Glatiramer Acetate

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。美国FDA的认证意味着产品的安全性和质量得到了权威性的认可和保证，能够为消费者提供更加可靠的产品，是产品品质与效果的全球最高标准证明，FDA一直致力于履行其促进和保护公众健康的使命。2024年1-5月FDA拒批了13款药物，小编整理如下：江苏恒瑞/HLB:“双艾”疗法5月17日，Elevar Therapeutics子公司HLB及其在中国的合作伙伴江苏恒瑞医药宣布收到FDA对于注射用卡瑞利珠单抗联合甲磺酸阿帕替尼片用于不可切除或转移性肝细胞癌患者的一线治疗的BLA申请的完整回复信（CRL），在CRL中FDA表示会对恒瑞提交的生产现场检查缺陷完整回复进行全面评估，以及由于部分国家的旅行限制，无法在审查周期内完成必需的生物学研究监测计划(BIMO)临床检查，因此该产品的BLA申请将被拒绝。对此，恒瑞表示将尽快重新提交申请。卡瑞利珠单抗（camrelizumab）是恒瑞医药研发的人源化抗PD-1单克隆抗体，于2019年5月在中国获批上市，此前已在肺癌、肝癌、食管癌、鼻咽癌以及淋巴瘤五大瘤种中获批了9个适应症。阿帕替尼（rivoceranib）是恒瑞医药开发的一款针对血管内皮生长因子受体（VEGFR）的小分子酪氨酸激酶抑制剂，于2014年10月在中国获批上市，目前有3个适应症获批，分别为单药用于晚期胃腺癌或胃食管结合部腺癌、既往接受过至少一线系统性治疗后失败或不可耐受的晚期肝细胞癌、联合卡瑞利珠单抗用于不可切除或转移性肝细胞癌。2021年4月，卡瑞利珠单抗联合阿帕替尼一线治疗不可切除或转移性肝细胞癌适应症获得FDA孤儿药资格。Dynavax：Heplisav-BDynavax Technologies 宣布 FDA 拒绝了其重组蛋白乙型肝炎疫苗用于在血液透析中患者的补充生物制品许可证申请。这家加州生物制药公司表示，它收到了监管机构关于其sBLA的完整回复函（CRL），其中包括来自119名接受血液透析的成人的四剂量Heplisav-B方案的I期HBV-24研究的临床免疫原性和安全性数据。根据CRL，“申请没有提供足够的数据来支持对有效性或安全性的全面评估。”FDA 认为该申请没有提供足够的数据来支持有效性或安全性的全面评估。CRL表示，HBV-24的数据不足，因为第三方临床试验现场运营商销毁了大约一半参加试验的受试者的数据源文件。该公司还透露，FDA发现单臂研究中的受试者总数“不足以评估四剂方案的安全性”。Dynavax在其新闻稿中表示，FDA拒绝其sBLA不会影响欧盟委员会于2023年10月批准血液透析患者四剂量方案的决定，或Heplisav-B在美国、欧盟和英国被批准用于预防所有已知乙型肝炎病毒亚型引起的成人感染的适应症。Abeona：pz-cel4月22日，Abeona Therapeutics宣布FDA针对其细胞疗法 prademagene zamikeracel (pz-cel，EB-101)的完整回复信 (CRL)，FDA拒绝了该疗法上市，并要求其提供治疗的有效信息，以及满足额外的CMC 要求才能批准申请。受此消息影响，Abeona股价大跌53%。Pz-cel是一种体外基因校正的自体细胞疗法，用于治疗RDEB患者。该疗法由表皮片组成，旨在将功能性COL7A1基因传递到患者自身的皮肤细胞中，以实现正常的VII型胶原蛋白表达，并促进伤口愈合。试验表明，pz-cel可以帮助治愈伤口，并减轻RDEB患者的疼痛。然而，FDA对其位于俄亥俄州克利夫兰的制造工厂进行检查，因 pz-cel 制造相关的问题，FDA驳回了pz-cel的上市申请，但没有要求提供额外的试验或数据来支持后续申请。pz-cel原定PDUFA 日期是2024年5月25日，现在将有所推迟。Supernus：SPN-8304月8日，FDA宣布Supernus Pharmaceuticals治疗帕金森病的药物SPN-830第二次被拒，原因是质量和设备问题。SPN-830是一种阿朴吗啡注射剂，用于持续治疗帕金森病（PD）的运动波动（间歇性发作）。受此影响，Supernus股价在盘前下跌了10%。CRL中表示有两个方面需要FDA进行更多审查。第一个问题是Supernus需要提供更多信息，包括有关产品质量的更多信息。Supernus指出最近向监管机构提交了更多的产品质量数据，但尚未得到审查。FDA 提出的另一个问题与输液设备的主文件有关。Supernus 表示，主文件是专有的，并计划与设备制造商讨论监管机构要求的信息和重新提交 NDA 所需的步骤。与此同时，Supernus公司表示，没有发现任何临床安全性或有效性问题需要获得批准。Vanda：Hetlioz3月6日，Vanda Pharmaceuticals宣布，已经收到FDA就Hetlioz（他司美琼）治疗失眠补充新药申请（sNDA）发出的完整回应函。FDA表示发现了标签和上市后要求/保证之外的缺陷，不能批准目前的sNDA。Vanda正在对其进行审查，并评估下一步行动。Hetlioz是一款褪黑素受体激动剂，2014年1月在美国获批治疗非24小时睡眠觉醒障碍。2020年12月，该产品拓展新适应症，获FDA批准治疗史密斯-马吉利综合征 (SMS) 夜间睡眠障碍。Viatris/Mapi Pharma：GA Depot3月11日，晖致（Viatris）和Mapi Pharma共同宣布收到FDA就GA Depot（醋酸格拉替雷，40mg）用于治疗复发型多发性硬化症的新药申请（NDA）发出的完整回复函（CRL）。关于FDA拒绝的具体细节很少，这两家公司仅表示，他们目前正在审查完整回复函，以更好地确定GA Depot 40的“适当下一步”。GA Depot 40的活性成分醋酸格拉替雷是一种免疫调节剂，1996年在美国获批用于治疗多发性硬化症（MS），商品名为Copaxone。2023年6月，格拉替雷在中国获批上市。GA Depot的NDA主要是基于一项III期研究的积极结果。该研究评估了GA Depot对比安慰剂治疗RMS患者的有效性、安全性和耐受性。结果显示，GA Depot组患者的年复发率相比安慰剂组降低了30.1%（P=0.0066）。Minerva：Roluperidone2月27日，Minerva Neurosciences宣布收到FDA就Roluperidone用于治疗精神分裂症阴性症状的新药申请（NDA）发出的完整回复函（CRL），表示拒批其精神分裂症新药。受此消息影响，Minerva股价大跌59%。在CRL中，FDA 指出了以下四点拒批理由：虽然MIN-101C03研究在主要疗效终点上显示出统计学意义，但其本身不足以确立实质性的有效性证据；提交的NDA缺乏有关同时服用抗精神病药物的数据；NDA材料缺乏证明Roluperidone对改善精神分裂症阴性症状具有临床意义的必要数据；在已提交的安全性数据中，至少服用12个月拟议剂量（64mg）Roluperidone的患者数量不足。为了解决这些缺陷，FDA规定Minerva必须至少再提交一项积极、充分和对照良好的研究，以支持Roluperidone治疗阴性症状的安全性和有效性。Minerva还必须提供额外的数据来证明Roluperidone与其它抗精神病药物联合用药的安全性和有效性，以进一步支持Roluperidone的有效性并证明拟议剂量的长期安全性。总结FDA在创新药的上市审批上日渐趋严，以高标准、高要求将多款创新药被拒之门外。FDA的拒批原因主要集中疗效、安全性、CMC问题和标签缺陷上，上市申请被拒除了影响产品的商业化进程外，也可能使企业遭受重大的股市打击，因此企业应审慎考虑FDA审批标准，减少碰壁几率，以期成功闯关FDA。参考资料：各公司官网

