Galcanezumab-gnlm

Ajovy (fremanezumab-vfrm) Emgality (galcanezumab-gnlm) Nurtec ODT (rimegepant) Ubrelvy (ubrogepant) Vyepti (eptinezumab-jjmr) Hypertension The "Warnings and Precautions", "Adverse Reactions", "Patient Counseling Information", and "Patient Information" sections of the labeling were updated in March 2025 to include information about the risk of hypertension. Example: Ajovy labeling Apriso (mesalamine) Asacol (mesalamine) Asacol HD (mesalamine) Azulfidine (sulfasalazine) Azulfidine EN-Tabs (sulfasalazine) Canasa (mesalamine) Colazal (balsalazide disodium) Delzicol (mesalamine) Dipentum (osalazine sodium) Giazo (balsalazide disodium) Lialda (mesalamine) Rowasa (mesalamine) Pentasa (mesalamine) Severe cutaneous adverse reactions The Warnings and Precautions section of the labeling was updated November 2021 to include severe cutaneous adverse reactions. Example: Delzicol labeling Avastin (bevacizumab) Mvasi (bevacizumab-awwb) Zirabev (bevacizumab-bvzr) Pancreatitis FDA determined that no action is necessary at the time based on available information. Avastin (bevacizumab) Mvasi (bevacizumab-awwb) Zirabev (bevacizumab-bvzr) Anaphylactic shock The "Warnings and Precautions" section of the labeling was updated between September 2022 and February 2023 to include anaphylactoid/anaphylactic reactions. Example: Avastin labeling Ayvakit (avapritinib) Photosensitivity reaction The "Warnings and Precautions", "Adverse Reactions", "Patient Counseling Information", and "Patient Information" sections of the labeling were updated in March 2023 to include information about photosensitivity. Ayvakit labeling Azacitidine Onureg (azacitidine) Vidaza (azacitidine) Generic products containing azacitidine Pericarditis The "Adverse Reactions" section of the labeling was updated between September 2022 and June 2023 to include pericarditis. Example: Vidaza labeling FDA determined that no action is necessary at the time based on available information for Onureg. Bavencio (avelumab) Imfinzi (durvalumab) Libtayo (cemiplimab-rwlc) Keytruda (pembrolizumab) Opdivo (nivolumab) Tecentriq (atezolizumab) Yervoy (ipilimumab) Tumour lysis syndrome FDA determined that no action is necessary at the time based on available information. Cymbalta (duloxetine hydrochloride) Drizalma Sprinkle (duloxetine hydrochloride) Generic products containing duloxetine hydrochloride Anosmia, Hyposmia This issue is posted as two individual newly identified safety signal (NISS) entries in the January-March 2022 quarter, to reflect the focus on the potential signals