Mater Misericordiae & The Children's University Hospitals CLG

近日，全球知名制药企业勃林格殷格翰（Boehringer Ingelheim）宣布，其PDE4抑制剂nerandomilast在治疗特发性肺纤维化（IPF）和进展性肺纤维化（PPF）的两项三期临床试验（FIBRONEER™-IPF和FIBRONEER™-ILD）中均达到了主要终点。然而，尽管试验结果显示出一定的积极意义，但部分华尔街分析师对该药物的“温和”疗效表示失望。在FIBRONEER™-IPF试验中，nerandomilast的两种剂量（9 mg和18 mg）均显著减缓了特发性肺纤维化患者的肺功能下降，与安慰剂相比，患者的用力肺活量（FVC）下降幅度更小。具体而言，在接受nerandomilast治疗的患者中，FVC的平均下降量为114.7 ml，而安慰剂组为183.5 ml。此外，该药物在与现有抗纤维化药物（如Ofev和Esbriet）联合使用时也显示出一定的疗效。复合关键次要终点（首次急性IPF加重的时间、首次因呼吸原因住院或死亡）未达到。在FIBRONEER™-ILD试验中，nerandomilast同样达到了主要终点，在接受nerandomilast治疗的患者中，FVC的平均下降量为98.6 ml，而安慰剂组为165.8 ml。表明其在减缓进展性肺纤维化患者肺功能下降方面具有潜力。Nerandomilast在复合关键次要终点（到首次急性加重的时间，因呼吸系统原因住院或死亡）方面没有统计学意义，但两个治疗组的死亡率都较低：9 mg组（n=33/8.4%）， 18 mg组（n=24/6.1%），与安慰剂组（n=50/12.8%）相比。两项试验的安全性数据与安慰剂组相当，未出现与药物相关的严重不良事件。尽管试验结果积极，但部分分析师对nerandomilast的疗效持谨慎态度。Leerink Partners的分析师在5月19日的一份报告中指出，nerandomilast虽然在一定程度上优于Ofev，但本质上仍是一种“减缓疾病进展”的药物，而非“阻止疾病进展”的药物。他们认为，该药物对肺功能的影响“温和”，不太可能立即改变IPF的治疗格局。此外，nerandomilast与现有药物的联合使用存在一定的复杂性。例如，与Esbriet存在药物相互作用，低剂量的nerandomilast在与Esbriet联合使用时未能改善患者预后。同时，高剂量nerandomilast的腹泻发生率较高（41%），尤其是在与Ofev联合使用时。这些因素可能会限制其在临床中的广泛应用。尽管面临分析师的质疑，勃林格殷格翰对nerandomilast的前景仍持乐观态度。公司表示，nerandomilast的试验结果为IPF和PPF患者带来了新的希望。nerandomilast治疗特发性肺纤维化（IPF）和进行性肺纤维化（PPF）的新药申请已在美国、中国和欧盟提交，其他地区也将跟进中。结束语：勃林格殷格翰的nerandomilast在纤维化肺病的三期试验中取得了积极进展，尽管被华尔街认为疗效“温和”，该药物的成功仍为IPF和PPF患者带来了新的治疗选择，也为未来的肺纤维化研究提供了新的方向。未来，随着更多数据的公布和临床应用的推进，nerandomilast的潜力有望得到更全面的评估。识别微信二维码，可添加药时空小编请注明：姓名+研究方向！