Pictured: A graphic showing figures on opposing coin stacks/Taylor Tieden for BioSpace Last year, empowered by new SEC reporting guidelines, BioSpace released its inaugural annual CEO pay gap report, looking at how much more top biopharma executives earned than their employees in 2022. Results showed that many biopharma executives earn more than 200 times what the company’s median employee makes. Looking at 2023 data, we found that little has changed. Despite investor dollars being hard to come by and the Biden administration pushing forward with its campaign to lower drug prices, the top biopharma firms still shelled out two orders of magnitude more money to CEOs than to median employees. Multiple companies have downsized their pipelines and operations, laying off thousands of workers across the industry. Some CEOs have even taken pay cuts to help the company’s bottom line. Famously, Pfizer’s Albert Bourla took a 35% reduction in compensation, with his pay dropping from $33 million in 2022 to $21.6 million last year. But while the ratio of Bourla’s salary to that of the company’s median employee lessened since 2022, he was still paid nearly 300 times the median salary, maintaining Pfizer’s spot near the top of BioSpace’s list. Big Biopharma Pay Gaps BioSpace highlights some of the largest ratios of CEO total compensation to median employee comp in 2023 1. Teva Pharmaceuticals | 398:1 CEO Richard Francis: $25,706,880 Median employee pay: $64,562 While CEO Richard Francis was not the highest-paid CEO in the industry in 2023, Teva’s employees made only a median of $64,562—the lowest on BioSpace’s top 9 list—granting the multinational company the top spot on the 2023 pay gap ranking. This is likely due in part to the fact that Teva is based in Israel, where the cost of living is lower than in the U.S. Teva, which filed a 2023 proxy statement with the SEC, is the only non-U.S. company included in this analysis. Teva had a strong 2023. The company made more than $15.8 billion, representing a 7% increase from its $14.9 billion revenue in the year prior. Mirroring this growth, the CEO compensation package jumped from $15.5 million in 2022—Kåre Schultz was the company’s chief at the time, before retiring in November 2022—to Francis’ total compensation of $25.7 billion in 2023. The cornerstone of Teva’s business is its generic products, which in 2023 brought in $3.48 billion, down 2% from 2022. Teva also saw declining sales for its multiple sclerosis therapy Copaxone and chronic lymphocytic leukemia chemotherapy Bendeka. These were offset by a 27% surge in the earnings of Austedo, its extended-release tablets for Huntington’s disease chorea and tardive dyskinesia. 2. Johnson & Johnson | 338:1 CEO Joaquin Duato: $28,422,037 Median employee pay: $84,000 With total compensation of $28.4 million, J&J head Joaquin Duato is the highest-paid CEO on this list, according to BioSpace’s analysis. Meanwhile, J&J’s median employee pay was comparatively low at $84,000, resulting in one of the industry’s widest pay gaps. Despite the expiration of key patent protections for its blockbuster antibody Stelara, J&J saw a 6.5% surge in revenues last year, which increased from almost $80 billion in 2022 to $85.16 billion in 2023. In turn, Duato received a large jump in compensation, which more than doubled from $13.1 million to $28.42 million—the highest pay hike of any CEO on BioSpace’s list. J&J’s growth was driven primarily by its cancer business, which grew by 10.5% to $17.7 billion in 2023. Stelara still reigned as the pharma’s most profitable asset, surging 11.7% to bring in $10.86 billion in sales. 3. Pfizer | 291:1 CEO Albert Bourla: $21,562,064 Median employee pay: $74,008 Despite his 35% pay cut, Pfizer’s Albert Bourla is still among the highest-paid CEOs in biopharma and earns nearly 300 times more than his company’s median employee does. Pfizer also has the second-lowest median employee pay in BioSpace’s ranking, once again contributing to the large pay gap ratio. Pfizer is among the pharma companies most severely affected by the dwindling COVID-19 market. In its full-year 2023 business report, the pharma posted a 42% decline, with revenues dropping from more than $100 billion in 2022 to $58.5 billion last year. In the third quarter of 2023, Pfizer recorded its first quarterly loss since 2019. To shore up its financial position, the company in October 2023 launched a sweeping cost-cutting initiative designed to save $3.5 billion through 2024. 