A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of Acoramidis for Transthyretin Amyloidosis Prevention in the Young (ACT-EARLY Trial)

Transthyretin amyloidosis (ATTR) is a disease where the normally occurring transthyretin (TTR) protein falls apart and forms amyloid, a sticky plaque- like substance that accumulates in different organs in the body and can cause damage to the organ. There are two ways that the TTR protein can fall apart. One way occurs as a person ages, where the normal TTR protein can fall apart and form amyloid that may no longer be sufficiently cleared by the body. This type of ATTR is known as wild-type ATTR (ATTRwt). The other way occurs when a person inherits a defective TTR gene that causes the TTR protein to spontaneously fall apart. This form of the disease is known as variant ATTR (ATTRv) and can be detected in adults by a genetic test of their TTR gene before they age.
Amyloid build-up in the heart causes the heart wall to become thick and stiff and can result in heart failure and even death. Accumulation of TTR amyloid in the heart is known as transthyretin amyloid cardiomyopathy or ATTR-CM. Amyloid can also deposit in the nerve tissues leading to nerve problems. Accumulation of TTR in the nerves is known as transthyretin amyloid polyneuropathy or ATTR-PN.
Acoramidis is an experimental drug designed to bind tightly to TTR in the blood and stabilize its structure, so it does not form the harmful amyloid plaques that can cause damage to organs.
This study is intended to determine if treatment with acoramidis in participants with ATTRv who have not yet developed any symptoms of disease can prevent or delay the development of ATTR-CM or ATTR-PN disease. If adults with an inherited defective TTR gene are treated early before any of the symptoms of disease have developed, it may be possible to delay the onset or prevent the disease entirely.

Start Date01 Apr 2025

Sponsor / Collaborator

Eidos Therapeutics, Inc.

ISRCTN11628974

/ CompletedPhase 1

A multiple dose study to evaluate the pharmacokinetics of an acoramidis (AG10) modified release tablet formulation in healthy subjects

Start Date30 Aug 2022

Sponsor / Collaborator

Eidos Therapeutics, Inc.

EUCTR2020-005643-22-BE

/ Not yet recruitingPhase 3

An Open-Label Extension and Safety Monitoring Study of Acoramidis (AG10) in Participants with Symptomatic Transthyretin Amyloid Cardiomyopathy Who Completed the Phase 3 ATTRibute-CM Trial (AG10-301)

Start Date07 Jul 2022

Sponsor / Collaborator

Eidos Therapeutics, Inc.

100 Clinical Results associated with Acoramidis

100 Translational Medicine associated with Acoramidis

100 Patents (Medical) associated with Acoramidis

Literatures (Medical) associated with Acoramidis

04 Mar 2025·CIRCULATION

Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial

Article

Author: Maurer, Mathew S. ; Sinha, Uma ; Shah, Keyur ; Hvitfeldt Poulsen, Steen ; Cao, Xiaofan ; Soman, Prem ; Pecoraro, Maria Lucia ; Nativi-Nicolau, Jose ; Obici, Laura ; Gillmore, Julian D. ; Grodin, Justin L. ; Tamby, Jean-François ; García-Pavía, Pablo ; Cappelli, Francesco ; Judge, Daniel P. ; Fontana, Marianna ; Katz, Leonid ; Sarswat, Nitasha ; Wang, Kevin ; Grogan, Martha ; Alexander, Kevin M. ; Ambardekar, Amrut V. ; Fox, Jonathan C. ; Hanna, Mazen ; Lystig, Ted ; Masri, Ahmad

BACKGROUND::

In the phase 3 randomized controlled study ATTRibute-CM (Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy), acoramidis, a transthyretin stabilizer, demonstrated significant efficacy on the primary end point. Participants with transthyretin amyloid cardiomyopathy who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report the efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE.

METHODS::

Participants who previously received acoramidis through month 30 in ATTRibute-CM continued to receive it (continuous acoramidis), and those who received placebo through month 30 were switched to acoramidis (placebo to acoramidis). Participants who received concomitant tafamidis in ATTRibute-CM were required to discontinue it to be eligible to enroll in the OLE. Clinical efficacy outcomes analyzed through month 42 included time to event for all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH), ACM alone, first CVH alone, ACM or recurrent CVH, change from baseline in NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, serum transthyretin, and Kansas City Cardiomyopathy Questionnaire Overall Summary score. Safety outcomes were analyzed through month 42.