of anosmia and hyposmia, separately. Darzalex (daratumumab) Darzalex Faspro (daratumumab and hyaluronidase-fihj) Blood stem cell transplant failure FDA determined that no action is necessary at the time based on available information. Dipeptidyl peptidase-4 (DPP-4) inhibitors Glyxambi (empagliflozin and linagliptin) Janumet (metformin hydrochloride and sitagliptin phosphate) Janumet XR (metformin hydrochloride and sitagliptin phosphate) Jentadueto (linagliptin and metformin hydrochloride) Jentadueto XR (linagliptin and metformin hydrochloride) Kazano (alogliptin and metformin hydrochloride) Kombiglyze XR (metformin hydrochloride and saxagliptin) Nesina (alogliptin) Onglyza (saxagliptin) Oseni (alogliptin and pioglitazone) Steglujan (ertugliflozin and sitagliptin) Tradjenta (linagliptin) Trijardy XR (empagliflozin, linagliptin and metformin hydrochloride) Qtern (saxagliptin and dapagliflozin) Generic products containing dipeptidyl peptidase-4 inhibitors Tubulointerstitial nephritis The "Adverse Reactions" section of the labeling was updated between March 2022 and June 2022 for products containing alogliptin and sitagliptin to include tubulointerstitial nephritis. Example: Janumet labeling FDA determined that no action is necessary for products containing linagliptin and saxagliptin at the time based on available information. *An administrative error resulted in the omission of Januvia from the list of product names after the initial quarterly report was posted. Dupixent (dupilumab) Angioedema The "Warnings and Precautions" and "Adverse Reactions" sections of the labeling were updated in December 2021 to include angioedema. Dupixent labeling Glucagon-like peptide-1 (GLP-1) analogues Adlyxin (lixisenatide) Bydureon (exenatide) Bydureon BCise (exenatide) Byetta (exenatide) Ozempic (semaglutide) Rybelsus (semaglutide) Saxenda (liraglutide) Soliqua 100/33 (insulin glargine and lixisenatide injection) Trulicity (dulaglutide) Victoza (liraglutide) Wegovy (semaglutide) Xultophy 100/3.6 (insulin degludec and liraglutide injection) Generic products containing glucagon-like peptide-1 analogues Gallbladder related disorders The "Warnings and Precautions", "Adverse Reactions", and "Patient Counseling Information" sections of the GLP-1 analogues labeling were updated between March 2022 and June 2022 to include information about acute gallbladder disease. Example: Adlyxin labeling FDA has determined that the last approved labeling for Saxenda and Wegovy is adequately labeled for acute gallbladder disease, and that no further regulatory