4. Merck | 183:1 CEO Robert Davis: $20,273,287 Median employee pay: $110,827 At $20.2 million, Merck chief Robert Davis is one of the lowest-paid CEOs on this ranking, but he still got paid nearly 200 times more than the median employee in 2023. Merck owns Keytruda (pembrolizumab)—a PD-1 inhibitor indicated for several cancers—which was the industry’s top-selling asset last year, according to data analytics website Statista. In 2023, Keytruda’s sales grew 19% and brought in more than $25 billion, heavily contributing to Merck’s total revenue of $60.1 billion. 5. AbbVie | 169:1 CEO Richard Gonzalez: $25,661,972 Median employee pay: $151,991 Richard Gonzalez’s total compensation was nearly $25.7 million in 2023, a slight decrease from his pay of $26.2 million the year prior. This dip contributed to a smaller pay gap, with the ratio dropping from 224:1 to 169:1. AbbVie logged a total global net revenue of $54.3 billion in 2023, representing a 6.4% decrease from the year prior. The pharma attributed this decline to increasing biosimilar erosion for its blockbuster antirheumatic medication Humira. Currently there are at least five Humira biosimilars in the U.S. market. Despite increasing competition, Humira remained AbbVie’s best-performing asset last year, bringing in a worldwide total of $14.4 billion. 6. Eli Lilly | 168:1 CEO David Ricks: $26,565,732 Median employee pay: $157,937 With a total compensation of almost $26.6 million, Eli Lilly head David Ricks is the second most highly paid CEO on BioSpace’s list. This big paycheck heavily contributed to the pharma’s large pay gap, even though the median employee compensation of $157,937 was also relatively high. Lilly reported a full-year revenue of $34.1 billion in 2023, which corresponds to 20% growth, driven by the strong performance of its diabetes and obesity portfolio. The pharma’s type 2 diabetes drug Trulicity was its top asset, earning $7.1 billion last year, while Mounjaro, one of its fastest-growing products, raked in $5.2 billion. Despite only winning approval in November 2023, Lilly’s weight-loss treatment Zepbound still managed to bring in nearly $176 million. 7. Amgen | 136:1 CEO Robert Bradway: $22,643,650 Median employee pay: $166,322 At $166,322, Amgen had the second-highest median employee pay in 2023 of our top 9. In turn, despite a large compensation package of $22.6 billion for CEO Robert Bradway, the pharma found itself below some of its competitors in terms of pay gap. In 2023, Amgen posted nearly $28.2 billion in revenue, up from $26.3 billion in 2022. Much of this growth was driven by its postmenopausal osteoporosis therapy Evenity and acute lymphoblastic leukemia treatment Blincyto. The hyperlipidemia medication Repatha, which brought in $1.64 billion last year, also saw strong growth at 26%. Amgen’s best-selling asset in 2023 was the osteoporosis therapy Prolia, which earned over $4 billion. 8. Bristol Myers Squibb | 130:1 CEO Giovanni Caforio: $19,661,434 Median employee pay: $151,172 Before retiring in November 2023, former BMS chief Giovanni Caforio had a compensation package reaching almost $19.7 million, which is the lowest of the CEOs in BioSpace’s list. Meanwhile, the median employee pay at BMS last year was relatively high at $151,172, resulting in a comparatively small pay gap among these biopharma giants. Caforio was succeeded by former BMS COO Christopher Boerner. BMS brought in $45 billion in 2023, a 2% decline from its revenue in 2022. The pharma blamed the dip on the 39% plunge in sales of its multiple myeloma therapy Revlimid, which was only partially offset by the 10% jump in its cancer treatment Opdivo. BMS’ top asset last year was the anticoagulant Eliquis, which raked in more than $12.2 billion. 