RESULTS::

Overall, 438 of 632 participants in ATTRibute-CM completed treatment, and 389 enrolled in the ongoing OLE (263 continuous acoramidis and 126 placebo to acoramidis). The hazard ratio for ACM or first CVH was 0.57 (95% CI, 0.46–0.72) at month 42 based on a stratified Cox proportional hazards model ( P <0.0001) favoring continuous acoramidis. Similar analyses were performed on ACM alone and first CVH alone, with hazard ratios of 0.64 (95% CI, 0.47–0.88) and 0.53 (95% CI, 0.41–0.69), respectively, at month 42. Treatment effects for NT-proBNP and 6-minute walk distance also favored continuous acoramidis. On initiation of open-label acoramidis in the placebo-to-acoramidis arm, there was a prompt increase in serum transthyretin. Quality of life assessed by Kansas City Cardiomyopathy Questionnaire Overall Summary score was well preserved in continuous-acoramidis participants compared with the placebo-to-acoramidis participants. No new clinically important safety issues were identified in this long-term evaluation.

CONCLUSIONS::

Early initiation and continuous use of acoramidis in the ATTRibute-CM study through month 42 of the ongoing OLE study were associated with sustained clinical benefits in a contemporary transthyretin amyloid cardiomyopathy cohort, with no clinically important safety issues newly identified.

REGISTRATION::

URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04988386.

01 Mar 2025·CURRENT OPINION IN CARDIOLOGY

New therapies to treat cardiac amyloidosis

Review

Author: Kamna, Daniel ; Nguyen, Olives ; Masri, Ahmad

Purpose of review:

Review advancements in therapies for transthyretin (ATTR-CM) and immunoglobulin light chain (AL-CM) cardiac amyloidosis.

Recent findings:

In ATTR-CM, tafamidis remains the cornerstone therapy, with Food and Drug Administration (FDA) approval for over 5 years. Acoramidis, another transthyretin stabilizer, has very recently been FDA-approved following positive results in the ATTRibute-CM trial. Vutrisiran, a transthyretin gene silencer, demonstrated efficacy in the HELIOS-B trial and awaits FDA review. Eplontersen's CARDIO-TTRansform trial, the largest ATTR-CM study to date, is expected to report by late 2025. Innovative approaches such as NTLA-2001 (a CRISPR-Cas9 therapy) and fibril depleters like ALXN2220 and coramitug are advancing in clinical trials. In AL-CM, daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) has established itself as the standard of care. Novel antiplasma cell therapies include CAR-T cells and bispecific antibodies (teclistimab) and fibril depleters. Birtamimab improved survival in advanced AL-CM during the VITAL trial and is under investigation in AFFIRM-AL. Anselamimab is in phase III CARES trials, whereas AT-02 undergoes early-phase testing for ATTR-CM and AL-CM.

Summary:

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.

01 Mar 2025·JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Efficacy of Acoramidis on All-Cause Mortality and Cardiovascular Hospitalization in Transthyretin Amyloid Cardiomyopathy

Article

Author: Garcia-Pavia, Pablo ; Katz, Leonid ; Obici, Laura ; Gibbs, Simon D J ; Grogan, Martha ; Mahaffey, Kenneth W ; Judge, Daniel P ; Soman, Prem ; Lystig, Ted ; Alexander, Kevin M ; Castaño, Adam ; Siddhanti, Suresh ; Tamby, Jean-François ; Cao, Xiaofan ; Masri, Ahmad ; Fox, Jonathan C ; Fontana, Marianna ; Gillmore, Julian D ; Cappelli, Francesco ; Hanna, Mazen ; Maurer, Mathew S

BACKGROUND:

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed chronic disease associated with progressive heart failure that results in impaired quality of life, repeated hospitalizations, and premature death. Acoramidis is a selective, oral transthyretin stabilizer recently approved by the U.S. Food and Drug Administration for the treatment of ATTR-CM. In a phase 3, randomized, double-blind study (ATTRibute-CM [Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy]), acoramidis was well tolerated and showed clinical efficacy in improving the primary endpoint, a hierarchical combination of all-cause mortality (ACM), cardiovascular-related hospitalization (CVH), N-terminal pro-B-type natriuretic peptide level, and 6-minute walk distance.

OBJECTIVES:

The goal of this study was to characterize the efficacy of acoramidis on ACM and CVH.

METHODS:

In ATTRibute-CM, participants with ATTR-CM were randomized 2:1 to receive acoramidis hydrochloride (800 mg twice daily) or placebo for 30 months. Efficacy analyses were conducted in the modified intention-to-treat population (participants with a baseline estimated glomerular filtration rate ≥30 mL/min/1.73 m²). CVH and the composite of ACM or first CVH were plotted by using Kaplan-Meier curves and summarized with a stratified Cox proportional hazards model. The annualized frequency of CVH was analyzed by using a negative binomial regression model. Subgroup analyses were conducted for the composite of ACM or first CVH.

