNS Disorders

Effects of eplontersen on symptoms of autonomic neuropathy in hereditary transthyretin-mediated amyloidosis: secondary analysis from the NEURO-TTRansform trial. (PubMed, Amyloid) - "Improvements with eplontersen versus placebo were observed up to Week 66 in autonomic components of mNIS+7, Norfolk QoL-DN, NSC, and mBMI; eplontersen results were sustained up to Week 85, including improvements in COMPASS-31 (Week 81). Eplontersen demonstrated benefit across multiple measures of autonomic impairment known to progress rapidly and negatively impact QoL without treatment, without deterioration in nutritional status."

Journal • Amyloidosis • Cardiac Amyloidosis • Diabetic Neuropathy • Pain

Estimating Meaningful Differences in Measures of Neuropathic Impairment, Health-Related Quality of Life, and Nutritional Status in Patients With Hereditary Transthyretin Amyloidosis. (PubMed, Muscle Nerve) - "Eplontersen demonstrated a clinically meaningful effect on neuropathic impairment, QoL, and nutritional status. Such estimates have implications for clinical practice and trials."

HEOR • Journal • Amyloidosis • Cardiac Amyloidosis • Diabetic Neuropathy • Pain

NICE Recommends AstraZeneca’s Wainzua for ATTRv Amyloidosis, Citing Cost Savings Over Amvuttra (NAVLIN DAILY) - "The company provided clinical data from the NEURO-TTRansform trial, a Phase III, multicenter, open-label, randomized study. Evidence suggests Wainzua is more effective than placebo in reducing transthyretin blood levels and extends the time before polyneuropathy worsens. Although no direct comparisons exist between Wainzua and vutrisiran, an indirect analysis indicates comparable efficacy. Additionally, a cost comparison shows that Wainzua is cost-saving compared to Amvuttra, leading to its recommendation."

NICE • Amyloidosis • CNS Disorders

A Study to Assess the PK, PD, Safety and Tolerability of Eplontersen in Healthy Chinese Volunteers (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyloidosis

A Study to Assess the PK, PD, Safety and Tolerability of Eplontersen in Healthy Chinese Volunteers (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Amyloidosis

Busy 12 months for the FDA in the #transthyretin #amyloidosis space 12/2023 - acoramidis NDA for ATTR-CM submitted 12/2023 - eplontersen approved for vATTR polyneuropathy 10/2024 - vutrisiran sNDA submitted for ATTR-CM with a priority review voucher 11/2024 - PDUFA date (expected FDA decision date) for acoramidis in ATTR-CM This tremendous progress in the ATTR space is happening as we… (LinkedIn)

AstraZeneca receives MHRA approval for Wainzua in rare nerve disease ATTRv-PN (PMLive) - "AstraZeneca (AZ) has received approval from the Medicines and Healthcare products Regulatory Agency (MHRA) for the use of Wainzua (eplontersen) in adults with the rare progressive condition hereditary transthyretin amyloidosis (ATTRv). The drug has been specifically authorised for use in patients with polyneuropathy (PN), which is damage to multiple nerves outside of the brain and central nervous system...The MHRA’s decision on the therapy was supported by positive results from the late-stage NEURO-TTRansform trial, in which Wainzua-treated ATTRv patients experienced greater reductions in TTR levels and less worsening of the disease from baseline compared to an external placebo group."

MHRA approval • Amyloidosis • CNS Disorders

Wainzua (eplontersen) recommended for approval in the EU by CHMP for the treatment of adult patients with polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (AstraZeneca Press Release) - "AstraZeneca and Ionis’ Wainzua (eplontersen) has been recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) in the European Union (EU) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, commonly referred to as hATTR-PN or ATTRv-PN. If approved by the European Commission, Wainzua will be the only approved medicine in the EU for the treatment of ATTRv-PN that can be self-administered monthly via an auto-injector...The CHMP based its opinion on the positive NEURO-TTRansform Phase III trial..."

CHMP • Amyloidosis • CNS Disorders

ATTRv Neuropathy (ICNMD 2024) - "Transthyretin protein stabilisers diflunisal, tafamidis and acoramidis, can delay the progression of the disease, if treated early in the course. Additionally, TTR gene silencing medications, patisiran and inotersen, and second-generation silencers vutrisiran and eplontersen, have resulted in up to 80% reduction in TTR production leading to stabilisation or improvement of peripheral neuropathy and cardiac dysfunction, as well as improvement in quality of life and functional outcomes...Furthermore, current management strategies do not modify occular or CNS TTR production, and as such late occurrence of the disease in these compartments is becoming more prevalent. As such, novel treatment strategies or optimised CNS and ocular penetrance of existing treatments are required to treat these emerging manifestations."

Amyloidosis • Cardiac Amyloidosis • Musculoskeletal Pain • Pain

Kidney Function And Proteinuria With Eplontersen Treatment For Hereditary Transthyretin Amyloidosis (HFSA 2024) - P2/3, P3 | "Kidney function was stable over time with eplontersen and placebo treatment, and the incidence of new CKD and nephrotic range proteinuria was similar in both treatment groups. Additional assessments of kidney function in participants treated with eplontersen will be performed in the ongoing CARDIO-‍TTRansform trial."

Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Chronic Kidney Disease • Nephrology • Pain • Renal Disease