Tafamidis

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

关注并星标CPHI制药在线近日，专注于RNAi（RNA干扰）疗法的Alnylam公司宣布，旗下siRNA（小干扰RNA）疗法Amvuttra（vutrisiran）获FDA批准，成功拓展适应症，用于治疗转甲状腺素蛋白淀粉样变性（ATTR-CM）成人患者，成为首 款治疗ATTR-CM的siRNA疗法。之前，针对ATTR-CM的获批药物已有两款，那么，作为后来者，vutrisiran能顺利突围吗？罕见病赛道红利转甲状腺素蛋白淀粉样变性心肌病（ATTR-CM）是一种破坏性强、进展迅速且最终致命的疾病。从病理上讲，ATTR-CM患者由于衰老或基因突变，导致主要负责转运甲状腺素和视黄醇结合蛋白-维生素A复合物的转甲状腺素蛋白（TTR）四聚体解离，形成不稳定的单体，之后错误折叠，并作为淀粉样纤维在心肌间质沉积，从而使心肌变得僵硬，最终导致心力衰竭。人类ATTR基因存在于18号染色体上。根据TTR基因的序列，ATTR-CM可分为wtATTR-CM（野生型）或hATTR-CM（突变型）。与wtATTR-CM患者相比，hATTR-CM患者的临床病程变化更大，严重程度更高。据估计，ATTR-CM发病率不到1%，已于2018年被收录于《中国第一批罕见病目录》中。但由于缺乏早期诊断的方法，其发病率可能被错误低估。根据一项法国的全国范围流行病学数据，2011年至2017年间，法国ATTR-CM患者发病率涨幅超6倍，从2011年的0.6/100000人每年增至2017年的3.6/100000人每年。在中国，由于ATTR-CM临床表现多样，导致对该病认识和重视不足，极易漏诊误诊，中国ATTR-CM的诊断率甚至不足1%。另外据统计，全球约有80%的ATTR-CM患者并没有得到治疗，约有75%的患者对目前的标准治疗没有应答或者仅有部分应答。因此，ATTR-CM治疗领域存在巨大的未竟需求。vutrisiran获批，三雄争霸局面形成由于ATTR-CM的病理机制是由TTR解离和错误折叠导致，因此针对这种疾病治疗药物的开发主要分为稳定TTR解离和抑制TTR合成两种思路。2019年5月，辉瑞的复方制剂Vyndaqel（氯苯唑酸葡甲胺，tafamidis meglumine）+Vyndamax（氯苯唑酸）获FDA批准上市，这是TTR稳定剂氯苯唑酸的2种口服制剂，能够选择性地与TTR结合，稳定其四聚体结构。Vyndaqel的III期研究以30个月时的全因死亡率、心血管相关住院频率为主要终点。结果显示，与安慰剂相比，试验组的全因死亡率和心血管相关住院频率分别相对降低了30% 和 32% 。与安慰剂组相比，试验组关键次要终点6MWD（6分钟步行距离测试）、KCCQ-OS（堪萨斯城心肌病问卷总体概要评分）有明显改善。之后Vyndaqel相继在欧盟、中国等获批。据辉瑞财报，2021-2023年Vyndaqel全球销售额分别为20.15、24.47、33.21亿美元。2024年11月，全球第二款TTR稳定剂获FDA批准上市，BridgeBio Pharma（以下简称BridgeBio）宣布FDA批准了其ATTR-CM新药——Attruby（acoramidis）上市。据该药ATTRibute-CM研究结果显示，试验达到所有主要终点，试验组4个主要终点（治疗30个月时的全因死亡率、心血管事件累积发生频率、相较于基线时NT-proBNP——一种心力衰竭相关生物标志物及6MWD的改善情况）结果均优于安慰剂组。30个月的治疗期间，相比于安慰剂组，试验组的全因死亡率和心血管相关住院相关风险降低了42%。相比于安慰剂组，心血管事件累积发生频率降低了50%。Attruby的上市，势必对Vyndaqel的市场份额造成挤压。BridgeBio曾表示，Attruby是第一个，也是唯一一个在标签中正式注明能几乎/完全稳定TTR的药物。公司预期该药2028年销售额可达10亿美元。面对上述两款强敌药物，本次获批的Amvuttra能成功突围吗？强敌环绕，Vutrisiran胜算几何？Vutrisiran是一款siRNA疗法，其使用Alnylam公司的增强稳定性化学（ESC）-GalNAc结合物递送平台，具有更高的效力和高代谢稳定性。与前两种药物不同，Vutrisiran通过直接靶向沉默TTR基因的mRNA，从源头上减少TTR蛋白的生成，阻断淀粉样纤维的形成。2022年6月，Vutrisiran首次获FDA批准上市，用于治疗成人ATTR淀粉样变性多发性神经病变（ATTR-PN）。本次适应症拓展获FDA批准，主要基于一项III期HELIOS-B研究。研究的主要终点是第36个月全人群的全因死亡和复发心血管（CV）事件的复合发生率。结果显示，在双盲期间，总人群的全因死亡和复发CV事件的复合发生率显著降低（HR=0.718，p=0.0118）；单药治疗人群（基线时未接受氯苯唑酸治疗）的全因死亡和复发CV事件的复合发生率亦显著降低（HR=0.672，p=0.0162）。除了能从根源治疗疾病外，Vutrisiran每年仅需4次皮下注射，而Bridgebio的Attruby则需每日口服两次，辉瑞的Vyndaqel需每日一次。Vutrisiran可大大提高患者依从性。价格方面，虽然Vutrisira每年需要47.6万美元，远远超过Vyndaqel的25万美元和Attruby的24.4万美元。但在适应症ATTR-PN领域，Vutrisiran的保险覆盖率约为99%的患者，其中大多数患者无需支付任何自付费用，预计在ATTR-CM中也将实现类似的支付方式。基于以上因素，Vutrisiran很可能在商业化中实现后来居上。目前，已获批的ATTR-CM治疗方案已包括TTR蛋白稳定剂和小核酸药物。除此之外，Intellia Therapeutics的基因编辑药物NTLA-2001在针对ATTR-CM治疗中，已初露头角。该药通过LNP向患者肝脏细胞递送CRISPR/Cas9基因编辑系统，靶向敲除TTR基因，抑制TTR蛋白表达，目前已进入临床III期研究，基于I期优秀数据，值得期待。主要参考资料：       1.Alnylam announces FDA approval of vutrisiran, the first RNAi therapeutic to reduce cardiovascular death.2.Gillmore Julian D,Judge Daniel P,Cappelli Francesco et al. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy.[J] .N Engl J Med, 2024, 390: 132-142.3.BridgeBio Pharma Presents Additional Clinical Outcomes Data from the Phase 3 ATTRibute-CM Study of Acoramidis in Patients with Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM). globenewswire. November 12, 2023.END2025金笔奖征文活动开启，来投稿吧！领取CPHI & PMEC China 2025展会门票智药研习社课程预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~