RESULTS:

Of the 632 participants randomized to treatment, 611 (97%) were included in efficacy analyses (acoramidis, n = 409; placebo, n = 202). Compared with placebo, acoramidis reduced the occurrence of the composite of ACM or first CVH (acoramidis, 35.9%; placebo, 50.5%; HR: 0.64; 95% CI: 0.50-0.83; P = 0.0008) and of first CVH (acoramidis, 26.7%; placebo, 42.6%; HR: 0.60; 95% CI: 0.45-0.80; P = 0.0005), with Kaplan-Meier curves separating at month 3 and continuing to diverge through month 30. Annualized frequency of CVH was reduced with acoramidis compared with placebo (acoramidis, 0.22; placebo, 0.45; relative risk ratio: 50%; 95% CI: 0.36-0.70; P < 0.0001). The efficacy of acoramidis on the composite of ACM or first CVH was consistent across subgroups. Acoramidis was well tolerated, with no safety signals of potential clinical concern identified.

CONCLUSIONS:

In participants with ATTR-CM, acoramidis reduced the composite of ACM or first CVH vs placebo, with an early effect driven by a reduction in CVH. (Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy [ATTRibute-CM]; NCT03860935).

154

News (Medical) associated with Acoramidis

31 Mar 2025

·www.globenewswire.com

Acoramidis Shows Statistically Significant Improvements in Cardiovascular Outcomes in Patients with Variant ATTR-CM

