Topouzis Stavros, Papapetropoulos Andreas, Alexander Steve P H, Cortese-Krott Miriam, Kendall Dave A, Martemyanov Kirill, Mauro Claudio, Nagercoil Nithyanandan, Panettieri Reynold A, Patel Hemal H, Schulz Rainer, Stefanska Barbara, Stephens Gary J, Teixeira Mauro M, Vergnolle Nathalie, Wang Xin, Ferdinandy Péter
Department of Pharmacy, University of Patras, Patras, Greece.
Laboratory of Pharmacology, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.
Br J Pharmacol. 2025 Apr;182(7):1416-1445. doi: 10.1111/bph.17458. Epub 2025 Feb 19.
In the past year, the European Medicines Agency (EMA), the Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) authorised 53 novel drugs. While the 2024 harvest is not as rich as in 2023, when 70 new chemical entities were approved, the number of 'orphan' drug authorisations in 2024 (21) is similar to that of 2023 (24), illustrating the dynamic development of therapeutics in areas of unmet need. The 2024 approvals of novel protein therapeutics (15) and advanced therapy medicinal products (ATMPs, 6) indicate a sustained trend also noticeable in the 2023 new drugs reviewed in this journal last year (16 and 11, respectively). Clearly, the most striking characteristic of the 2024 drug yield is the creative pharmacological design, which allows these medicines to employ a novel approach to target a disease. Some notable examples are the first drug successfully using a 'dock-and-block' mechanism of inhibition (zenocutuzumab), the first approved drug for schizophrenia designed as an agonist of M/M muscarinic receptors (xanomeline), the first biparatopic antibody (zanidatamab), binding two distinct epitopes of the same molecule, the first haemophilia therapy that instead of relying on external supplementation of clotting factors, restores Factor Xa activity by inhibiting TFPI (marstacimab), or the first ever authorised direct telomerase inhibitor (imetelstat) that reprogrammes the oncogenic drive of tumour cells. In addition, an impressive percentage of novel drugs were first in class (28 out of 53 or 53% of the total) and a substantial number can be considered disease agnostic, indicating the possibility of future approved extensions of their use for additional indications. The 2024 harvest demonstrates the therapeutic potential of innovative pharmacological design, which allows the effective targeting of intractable disorders and addresses crucial, unmet therapeutic needs.
在过去一年中，欧洲药品管理局（EMA）、美国食品药品监督管理局（FDA）和英国药品和医疗产品监管局（MHRA）批准了53种新药。虽然2024年获批的新药数量不如2023年（当年有70种新化学实体获批）那么多，但2024年“孤儿”药的获批数量（21种）与2023年（24种）相近，这表明在未满足医疗需求领域，治疗方法正在蓬勃发展。2024年获批的新型蛋白质疗法（15种）和高级治疗药物产品（ATMPs，6种）表明这一持续趋势在去年本期刊回顾的2023年新药中也很明显（分别为16种和11种）。显然，2024年药物产出最显著的特点是创新性的药理设计，这使得这些药物能够采用新颖的方法来靶向疾病。一些值得注意的例子包括首个成功采用“对接并阻断”抑制机制的药物（泽诺库妥珠单抗）、首个被批准用于精神分裂症的设计为M/M毒蕈碱受体激动剂的药物（萨诺美林）、首个双特异性抗体（泽尼达妥单抗），它能结合同一分子的两个不同表位、首个血友病疗法，该疗法不是依靠外部补充凝血因子，而是通过抑制组织因子途径抑制物（TFPI）来恢复凝血因子Xa的活性（马司他昔单抗），或者首个获批的直接端粒酶抑制剂（艾美司他），它能重新编程肿瘤细胞的致癌驱动。此外，令人印象深刻的是，相当比例的新药属于同类首创（53种中的28种，占总数的53%），并且有相当数量的药物可被视为与疾病无关，这表明未来它们有可能获批用于更多适应症。2024年的新药收获展示了创新药理设计的治疗潜力，这种设计能够有效靶向难治性疾病并满足关键的、未满足的治疗需求。