action is needed at this time. Gonadotropin releasing hormone (GnRH) analogues Fensolvi (leuprolide acetate) Lupron Depot-PED (leuprolide acetate) Supprelin LA (histrelin acetate) Synarel (nafarelin acetate) Triptodur (triptorelin) Idiopathic intracranial hypertension The "Warnings", "Precautions", and "Adverse Reactions" sections of the labeling were updated in April 2022 to include idiopathic intracranial hypertension. Example: Fensolvi labeling Jakafi (ruxolitinib phosphate) Herpes simplex virus (HSV) reactivation and/or disseminated HSV The "Dosage and Administration", "Warnings and Precautions", and "Adverse Reactions" sections of the labeling were updated in January 2023 to include information about herpes simplex and herpes zoster infections. Jakafi labeling Ibrance (palbociclib) Kisqali (ribociclib) Kisqali Femara Co-Pack (letrozole and ribociclib) Embolic and thrombotic events, venous The "Adverse Reactions" section of the Ibrance labeling was updated in December 2024 to include venous thromboembolism. Ibrance labeling FDA determined that no action is necessary at the time for Kisqali and Kisqali Femara Co-Pack based on available information. Ocrevus (ocrelizumab) Myocardial infarction FDA determined that no action is necessary at the time based on available information. Potassium Chloride Product preparation error The “Warnings” section of the labeling was updated in December 2022 to include information about fatal cardiac adverse reactions with intravenous administration of undiluted potassium chloride. Praxbind (idarucizumab) Wrong dose errors The carton labeling and "Dosage and Administration" sections of the labeling were revised in February 2022 to clarify the number of vials included in each carton and the recommended dosing. Praxbind labeling Qbrexza (glycopyrronium tosylate) Accidental exposure to product The container label, carton labeling, "Dosage and Administration", "Warnings and Precautions", "Patient Counseling Information", and "Patient Information" sections of the labeling were updated in October 2022 to include information about accidental exposure. Qbrexza labeling Qbrexza (glycopyrronium tosylate) Urinary retention The “Warnings and Precautions”, “Adverse Reactions”, and “Patient Counseling Information” sections of the labeling were updated in October 2022 to include information about new or worsening urinary retention. Qbrexza labeling Sodium-glucose cotransporter-2 (SGLT-2) inhibitors Farxiga (dapagliflozin) Glyxambi (empagliflozin and linagliptin) Invokamet (canagliflozin and metformin