Acoramidis’s hazard ratio of .41 for time to ACM or first CVH versus placebo in the ATTRibute-CM study subgroup of ATTRv-CM patients achieved statistical significance in a pre-specified analysisThis profound treatment effect, due to the near-complete stabilization (≥90%) and binding of TTR, represents the greatest observed benefit to date for ATTRv-CM patients, an ATTR-CM population with poor prognosis In the ATTRibute-CM study, acoramidis demonstrated the most rapid benefit seen in any Phase 3 study of ATTR-CM to date in both ATTRv-CM and ATTRw-CM patients: In as few as 3 months, the time to first event (ACM or CVH) durably separated relative to placeboA 42% reduction in composite ACM and recurrent CVH events relative to placebo at Month 30A 50% reduction in the cumulative frequency of CVH events relative to placebo at Month 30 Acoramidis is approved as Attruby™ by the U.S. FDA and is approved as BEYONTTRA™ by the European Commission and Japanese Pharmaceuticals and Medical Devices Agency PALO ALTO, Calif., March 31, 2025 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a new type of biopharmaceutical company focused on genetic diseases, today presented results showing statistically significant improvements in clinical outcomes as compared to placebo for time to all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) in both variant (ATTRv) and wild-type (ATTRwt) transthyretin amyloid cardiomyopathy (ATTR-CM) patients from a pre-specified subgroup analysis of ATTRibute-CM, its Phase 3 trial of acoramidis in ATTR-CM. These data were presented at the American College of Cardiology (ACC) Annual Scientific Sessions & Expo in a poster presentation by Margot Davis, M.D. of Vancouver General Hospital, Canada. Acoramidis is a selective small molecule, orally administered, near-complete (≥90%) transthyretin (TTR) stabilizer. “Variant ATTR-CM patients’ condition often presents at an earlier age and progresses more rapidly than patients with wild-type disease, which translates into a worse prognosis in many such patients. We know that pathogenic TTR variant tetramers are less stable than the wild-type tetramer and this property is directly responsible for the more aggressive disease trajectory for these patients. The findings from the ATTRibute-CM trial clearly demonstrate that the rapid and sustained increases in serum TTR levels upon initiation of acoramidis treatment in variant ATTR-CM patients were similar if not greater than those observed in wild-type ATTR-CM patients,” said Jonathan Fox, M.D., Ph.D., president and chief medical officer of BridgeBio Cardiorenal. “This provides evidence that acoramidis is the only disease-modifying therapy that provides near-complete stabilization of TTR, improving clinical outcomes in both variant and wild-type ATTR-CM patients to an extent that is independently statistically significant in both subgroups.” “Given the significant unmet need for patients with ATTRv-CM, we are highly encouraged by the magnitude of efficacy seen with acoramidis. A pre-specified analysis in the ATTRv-CM population has shown a statistically significant 59% hazard reduction for the composite of ACM and CVH at Month 30, demonstrating that acoramidis can make a profound impact on patients’ lives,” said Kevin Alexander, M.D. of Stanford University School of Medicine. Relative increases in serum TTR concentrations resulting from greater TTR stability have been associated with reduced risk of all-cause and cardiovascular mortality in the general population in recent literature.1 The serum TTR level increase with acoramidis was accompanied by a significant reduction in the risk of ACM or first CVH versus placebo in both the ATTRv-CM (59.1% risk reduction, .41 hazard ratio) and ATTRwt-CM (31.2% risk reduction, .69 hazard ratio) subgroups. Acoramidis treatment also led to a greater proportional increase in serum TTR in ATTRv-CM patients and achieved similar absolute serum TTR levels in both ATTRv- and ATTRwt-CM patients, which is an in vivo reflection of acoramidis’ near-complete (≥90%) TTR stabilization. Additional acoramidis poster presentations and moderated posters at the ACC Annual Scientific Sessions & Expo included: Acoramidis Improves NYHA Class at Month 30 Versus Placebo in Patients with ATTR-CM: Results from the ATTRibute-CM Study shared by Kevin Alexander, M.D. of Stanford University School of Medicine In the ATTRibute-CM study, acoramidis treatment resulted in a greater proportion of patients whose New York Heart Association (NYHA) Class was stable or improved at Month 30 vs placebo, indicating better stabilization in their heart failure symptoms and functional status. The NYHA classification system categorizes heart failure patients into four classes based on a clinical assessment of their physical activity limitations and associated symptoms due to their condition In Participants Treated with Acoramidis, Addition of Concomitant Tafamidis Did Not Further Increase Serum TTR Levels shared by Mathew Maurer, M.D. of Columbia University Irving Medical Center The poster showed that in patients with ATTR-CM, treatment with acoramidis significantly increased serum TTR levels whether compared to placebo alone or in those who received placebo as well as tafamidis. Conversely, the addition of tafamidis to acoramidis did not demonstrate any further increase in serum TTR levels, reflecting the lack of any additional stabilization benefit of serum TTR from tafamidis in vivo, as previously demonstrated in vitro. The safety profile in this limited dataset of concomitant acoramidis and tafamidis was similar to the overall safety profile of acoramidis alone Primary Endpoint Efficacy Results in the ATTRibute-CM Study: Pre-specified Sensitivity Analyses