9. Gilead Sciences | 110:1 CEO: Daniel O'Day, $22,607,690 Median employee pay: $205,866 At over $205,000, Gilead’s median employee pay is the highest of all the companies on BioSpace’s top 9 list. Meanwhile, CEO Daniel O’Day brought in a relatively low total of $22.6 million. The pharma recorded a total global revenue of $27.1 billion in 2023, a slight drop from nearly $27.3 billion in 2022. Sales of Gilead’s COVID-19 antiviral treatment Veklury plunged 44% to $2.2 billion last year. The company made up for this drop through its HIV and oncology businesses, which grew by 6% and 37%, respectively. In its year-end report, the pharma revealed that its breast cancer therapy Trodelvy missed its primary endpoint in the Phase III EVOKE-01 study, failing to significantly improve overall survival versus docetaxel in non-small cell lung cancer. Pay Gaps Pervade Life Sciences Industries This year BioSpace’s analysis strictly focused on the top biopharma companies with SEC filings disclosing the pay gap ratio between CEO and median employee. It is worth noting that at least some foreign companies that don’t SEC forms, but for which we do have similar information, also had triple digit pay gaps. U.K.-based AstraZeneca, for example, reported a 182:1 ratio between its CEO’s remuneration and that of its median employee. This year’s list also excludes Viatris, which has not yet filed its proxy statement for 2023, but based on 2022 data would have topped the list with a ratio of 424:1. We also focused exclusively on biopharma companies this year, excluding service providers, financial firms and healthcare organizations. Many of these peripheral players would have topped the list otherwise. Bausch + Lomb, a consumer eye health company, would have easily claimed the top spot, with a pay gap ratio of almost 898:1. Volatility in Pay Gaps In the second year of doing this survey of CEO-employee pay gaps in biopharma, BioSpace noticed some extreme jumps in the data. Two interesting cases came from smaller biopharma companies that were eliminated from this year’s analysis due to their size, but wouldn’t have made the list anyway because their pay gaps fell considerably compared with 2022. While Sarepta Therapeutics and Biogen opened and closed last year’s top 20, with ratios of 494:1 and 182:1, respectively, those numbers were just 5:1 and 23:1 in 2023. Sarepta CEO Doug Ingram’s total comp was nearly $125 million in 2022, though his base salary was just over $740,000. The bulk of his compensation came from stock awards and options agreements. Without these extras, Ingram’s compensation fell to $1.66 million in 2023, comparable to 2021. Meanwhile, Biogen chief Christopher Viehbacher’s 2022 compensation was inflated by his $30.5-million sign-on package when he agreed to lead the pharma that November. Last year, Viehbacher’s pay was $4.1 million. Methodology In coming up with this report, BioSpace collected data from the SEC filings of the top U.S. biopharma companies by 2023 revenue to identify those firms with the widest pay gaps between the CEO and the median employee. We considered only those companies that filed Schedule 14a proxy statements reporting this information for 2023. Even still, the SEC allows a company to “select its methodology for identifying its median employee and that employee’s compensation,” as long as its methods are “reasonable.” As such, directly comparing pay gap ratios between companies could be inconclusive or misleading. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.