hydrochloride) Invokamet XR (canagliflozin and metformin hydrochloride) Invokana (canagliflozin) Jardiance (empagliflozin) Qtern (saxagliptin and dapagliflozin) Steglatro (ertugliflozin) Steglujan (ertugliflozin and sitagliptin) Segluromet (ertugliflozin and metformin hydrochloride) Synjardy (empagliflozin and metformin hydrochloride) Synjardy XR (empagliflozin and metformin hydrochloride) Trijardy XR (empagliflozin, linagliptin and metformin hydrochloride) Xigduo XR (dapagliflozin and metformin) Generic products containing sodium-glucose cotransporter-2 (SGLT-2) inhibitors Tubulointerstitial nephritis FDA determined that no action is necessary at the time based on available information. Somatostatin Receptor Imaging Agents Detectnet (copper Cu-64 dotatate injection) Gallium Dotatoc (GA 68) Octreoscan (Indium In 111 Pentetreotide) Netspot (Gallium GA 68 Dotatate) Hypersensitivity The "Warnings and Precautions" and "Adverse Reactions" sections of the labeling were updated in December 2021 to include hypersensitivity reactions. Example: Netspot labeling Stromectol (ivermectin) Generic products containing ivermectin Off label use FDA determined that no action is necessary at the time based on available information. Stromectol (ivermectin) Generic products containing ivermectin Neurotoxicity The "Warnings", "Adverse Reactions", and "Overdosage" sections of the labeling were updated in March 2022 to include neurotoxicity. Example: Stromectol labeling Sunosi (solriamfetol hydrochloride) Hypersensitivity FDA determined that no action is necessary at the time based on available information. Vivitrol (naltrexone) Incorrect route of product administration The container label (vial), carton labeling, "Dosage and Administration", "Warnings and Precautions", and "Description", sections of the labeling were revised in September 2022 to emphasize the appropriate route and site of administration. Vivitrol labeling Xcopri (cenobamate) Psychiatric disorders The "Adverse Reactions" section of the labeling was updated in June 2022 to include psychiatric disorders. Xcopri labeling Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

编者按：2025年，药明康德迎来创立25周年的重要里程碑。值此契机，我们向所有与我们共同书写产业变革篇章的科学家、医药人和投资者致以衷心感谢与诚挚敬意，也特别推出“致敬时代”系列，回顾全球同仁如何借助科学与合作的力量，不断拓展治疗边界、改善患者命运。 四分之一个世纪的坚守，只为加速每一款新药的诞生。下一个25年，我们将继续心怀感恩与敬畏，依托独特的CRDMO模式，与全球伙伴携手同行，共赴健康未来。 偏头痛影响着全球超10亿人。这是一种严重的神经系统疾病，患者在疾病发作时十分痛苦，症状包括剧烈的搏动性反复头痛，恶心呕吐、头晕、对声光触觉气味极度敏感等，部分患者甚至会在这种痛苦症状中度过数日。长期发作和对复发的恐惧，还导致大量患者出现抑郁、焦虑和睡眠障碍，严重者达到致残级别。根据2019年全球疾病负担研究（GBD2019）数据，偏头痛是全球第二大致残性疾病，在年轻女性（15~49岁）中更是致残的首要原因。 