PALO ALTO, CA, USA I February 11, 2025 I BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a new type of biopharmaceutical company focused on genetic diseases, today announced the European Commission has granted marketing authorization in the European Union (EU) for acoramidis, under the brand name BEYONTTRA™, for the treatment of wild-type or variant transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM). Acoramidis is a selective small molecule, orally administered near-complete (≥90%) transthyretin (TTR) stabilizer. ATTR-CM is a progressive fatal disease that presents as an infiltrative, restrictive cardiomyopathy resulting in heart failure. Bayer will be responsible for all commercial activity for acoramidis in the EU. “ATTR-CM is a rapidly progressing disease with a poor prognosis when left untreated, making the approval of acoramidis, which has demonstrated improved benefit on all-cause mortality and cardiovascular-related hospitalizations in as few as three months, a very important accomplishment for patients. We are pleased that people living with ATTR-CM will have access to another treatment option in the EU,” said Marianna Fontana, M.D., Ph.D., Professor of Cardiology and Honorary Consultant Cardiologist at the National Amyloidosis Centre, Division of Medicine, University College London. The approval in the EU is based on results of the pivotal ATTRibute-CM Phase 3 study of acoramidis, which showed clear benefits on cardiovascular outcomes. ATTRibute-CM evaluated the efficacy and safety of acoramidis in 632 participants with symptomatic ATTR-CM, associated with either wild-type or variant TTR who were randomized 2:1 to receive acoramidis or placebo for 30 months. The study met its primary clinical endpoints at month 30 by significantly reducing cardiovascular-related hospitalization, improving survival, and preserving functional capacity and quality of life for patients in need. “The EU approval of acoramidis is a significant advancement for patients living with ATTR-CM in need of new disease-modifying treatments for their condition,” said Dr Jonathan Fox, BridgeBio Cardiorenal Chief Medical Officer. “This approval would not have been possible without the commitment of the clinical trial participants and their families, and the dedicated support of the physicians and scientists involved in the clinical program. Alongside our able partners at Bayer we look forward to this new opportunity to serve ATTR-CM patients across the European Union.” Following EU approval, Bayer will launch acoramidis in the first half of 2025. Acoramidis was approved as Attruby™ by the U.S. FDA in November 2024 with a label specifying near-complete stabilization of TTR. As reported on January 13, BridgeBio has seen strong commercial momentum, with 430 patient prescriptions written by 248 physicians since the U.S. approval. In March 2024, BridgeBio and Bayer initiated a collaboration for acoramidis, which granted Bayer exclusive commercialization rights in the EU. Based on terms of the licensing agreement, BridgeBio will receive a $75 million milestone payment upon European Commission approval. BridgeBio will also receive royalties in a tiered structure beginning in the low-thirties percent on sales of acoramidis in the EU following initiation of commercialization efforts. Acoramidis is currently under review for approval by the Japanese Pharmaceuticals and Medical Devices Agency and the Brazilian Health Regulatory Agency . 1 Christoffersen M et al. Transthyretin Tetramer Destabilization and Increased Mortality in the General Population. JAMA Cardiol. 2024 Dec 4:e244102. About BEYONTTRA BEYONTTRA is an orally administered near-complete (≥90%) stabilizer of transthyretin (TTR) indicated for the treatment of wild-type or variant transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM). BEYONTTRA was generally well-tolerated. The most common side effects were mild and included diarrhea and abdominal pain that were resolved without drug discontinuation. For full prescribing information, please refer to the Summary of Product Characteristics (SmPC) which will be available on the European Medicines Agency (EMA) website once published. 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 . SOURCE: BridgeBio Pharma

German drugmaker Boehringer Ingelheim didn’t share any data behind the top-line result, instead promising that the efficacy and safety findings would be unveiled in the second quarter.\n Boehringer Ingelheim has cemented the potential of its idiopathic pulmonary fibrosis (IPF) drug with a second phase 3 win in a related lung disease leading the drugmaker to expand the indications it will seek FDA approval for.The FIBRONEER-ILD trial saw 1,178 patients with progressive pulmonary fibrosis (PPF) receive either a 9 mg or 18 mg dose of the PDE4B inhibitor nerandomilast or placebo twice a day for 52 weeks. The study hit its primary endpoint of demonstrating an absolute change from baseline in forced vital capacity—a measure of the volume of air that a patient can breathe out—Boehringer said in a Feb. 10 release.The German drugmaker didn’t share any data behind the top-line result, instead promising that the efficacy and safety findings would be unveiled in the second quarter.“Initial data readouts of the FIBRONEER trials support a generally consistent safety and tolerability profile when compared to the phase 2 IPF study, with overall adverse events comparable to those seen in the placebo group,” the company said.Armed with the latest results, Boehringer said it will request that FDA and global regulators approve nerandomilast as a treatment for PPF, a type of interstitial lung disease. The company has already said it will seek approval for nerandomilast in IPF after proclaiming a win in a phase 3 trial for that lung disease in September 2024. Again, the company opted to hold back any concrete data from that trial for later in this year.When it comes to managing IPF, physicians already have Boehringer’s Ofev and Roche’s Esbriet. However, those drugs only slow the progression of fibrosis, while attempts to produce molecules that further slow, or ideally stop, progression have failed to prove their worth.By targeting phosphodiesterase 4B (PDE4B), nerandomilast is meant to have a mechanistic advantage over the incumbent products. Targeting PDE4 drives anti-inflammatory and antifibrotic effects, but attempts to develop oral inhibitors of the enzyme in respiratory diseases have been hindered by class-related systemic adverse events such as diarrhea and headaches.“The positive FIBRONEER-ILD topline result shows the potential of nerandomilast in progressive pulmonary fibrosis,” Shashank Deshpande, Head of Human Pharma at Boehringer, said in the release. “The hope is that the safety and tolerability profile we are initially seeing could potentially help to reduce treatment challenges.”