Addressed Tafamidis Use shared by Daniel P. Judge, M.D. of Medical University of South Carolina Pre-specified analyses showed consistent results with the primary analysis, demonstrating that the concomitant use of tafamidis did not alter the statistical significance of the primary efficacy endpoint Acoramidis-mediated Early Increase in Serum Transthyretin Level Reduces Cardiovascular-related Hospitalizations and Mortality: Insights from the ATTRibute-CM Study shared by Nitasha Sarswat, M.D. of UChicago Medicine In this post-hoc analysis of ATTRibute-CM, incremental increases in serum TTR levels on Day 28, achieved with acoramidis, may independently predict greater reduction in risks of cardiovascular mortality and of first CVH in patients with ATTR-CM Robustness of Primary Endpoint Efficacy Results with Acoramidis in ATTR-CM in the ATTRibute-CM Study: Pre-specified NT-proBNP Sensitivity Analyses shared by Jan Griffin, M.D. of Medical University of South Carolina This poster shows that pre-specified sensitivity analyses using higher N-terminal pro-type natriuretic peptide (NT-proBNP) thresholds for declaring a difference in the changes in NT-proBNP levels between the treatment arms showed consistent efficacy favoring acoramidis in patients with ATTR-CM. This confirms the robustness of the acoramidis treatment effect regardless of NT-proBNP progression thresholds Geographic Healthcare Disparities and Diagnostic Trends Among Patients with Transthyretin Amyloid Cardiomyopathy shared by Joshua Mitchell, M.D. of Washington University School of Medicine in St. Louis Findings presented show that the diagnosed prevalence of amyloid has significantly increased since 2017 in the setting of available treatment, improved awareness and less invasive diagnostics. However, there remain geographic disparities and racial differences in ATTR-CM prevalence Acoramidis is approved as Attruby by the U.S. FDA and is approved as BEYONTTRA by the European Commission and Japanese Pharmaceuticals and Medical Devices Agency with all labels specifying near-complete stabilization of TTR. More data on the benefit of Attruby for ATTRv-CM patients is planned for future medical meetings. 1Christoffersen M et al. Transthyretin Tetramer Destabilization and Increased Mortality in the General Population. JAMA Cardiol. 2024 Dec 4:e244102. About Attruby™ (acoramidis)Attruby is the first near-complete (≥90%) stabilizer of Transthyretin (TTR) approved in the U.S. for the treatment of the cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular death and cardiovascular-related hospitalization. Attruby was generally well-tolerated. The most common side effects were mild and included diarrhea and abdominal pain that were resolved without drug discontinuation. BridgeBio offers an extensive suite of programs to help patients access our medicines. About BridgeBioBridgeBio Pharma (BridgeBio; NASDAQ:BBIO) is a new type of biopharmaceutical company founded to discover, create, test, and deliver transformative medicines to treat patients who suffer from genetic diseases. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn, Twitter and Facebook. BridgeBio Forward-Looking StatementsThis press release contains forward-looking statements. Statements in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act), which are usually identified by the use of words such as “anticipates,” “believes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “seeks,” “should,” “continue,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act. These forward-looking statements, including statements relating to the clinical and therapeutic potential of our programs and product candidates, including our clinical development program for acoramidis for patients with transthyretin amyloid cardiomyopathy and the statements regarding the potential clinical benefits or of potential benefits for ATTR-CM patients in the quotes of Dr. Alexander, reflect our current views about our plans, intentions, expectations and strategies, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, and strategies as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations, or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, initial and ongoing data from our preclinical studies and clinical trials not being indicative of final data, the potential size of the target patient populations our product candidates are designed to treat not being as large as anticipated, the design and success of ongoing and planned clinical trials, future regulatory filings, approvals and/or sales, despite having ongoing and future interactions with the FDA and other regulatory agencies to discuss potential paths to registration for our product candidates, the FDA or such other regulatory agencies not agreeing with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, the continuing success of our collaborations, our ability to obtain additional funding, including through less dilutive sources of capital than equity financings, potential volatility in our share price, the impacts of current macroeconomic and geopolitical events, including changing conditions from, hostilities in Ukraine, and in Israel and the Gaza Strip, increasing rates of inflation and changing interest rates, on business operations and expectations, as well as those risks set forth in the Risk Factors section of our most recent Annual Report on Form 10-K and our other filings with the U.S. Securities and Exchange Commission. Moreover, we operate in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of our management as of the date of this press release, and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. BridgeBio Media Contact:Bubba Murarka, EVP Communicationscontact@bridgebio.com (650)-789-8220

