Reading, UK, 13 December 2024 – The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of acoramidis, a selective small molecule, orally administered transthyretin (TTR) stabiliser, in the European Union (EU).1 The compound is recommended for approval in adults with wild-type or hereditary transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive disease that presents as an infiltrative, restrictive cardiomyopathy resulting in heart failure. In vitro, acoramidis demonstrated ≥90% TTR stabilisation3 and in the Phase III study ATTRibute-CM, acoramidis has been shown to demonstrate benefit on the primary hierarchical endpoint of all-cause mortality, cardiovascular-related hospitalisation, change from baseline in NT-proBNP and 6-minute walk distance at month 30.2 The overall incidence of adverse events was similar in the acoramidis group and the placebo group.2
Following the positive CHMP opinion, Bayer will submit a Marketing Authorisation Application (MAA) to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for the use of acoramidis in adult patients with wild-type or hereditary ATTR-CM in the UK.
The positive CHMP opinion for acoramidis and the subsequent UK submission to the MHRA are based on the ATTRibute-CM Phase III study results. The study investigated the efficacy and safety profile of acoramidis given twice daily compared to placebo, in adults with wild-type or hereditary ATTR-CM.2 The ATTRibute-CM Phase III study met its primary hierarchical endpoints, which include all-cause mortality, cardiovascular hospitalisations, change from baseline in NT-proBNP and 6-minute walk distance at month 30.2
“ATTR-CM is often delayed in its recognition or is misdiagnosed, which can have a negative impact on patients’ outcomes. It is a condition that progresses in the absence of treatment and is ultimately fatal,4-6” said Julian Gillmore, Professor of Medicine, University College London (UCL) Centre for Amyloidosis, UK. “The CHMP's positive opinion offers hope to individuals living with ATTR-CM. We are encouraged by the prospect of additional treatment to slow the progression of symptoms and improve outcomes in patients with ATTR-CM.”
“Patients living with ATTR-CM often see a decline in their quality of life due to the physical and functional challenges posed by their condition. There is a clear need for continued innovation and further options for patients affected,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer. “This positive recommendation from the CHMP represents a significant milestone in the fight against this life-threatening heart disease.”
The final decision from the European Commission (EC) on the marketing authorisation is expected in the coming months. Acoramidis was recently approved by the Food and Drug Administration (FDA) for the U.S..7 BridgeBio holds the marketing rights for acoramidis in the U.S., while Bayer holds the exclusive marketing rights for the product in Europe.
Since March 2024, Bayer and BridgeBio, have pursued a collaboration for acoramidis. This partnership leverages Bayer’s long legacy of expertise in cardiovascular disease and its established European cardiovascular infrastructure paired with BridgeBio’s leadership in the emerging field of ATTR-CM.
ENDS
Bayer Media Contact:
Veronica Yao, +44 (0) 7870 485 926
Email: veronica.yao@bayer.com
Notes to Editors
About ATTR-CM
Transthyretin amyloid cardiomyopathy (ATTR-CM) is progressive and can be a fatal disease in adults, characterised by the deposition of abnormal protein in the heart as well as other organs and tissues. It occurs when a tetrameric protein called transthyretin (TTR) becomes unstable, caused by an inherited mutation in the TTR gene or due to aging, and dissociates into monomers. These monomers can misfold, aggregate, and form amyloid fibrils that deposit in the heart muscle, leading eventually to heart failure. The disease is often diagnosed late, when the accumulation of amyloid in the heart has already occurred, and patients are symptomatic.8 Once diagnosed, ATTR-CM patients have a median survival of approximately 3-5 years if left untreated.9
About acoramidis and the Phase III study results
Acoramidis is an investigational, orally administered, selective small molecule stabiliser of transthyretin (TTR). Acoramidis was designed to mimic a naturally occurring "protective mutation” of the TTR gene (T119M) that targets the destabilisation of the native TTR tetramer which causes ATTR-CM. In vitro, acoramidis demonstrated ≥90% TTR stabilisation3 and in the Phase III study ATTRibute-CM, acoramidis has been shown to demonstrate benefit on the primary efficacy endpoint at month 30.2
In the ATTRibute-CM Phase III study, acoramidis met the primary endpoint. The primary objective of the ATTRibute-CM Phase III study was to establish superiority of acoramidis versus placebo on a hierarchical endpoint that included all-cause mortality (ACM), cumulative frequency of cardiovascular-related hospitalisations (CVH), change from baseline in NT-proBNP and 6-minute walk distance at month 30.2
A total of 632 patients underwent randomisation (421 to the acoramidis group and 211 to the placebo group) in the study. When compared to placebo, acoramidis twice daily demonstrated an early and sustained clinical benefit on the primary hierarchical endpoint of all-cause mortality, cardiovascular hospitalisation, change from baseline in NT-proBNP, 6-minute walk distance in adults with ATTR-CM through month 30 (p<0.001)2. Key secondary outcomes relating to patient quality of life included the change from baseline until month 30 in the 6-minute walk distance and KCCQ-OS
(Kansas City Cardiomyopathy Questionnaire – Overall Summary) score.2
Acoramidis was generally well-tolerated. The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively).2
About Bayer’s Commitment in Cardiovascular Diseases
Bayer is a leader in cardiology and is advancing a portfolio of innovative treatments in cardiovascular (CV) diseases of high unmet medical need. The strategy is to transform its portfolio into precision cardiology to support patients living with CVD, addressing the high CV disease burden as well as driving the long-term growth. Bayer’s portfolio already includes several investigational products and compounds in various stages of preclinical and clinical development.
About Bayer
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.co.uk.
Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.co.uk. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
References:
1. Positive recommendations on new medicines. Meeting highlights form the CHMP 9-12 December 2024. Available at: https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-9-12-december-2024#positive-recommendations-on-new-medicines-72070. Last accessed: December 2024.
2. Gillmore JD, Judge DP, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs S, Grogan M, Hanna M, Hoffman J, Masri A, Maurer MS. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. New England Journal of Medicine. 2024 Jan 11;390(2):132-42.
3. Miller M, Pal A, Albusairi W, Joo H, Pappas B, Haque Tuhin MT, Liang D, Jampala R, Liu F, Khan J, Faaij M. Enthalpy-driven stabilization of transthyretin by AG10 mimics a naturally occurring genetic variant that protects from transthyretin amyloidosis. Journal of medicinal chemistry. 2018 Aug 22;61(17):7862-76.
4. Rozenbaum MH, et al. Impact of delayed diagnosis and misdiagnosis for patients with transthyretin amyloid cardiomyopathy (ATTR-CM): a targeted literature review. Cardiology and therapy. 2021;10:141-59.
5. Mallus MT and Rizzello V. Treatment of amyloidosis: present and future. 2023;21;25(Suppl B):B99-B103.
6. Jain A, Zahra F. Transthyretin Amyloid Cardiomyopathy (ATTR-CM). Updated 27 April 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK574531/ Last accessed: December 2024.
7. Attruby™ (acoramidis), a Near Complete TTR Stabilizer (≥90%), approved by FDA to Reduce Cardiovascular Death and Cardiovascular-related Hospitalization in ATTR-CM Patients
8. Jain A, Zahra F. Transthyretin Amyloid Cardiomyopathy (ATTR-CM) [Updated 2023 Apr 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK574531/ Last accessed: December 2024.
9. Witteles et al. Screening for Transthyretin Amyloid Cardiomyopathy in Everyday Practice. JACC: Heart Failure. https://doi.org/10.1016/j.jchf.2019.04.010
RP-M_ACR-GB-0033 / December 2024