近几十年来，偏头痛治疗领域迎来重大突破，尤其是降钙素基因相关肽（CGRP）类药物的出现，开启了偏头痛治疗的新纪元，更为无数患者带来“新生”。 作为全球医药及生命科学行业值得信赖的合作伙伴和重要贡献者，药明康德在25年发展历程中，见证了CGRP类药物从实验室到临床的突破历程，更通过提供一体化、端到端的新药研发和生产服务，助力全球合作伙伴加速包括偏头痛在内的创新疗法的上市进程，造福病患。今天这篇文章将再次回望科学家攻坚偏头痛的历程，向为这一领域付出努力和心血的所有人致敬。 图片来源：123RF 从疾病发现，到曲折反复的科学探索 偏头痛最早的记载可追溯至公元前3000年左右的美索不达米亚诗歌中，当时其“带有抽疼感的头痛”的特征已被捕捉。可惜科学的曙光却迟迟未至，在之后漫长的时光长河里，人类对其本质的探索一度踟蹰不前。 直到17世纪，血管学假说和神经源假说相继被提出，才开启了人们对偏头痛的科学认知。然而科学的进展总是曲折反复，随着研究的深入，这两种学说都遭到不同程度的挑战。此后百余年间，关于偏头痛病因的研究处于僵局，研究者们转而将精力投入到对偏头痛的治疗探索中。 18世纪中后期，麦角菌被发现具有促进血管收缩、肌肉痉挛、麻痹神经的作用。之后，麦角胺药物开始被应用于偏头痛治疗。尽管这类药物有一系列不良反应，但它们的确减少了患者的疼痛。 麦角胺类药物作为血管收缩剂治疗偏头痛被率先写入英国的教科书，也使得血管学假说一度备受认可。上世纪后半叶，用于偏头痛治疗的曲坦类药物诞生。相比之下，曲坦类药物通过激活血清素（5-HT，一种血管收缩剂）受体促进血管收缩，以缓解偏头痛症状，其高选择性使其可避免一些潜在不良反应，因而成为偏头痛治疗的重要选择。 上世纪70年代，还有多种用于治疗心脏病、癫痫和抑郁症的药物（如β受体阻滞剂）被意外发现能预防偏头痛。研究表明，它们通过降低大脑皮层和疼痛通路的兴奋性来起作用。后来，FDA先后批准了多种与此有关的药物用于偏头痛治疗。 这些药物共同构成了偏头痛患者的治疗选择，且目前依然在偏头痛临床治疗中发挥着重要作用。但这些药物仅对部分患者起效，并伴随着一系列不良反应，患者仍然缺少一款“量身定制”的特效药物。开发新型特异性抗偏头痛药物迫在眉睫。 图片来源：123RF 数十年接力，发现偏头痛关键机制  问题又回到了偏头痛疾病本身——揭示偏头痛发作机制，才能为开发新疗法打开关键突破口。上世纪70年代，这一领域终于迎来重大突破。 1975年前后，来自哈佛医学院麻省总医院的Michael Moskowitz教授及其团队研究证明，偏头痛发作涉及两个关键因素的相互作用：三叉神经与脑膜及其相关血管。Moskowitz教授提出：当三叉神经纤维被激活时，会释放化学信号使脑膜血管扩张，从而引发局部炎症并最终导致剧烈头痛。他随后用“三叉神经血管系统”这一术语来描述三叉神经、脑膜血管与中枢神经系统之间的关联。但彼时尚无法明确三叉神经释放的这种“化学信号”的具体成分。 几乎同一时期，来自隆德大学的Lars Edvinsson教授团队首次在颅内血管系统中检测到一种新型神经肽——血管活性肠肽，这是一种强效血管舒张剂。随后十年间，大量在脑血管神经支配中起作用的神经肽被鉴定出来，其中包括CGRP。Lars Edvinsson教授团队也进一步研究证实，三叉神经节中超半数神经元含有CGRP，并提出“CGRP参与偏头痛发作病理生理过程”的假说。 这一假说在他与当时在澳大利亚亨利王子医院（Prince Henry Hospital）神经内科工作的Peter Goadsby博士开展的合作研究中获得了确证。1990~1994年间，他们合作研究发现：CGRP是三叉神经痛通路中的一个关键递质，在偏头痛发作时选择性释放。他们的研究首次证实，CGRP在偏头痛中起着至关重要的作用，这为后来治疗偏头痛的CGRP拮抗剂类药物的出现奠定了基础。此外，1990年前后，更多研究者的发现也陆续为偏头痛的机制和治疗提供更多的佐证。比如，英国药理学家Patrick Humphrey博士发现的5-HT受体激动剂舒马曲坦可阻断CGRP从三叉神经节释放的过程，为这类曲坦类药物能够治疗偏头痛提供了更多的证据。 来自哥本哈根大学的Jes Olesen教授及其团队为CGRP从实验室走向临床补上最后一环，他们通过实验证明：外源性CGRP可诱发偏头痛患者发作，确立了CGRP在触发偏头痛中的因果关系，随后进一步证实CGRP阻断剂能有效治疗偏头痛。 目前已经知道，CGRP是由37个氨基酸组成的神经肽，存在于神经系统中，是一种强效的血管舒张剂和脑血管痛觉调节物质。使用CGRP靶向药物阻断CGRP或其受体，可用于减轻偏头痛的症状。 图片来源：The Brain Prize官网 正是这些神经学家的共同努力，奠定了CGRP在偏头痛中的临床研究基础。此后数年，这些基础研究突破激发了业界对CGRP靶向药物的研发热情，也开启了偏头痛研究与治疗的新纪元。自2018年起，FDA陆续批准了多款CGRP靶向药物，创新疗法的到来显著改善了众多患者的生活质量。在有公开记载的治疗案例中，大量偏头痛患者认为这类药物令他们“重获新生”。 2021年，素有“神经科学领域的诺贝尔奖”之称的“The Brain Prize”（大脑奖）将荣誉授予了Lars Edvinsson教授、Peter Goadsby教授、Michael Moskowitz教授和Jes Olesen教授。颁奖词中写道，他们关于偏头痛的研究完美诠释了“从临床到实验室再回归临床”的转化医学范式，且已产生切实的临床效益。 靶向药物诞生，偏头痛治疗迎来新变革 CGRP通路的发现和验证，使得偏头痛疗法的开发进入了新阶段。2004年初，《新英格兰医学杂志》发表了一项CGRP受体拮抗剂BIBN 4096 BS治疗急性偏头痛的临床研究结果。公开资料显示，这是最早进入临床开发阶段的CGRP拮抗剂类药物之一。此后，多款CGRP靶向小分子和抗体类药物陆续进入临床。 相比于小分子CGRP靶向疗法，CGRP靶向抗体疗法更早实现获批上市突破。2018年5月，安进（Amgen）旨在阻断CGRP受体的单抗药物erenumab成为FDA批准的首款治疗成人偏头痛的预防性治疗药物。