Clinical ResultDrug ApprovalPhase 3AHA

27 Mar 2025

·www.globenewswire.com

Beyonttra™ (acoramidis), the First Near-complete TTR Stabilizer (≥90%), Approved in Japan to Treat ATTR-CM

In the Japanese Phase 3 study, 0% mortality was reported over the 30-month treatment period and acoramidis was well-tolerated The approval was based on a Japanese Phase 3 study and the global ATTRibute-CM Phase 3 trial, which demonstrated the most rapid benefit seen in any Phase 3 study of ATTR-CM to date. Key data from the ATTRibute-CM study include: In as few as 3 months, the time to first event (all-cause mortality (ACM) or cardiovascular-related hospitalization (CVH)) durably separated relative to placeboA 42% reduction in composite ACM and recurrent CVH events relative to placebo at Month 30A 50% reduction in the cumulative frequency of CVH events relative to placebo at Month 30 BridgeBio will receive a $30 million milestone payment from Alexion, AstraZeneca Rare Disease, with royalties in the low double digits on net sales of Beyonttra in Japan PALO ALTO, Calif., March 27, 2025 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a new type of biopharmaceutical company focused on genetic diseases, today announced the Japanese Ministry of Health, Labour and Welfare has approved acoramidis, under the brand name Beyonttra, for the treatment of adults with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). Acoramidis is a selective small molecule, orally administered, near-complete (≥90%) transthyretin (TTR) stabilizer. Relative increases in serum TTR concentrations resulting from greater TTR stability have been associated with reduced risk of all-cause and cardiovascular mortality in the general population in recent literature.1 ATTR-CM is a progressive, fatal disease that presents as an infiltrative, restrictive cardiomyopathy resulting in heart failure. Alexion, AstraZeneca Rare Disease will be responsible for all commercial activity for Beyonttra in Japan. “There is significant need for new treatment options for ATTR-CM, a progressive, fatal disease, worldwide. This latest approval marks an important development for the ATTR-CM community, and we are pleased that patients living with this condition in Japan now have a new treatment option that offers early and sustained reductions in cardiovascular events,” said Dr. Jonathan Fox, BridgeBio Cardiorenal Chief Medical Officer. The approval in Japan is based on positive results from a Phase 3 open-label, single-arm study conducted in Japan by Alexion, AstraZeneca Rare Disease, and the positive results from the global ATTRibute-CM Phase 3 study. In the Japanese trial, acoramidis was generally well tolerated and 0% mortality was reported during the 30-month acoramidis treatment period. BridgeBio’s global ATTRibute-CM Phase 3 trial showed early separation at 3 months in time to first event (ACM or CVH) durably separated relative to placebo. Furthermore, within the global ATTRibute-CM trial acoramidis led to a 42% reduction in composite ACM and recurrent CVH events relative to placebo at Month 30, as well as a 50% reduction in the cumulative frequency of CVH events relative to placebo at Month 30. Alexion, AstraZeneca Rare Disease, maintains an exclusive license with BridgeBio’s affiliate, Eidos Therapeutics, Inc. to develop and commercialize acoramidis in Japan. Based on the terms of the agreement, BridgeBio will receive a $30 million milestone payment upon approval in Japan, as well as royalties in the low double digits on sales of acoramidis in Japan, with commercialization efforts planned in the first half of 2025. 1Christoffersen M et al. Transthyretin Tetramer Destabilization and Increased Mortality in the General Population. JAMA Cardiol. 2024 Dec 4:e244102. Beyonttra (acoramidis) Beyonttra is an orally administered near-complete (≥90%) stabilizer of transthyretin (TTR) indicated for the treatment of wild-type or variant transthyretin amyloid cardiomyopathy (ATTR-CM) in adults. Beyonttra was generally well-tolerated. Please refer the Japanese Prescribing Information as made available by the PMDA for Japanese specific safety labelling. In the US prescribing information, where acoramidis is approved under the brand name Attruby™, the most common side effects were mild and included diarrhea and abdominal pain that were resolved without drug discontinuation. Alexion maintains an exclusive license with BridgeBio’s affiliate, Eidos Therapeutics, Inc., to develop and commercialize Beyonttra in Japan. About BridgeBio Pharma, Inc.BridgeBio Pharma, Inc. (BridgeBio) is a new type of biopharmaceutical company founded to discover, create, test, and deliver transformative medicines to treat patients who suffer from genetic diseases. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn, Twitter and Facebook. BridgeBio Pharma, Inc. Forward-Looking StatementsThis press release contains forward-looking statements. Statements in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act), which are usually identified by the use of words such as “anticipates,” “believes,” “continues,” “estimates,” “expects,” “hopes,” “intends,” “may,” “plans,” “projects,” “remains,” “seeks,” “should,” “will,” and variations of such words or similar expressions. BridgeBio intends these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act. These forward-looking statements, including statements relating to the impact of Beyonttra on clinical outcomes; and the potential benefits of Beyonttra, including its efficacy and potential to reduce ACM or CVH events, reflect BridgeBio’s current views about its plans, intentions, expectations, and strategies, which are based on the information currently available to BridgeBio and on assumptions BridgeBio has made. Although BridgeBio believes that its plans, intentions, expectations, and strategies, as reflected in or suggested by these forward-looking statements, are reasonable, BridgeBio can give no assurance that the plans, intentions, expectations, or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties, and assumptions, including, but not limited to, the risks associated with BridgeBio’s dependence on third parties for development, manufacture, and commercialization activities related to Beyonttra; government and third-party payor actions; risks and uncertainties relating to competitive products and other changes that may limit demand for Beyonttra; the risk that regulatory authorities may require additional studies or data to support the continued commercialization of Beyonttra; the risk that drug-related adverse events may be observed during commercialization or clinical development; the risk that data and results may not meet regulatory requirements or otherwise be sufficient for further development, regulatory review, or approval; the risk of other regulatory agencies not agreeing with BridgeBio’s regulatory approval strategies, components of BridgeBio’s filings (such as clinical trial designs, conduct, and methodologies), or the sufficiency of data submitted; the continuing success of its collaborations, including compliance with applicable regulations for the purchase, distribution, storage, export, and sale of active pharmaceutical ingredients and medicinal products; uncertainty regarding any impacts due to global health emergencies, including delays in regulatory review, manufacturing, and supply chain interruptions; adverse effects on healthcare systems and disruption of the global economy; the impacts of current macroeconomic and geopolitical events, including changing conditions from hostilities in Ukraine and in Israel and the Gaza Strip; and increasing rates of inflation and changing interest rates on BridgeBio’s business operations and expectations. These risks, as well as those set forth in the Risk Factors section of BridgeBio’s most recent Annual Report on Form 10-K and its other filings with the U.S. Securities and Exchange Commission, should be carefully considered. Moreover, BridgeBio operates in a highly competitive and rapidly changing environment, in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of BridgeBio’s management as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, BridgeBio assumes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events, or otherwise. BridgeBio Media Contact:Bubba Murarka, EVP Communicationscontact@bridgebio.com (650)-789-8220