之后的两年内，又有3款CGRP类单抗疗法接连获批，分别是梯瓦（Teva）的fremanezumab、礼来（Eli Lilly and Company）的galcanezumab和丹麦灵北（Lundbeck）的eptinezumab。由于较长的半衰期，抗体药物可以实现每月甚至每三个月一次给药，作为偏头痛的预防性治疗手段，在降低偏头痛发作频率和减少头痛天数方面疗效显著。 小分子CGRP受体拮抗剂的研发历程历经曲折，也很快取得突破。在首代化合物因长期用药下的肝脏不良反应问题而研发受阻后，经结构修饰与优化后的第二代化合物成功克服了这一缺陷，其安全性得到了显著提升。2019年，FDA批准了艾尔建（Allergan，现在已被艾伯维[AbbVie]收购）公司的小分子CGRP受体拮抗剂ubrogepant用于治疗急性偏头痛，为患者带来口服治疗选择。两年后，艾伯维另一款口服CGRP受体拮抗剂atogepant也获FDA批准，用于成人发作性偏头痛预防性治疗，并在2023年再次获批用于预防性治疗成人慢性偏头痛。 与此同时，研发人员也在进一步优化这类药物的用药方式。比如辉瑞（Pfizer）通过收购Biohaven所获得的rimegepant于2020年获批，成为首款获FDA批准的拥有快速口腔崩解片剂型的CGRP受体小分子拮抗剂，它能够让患者在1小时内恢复正常功能。同样来自辉瑞的zavegepant，于2023年成为FDA批准的用于急性治疗偏头痛成人患者的首款CGRP受体拮抗剂鼻内喷剂，它可在15分钟内快速起效。 图片来源：123RF 除CGRP靶向药物外，研究人员仍在不断深入探索偏头痛的更多发病机制。例如，曲坦类药物后来被发现可以通过抑制由三叉神经激活诱导的CGRP释放，从而缓解偏头痛。2019年，Dr. Reddy’s Laboratories和其下属公司Promius Pharma开发的曲坦类药物舒马曲坦的鼻喷雾剂sumatriptan获FDA批准用于急性偏头痛治疗，该创新剂型可加速药物吸收，迅速缓解疼痛。同年获FDA批准的lasmiditan则是一种5-HT1F受体激动剂，作为首个获FDA批准的“地坦”（ditans）类药物，与作用于5-HT1B/1D受体的曲坦类药物不同，它不会激活5-HT1B受体，无血管收缩作用，因此对伴有心血管疾病的偏头痛患者来说更为安全。 目前，还有多个新兴靶点陆续被发现具有偏头痛治疗或预防潜力，部分相关产品已经进入临床研究。例如钙离子通道TRPM3，其参与神经炎性疼痛信号传递；引发偏头痛的潜在介质PACAP，其水平上升可诱发偏头痛发作；以及GABAA受体，研究表明调节其抑制作用可能对偏头痛治疗具有积极影响等。 坚持创新和合作，继续为驱散疾病阴霾砥砺前行 从古代扑朔迷离的“抽疼感”，到上世纪90年代CGRP被确定为偏头痛治疗靶点，从2000年世纪之交开启CGRP类药物的研发，到如今多款靶向药物获批造福患者，人类对抗偏头痛的征程已经走过了漫长的道路，并取得了突破性的成果。 不过，当下人们与偏头痛这一“紧箍咒”的较量仍将继续。CGRP靶向药物等现有药物仍然不能完全治愈偏头痛，现有研究也未能完整阐明偏头痛患者在头痛前出现神经性先兆等独特症状，这一领域仍然存在未解之谜和未满足的医疗需求，等待科研人员去突破。 作为医药创新的赋能者，药明康德也一如既往地通过一体化、端到端的CRDMO研发平台，提供从早期药物发现和研究、开发到商业化生产的全面服务，助力全球合作伙伴加速包括偏头痛在内的各类神经系统疾病创新疗法的研发进程，让更多突破性的疗法造福患者。 例如在偏头痛/疼痛领域，CGRP受体属于G蛋白偶联受体（GPCR）家族，后者是哺乳动物中最大的膜蛋白家族，也是药物开发的重要靶点。公开信息显示，药明康德生物学业务平台拥有丰富的GPCR蛋白生产经验，突破了难以获取稳定、纯净且均质的膜蛋白的瓶颈，也给后续结晶和冷冻电镜样品制备铺平了道路。该平台拥有超过15年的结构生物学样品制备与结构解析经验，为靶向GPCR的药物研发提供了强有力的支持。药明康德生物学业务平台还建立了多种临床前疼痛模型，能够满足急性与慢性炎症性疼痛、术后疼痛、急性伤害性感受、慢性神经性疼痛、纤维肌痛样疼痛和骨关节炎等领域的各种药物研发需求，为全球合作伙伴提供多样化、一体化的疼痛模型服务，助力开发包括CGRP靶点在内的各种治疗药物。 在这场人类与偏头痛的漫长博弈中，我们相信科学创新的光芒，以及合作的力量终将驱散疼痛的阴霾。药明康德也期待与业界的各位同仁一道携手共进，早日为更多的患者缓解病痛，带来更多“生”的希望。 参考资料： [1] The BRAIN PRIZE官网. Retrieved August 20, 2025, from https://brainprize.org/winners/migraine-2021 [2] Olesen et al. (2004) Calcitonin Gene–Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine.The New England Journal of Medicine. Doi:10.1056/NEJMoa030505 [3] Paemeleire, et al. (2025) Calcitonin gene-related peptide-targeted therapy in migraine: current role and future perspectives. Lancet.doi: 10.1016/S0140-6736(25)00109-6. [4] Steiner et al. (2020) Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. J Headache Pain, doi: https://doi.org/10.1186/s10194-020-01208-0 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新