Phase 3License out/inClinical ResultDrug Approval

21 Mar 2025

·endpts.com

Alnylam hopes its broad ATTR-CM label can give Amvuttra an edge in heart disease

Alnylam will likely face challenges in turning a profit this year, despite executives promising to do so. But the label for its newly-approved Amvuttra indication may give it an advantage over its rivals Pfizer and BridgeBio. That’s because Amvuttra’s label for transthyretin amyloid cardiomyopathy, or ATTR-CM, is broader than its competitors, saying it reduces the likelihood of hospitalization, death and urgent heart failure visits. Pfizer’s Vyndaqel/Vyndamax franchise, approved in 2019, and BridgeBio’s recently-approved Attruby are only indicated to reduce hospitalization and death. “The inclusion of urgent heart failure visits is unique and recognizes the effects that we’re also seeing on this important consequence of ATTR-cardiomyopathy,” Alnylam chief medical officer Pushkal Garg said on an investor call Thursday evening. Garg touted the broader label as key to getting Amvuttra in as many first-line patients as possible. Wall Street appeared to like what it saw as well after the FDA approved the drug for the rare heart disease. After a trading halt Thursday afternoon, Alnylam’s stock $ALNY was up more than 10% in Friday’s session. Most analysts expect getting Amvuttra into first-line patients will determine whether Alnylam is profitable this year, and they don’t think it will be easy. Both Vyndaqel/Vyndamax and Attruby are oral stabilizers, a class that’s been on the market for several years that works by stabilizing the TTR protein and preventing misfolding. Amvuttra, meanwhile, is the first therapy approved in its class for ATTR-CM, reducing the expression of the TTR gene through RNA interference. There’s also a wrinkle when it comes to second-line patients who could switch from the Pfizer and BridgeBio drugs to Amvuttra: There is no formal definition for ATTR-CM disease progression. The decisions that patients and their doctors make about which therapy to take — one of the Pfizer/BridgeBio stabilizers, Alnylam’s silencer or both mechanisms in combination — will be made on a case-by-case basis. In an interview before Thursday’s approval, CEO Yvonne Greenstreet told Endpoints News the company can support a successful launch in ATTR-CM by leveraging its existing physician network for doctors who prescribe Amvuttra in its other indication, hereditary transthyretin-mediated amyloidosis (hATTR) with polyneuropathy. She also said she believes Alnylam’s clinical trial data will make patients’ choices easier, regardless of whether they’ve taken a stabilizer before. “The simpler it is for physicians, the easier it is for them to come to a determination,” Greenstreet told Endpoints. “But I have to say that, even without specific, clear guidelines with, let’s say, one biomarker to assess, physicians are able to interpret whether their patients are progressing or not.” The company is forecasting revenues between $1.6 billion and $1.725 billion for its ATTR medicines (Amvuttra and Onpattro) this year after they made about $1.2 billion in 2024, giving them what Greenstreet has called a “path to profitability.” Alnylam lost $278 million last year. Alnylam is maintaining the same price of about $476,000 per year for Amvuttra in ATTR-CM as it had for hATTR. It’s nearly double what Pfizer and BridgeBio charge for their drugs, at around $250,000 and $244,500, respectively. Despite that, analysts largely saw the label as a win for Alnylam in notes out to investors Thursday evening and Friday morning. TD Cowen’s Ritu Baral wrote the inclusion of urgent heart failure visits will help in payer talks, “especially for front line use,” as ATTR-CM care has moved into the outpatient setting. With the pricing information confirmed, Baral estimates $254 million in ATTR-CM sales and peak sales of $2.3 billion by 2030. Stifel analyst Paul Matteis, meanwhile, wrote that he believes investor fixation on label language was overblown, questioning whether it would have an impact on patient uptake. But the fact that Alnylam was able to deliver on a differentiated label is still a success. “How much this will matter remains open for debate, but on the margin it could help with the marketing message and it also may be helpful with [Alnylam’s] ability to maintain premium pricing,” Matteis wrote. That high price may make some payers balk in insurance discussions, Leerink analyst Mani Foroohar noted. Most of the patient population is covered under Medicare Part B, however, giving doctors different prescribing incentives. Greenstreet said that about 70% of patients taking Amvuttra for hATTR pay no out-of-pocket costs, and she expects Alnylam to eventually get to about that level in ATTR-CM as well. That dynamic, when combined with the data and label, are all the pieces Alnylam needs to put together.

Drug Approval

100 Deals associated with Acoramidis

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KEGG	Wiki	ATC	Drug Bank
D11972	-	-	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Amyloidosis, Hereditary, Transthyretin-Related	European Union	BridgeBio Pharma, Inc.	10 Feb 2025
Amyloidosis, Hereditary, Transthyretin-Related	Iceland	BridgeBio Pharma, Inc.	10 Feb 2025
Amyloidosis, Hereditary, Transthyretin-Related	Liechtenstein	BridgeBio Pharma, Inc.	10 Feb 2025
Amyloidosis, Hereditary, Transthyretin-Related	Norway	BridgeBio Pharma, Inc.	10 Feb 2025
Transthyretin Amyloid Cardiomyopathy	United States	BridgeBio Pharma, Inc.	22 Nov 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Polyneuropathies	Phase 3	United States	Eidos Therapeutics, Inc.	01 Apr 2025
Polyneuropathies	Phase 3	Bulgaria	Eidos Therapeutics, Inc.	01 Apr 2025
Polyneuropathies	Phase 3	Italy	Eidos Therapeutics, Inc.	01 Apr 2025
Polyneuropathies	Phase 3	Spain	Eidos Therapeutics, Inc.	01 Apr 2025
Transthyretin-related (ATTR) familial amyloid polyneuropathy	Phase 3	United States	Eidos Therapeutics, Inc.	21 Oct 2020
Senile cardiac amyloidosis	Phase 2	United States	Eidos Therapeutics, Inc.	27 Apr 2018
Amyloidosis	Phase 1	United Kingdom	Eidos Therapeutics, Inc.	28 Mar 2021

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03860935 (ATTRibute-CM, Pubmed \| J Am Coll Cardiol)	Phase 3	Amyloidosis, Hereditary, Transthyretin-Related \| Transthyretin Amyloid Cardiomyopathy N-terminal pro-B-type natriuretic peptide level	632	Acoramidis hydrochloride 800 mg twice daily	zrhqdzyjmj(ayzajhbdsd): relative risk ratio = 50 (95% CI, 0.36 - 0.7), P-Value = < 0.0001 View more	Positive	01 Mar 2025
				Placebo
NCT04622046 (CTgov)	Phase 3	Transthyretin Amyloid Cardiomyopathy	25	ALXN2060	zkbpzlasxa(dajbgkzxmz) = lrvvxseosb hmgitlbgki (asvcqrtyts, 9.182) View more	-	16 Dec 2024
NCT03860935 (FDA_CDER) Manual	Phase 3	Transthyretin Amyloid Cardiomyopathy	611	ATTRUBY 712 mg	vkzyuqkvpc(weyvgmsvid): P-Value = 0.018 View more	Positive	22 Nov 2024
				Placebo
NCT03860935 (ATTRibute-CM, Company_Website) Manual	Phase 3	Transthyretin Amyloid Cardiomyopathy	389	Acoramidis	rjhyllnahf(bnfzcsupkk) = unvimkbzvu smolbaanba (jeutcxpdpr ) View more	Positive	18 Nov 2024
				Placebo	-
NCT03860935 (ATTRibute-CM, GlobeNewswire \| PipelineReview) Manual	Phase 3	Transthyretin Amyloid Cardiomyopathy	-	Acoramidis	lygohghncv(vywffpafnl) = ulwniqfoli rqnmivezpp (kaioaghqqy )	Positive	27 Sep 2024
				Placebo	-
NCT03860935 (ATTRibute-CM, ESC2024)	Phase 3	Transthyretin Amyloid Cardiomyopathy serum TTR levels	611	Acoramidis	qceemmdqgw(ppokbjndvz) = hjjlmnimny wftvmhxruz (eahumxutku )	Positive	30 Aug 2024
				Tafamidis	qceemmdqgw(ppokbjndvz) = jynkcjbbdi wftvmhxruz (eahumxutku, 0.4 (4.92))
NCT03860935 (ATTRibute-CM, CTgov)	Phase 3	Amyloidosis, Hereditary, Transthyretin-Related \| Transthyretin Amyloid Cardiomyopathy	632	acoramidis (Acoramidis HCl 800 mg)	hgfxkecpgb = wnmbqcwgee dhfdaczvnh (qptzewkyks, tiesvanewn - fbopgblfyj) View more	-	27 Jun 2024
				Placebo Oral Tablet (Placebo)	hgfxkecpgb = jgjiwknqnk dhfdaczvnh (qptzewkyks, mvykbdomph - qefdbccvnj) View more
NCT03860935 (ATTRibute-CM, Company_Website) Manual	Phase 3	Transthyretin Amyloid Cardiomyopathy	-	Acoramidis	ejdmdbhocf(isuorvtujx) = every 5mg/dL increase in serum TTR level at day 28 after treatment initiation, the risk of death through Month 30 was reduced by 30.9% (by the logistic model) and 26.1% (by the Cox proportional hazards model) thsikiqpjw (ujzarkegbs ) View more	Positive	29 May 2024
				Placebo
ESC2024	Not Applicable	Transthyretin Amyloid Cardiomyopathy	-	Acoramidis	zzvbqklxmi(ghqjrmgrhq) = gnmbriljxx jgcxsqeflr (ocyqvtdnsd, 0.07 - 0.18)	-	13 May 2024
ESC2024	Not Applicable	Transthyretin Amyloid Cardiomyopathy	-	Acoramidis	llccmlbids(ctwggrdwla) = A statistically significant (p<0.0001) and clinically meaningful treatment benefit on KCCQ-OS was observed with acoramidis versus placebo gohuyttwul (erwxqdfpir ) View more	-	13 May 2024
				Placebo

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