vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2024-14-1-14-28vedomostiregmed-579Research ArticleИННОВАЦИОННЫЕ ЛЕКАРСТВЕННЫЕ ПРЕПАРАТЫINNOVATIVE MEDICINAL PRODUCTSГлобальный спектр разработки инновационных лекарственных препаратов: описательный обзорGlobal Pipeline of Innovative Medicinal Products: A Narrative Reviewhttps://orcid.org/0000-0003-4891-973XМеркуловВ. А.MerkulovV. A.

Меркулов Вадим Анатольевич, д-р мед. наук, профессор

Петровский б-р, д. 8, стр. 2, Москва, 127051

Vadim A. Merkulov, Dr. Sci. (Med.), Professor

8/2 Petrovsky Blvd, Moscow 127051

Merkulov@expmed.ruhttps://orcid.org/0000-0002-9080-332XЯгудинаР. И.YagudinaR. I.

Ягудина Роза Исмаиловна, д-р фарм. наук, профессор

Петровский б-р, д. 8, стр. 2, Москва, 127051

Roza I. Yagudina, Dr. Sci. (Pharm.), Professor

8/2 Petrovsky Blvd, Moscow 127051

Yagudina@expmed.ruhttps://orcid.org/0000-0002-6896-2842СерпикВ. Г.SerpikV. G.

Серпик Вячеслав Геннадьевич, канд. фарм. наук, доцент

Трубецкая ул., д. 8, стр. 2, Москва, 119991

Vyacheslav G. Serpik, Cand. Sci. (Pharm.), Associate Professor

8/2 Trubetskaya St., Moscow 119991

Serpik.vyacheslav@gmail.comФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет им. И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation2024270220241411428Copyright © Меркулов В.А., Ягудина Р.И., Серпик В.Г., 20242024Меркулов В.А., Ягудина Р.И., Серпик В.Г.Merkulov V.A., Yagudina R.I., Serpik V.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/579АКТУАЛЬНОСТЬ

АКТУАЛЬНОСТЬ. Быстрый рост ассортимента лекарственных средств глобального фармацевтического рынка предопределяет актуальность периодического обзора спектра инновационных лекарственных средств и продуктов, находящихся на различных стадиях разработки.

ЦЕЛЬ

ЦЕЛЬ. Определение основных тенденций глобальных разработок инновационных лекарственных средств.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Представлены данные, характеризующие ценность и терапевтический эффект инновационных лекарственных препаратов, отражены современные подходы к регистрации и проблемы роста стоимости инновационных лекарственных препаратов. Описательный обзор проведен с использованием методов информационного поиска, контент-анализа и сканирования горизонтов. Дано описание глобального фармацевтического пайплайна как в целом, так и по отдельным направлениям по состоянию на II полугодие 2023 г. Выявлено, что в разработке находятся более 21 тыс. фармацевтических продуктов, из которых на поздних стадиях разработки (от клинических исследований III фазы до регистрации) находится около 23%, среди показаний к применению преобладает направление «Онкология и онкогематология». Отдельно рассмотрены инновации в области лекарственных препаратов для лечения болезни Альцгеймера, а также генной, клеточной и РНК-терапии.

ВЫВОДЫ

ВЫВОДЫ. Значительный объем инновационных лекарственных препаратов, находящихся на различных этапах разработки, с высокой вероятностью может изменить существующие подходы к терапии, профилактике и диагностике заболеваний, что с учетом возрастающей стоимости инновационных лекарственных препаратов подчеркивает важность внедрения в отечественную систему здравоохранения прогнозирования, например с использованием метода сканирования горизонтов.

SCIENTIFIC RELEVANCE

SCIENTIFIC RELEVANCE. The rapid expansion of the range of medicines in the global pharmaceutical market determines the importance of periodically reviewing the range of innovative medicines and products at various stages of development.

AIM

AIM. This study aimed to determine the main trends in the development of innovative medicines.

DISCUSSION

DISCUSSION. This review presents information on the therapeutic effects and value of innovative medicinal products, outlines current approaches to their authorisation, and addresses the increase in their costs. The authors used information search, content analysis, and horizon scanning methods to prepare this narrative review. The review describes the global pharmaceutical pipeline for the second half of 2023, both generally and by specific aspects. The authors determined that over 21,000 pharmaceutical products were in development at the time, with approximately 23% of those in the later stages of development (from phase III clinical trials to the registration stage). The predominant indications for use were cancers. The authors separately reviewed innovations in the treatment of Alzheimer’s disease, as well as gene, cell, and RNA therapies.

CONCLUSIONS

CONCLUSIONS. A significant number of innovative pipeline medicines have a high likelihood of changing the landscape of current approaches to disease treatment, prevention, and diagnosis. With the rising costs of innovative medicinal products, the potential for change underscores the importance of introducing predictive tools, such as horizon scanning, into the national healthcare system.

инновационные лекарственные препаратыстоимость лекарственных препаратовценность лекарственных препаратовпайплайнболезнь Альцгеймерагенная терапияклеточная терапияРНК-терапияinnovative medicinal productscost of medicinal productsvalue of medicinal productspipelineAlzheimer’s diseasegene therapycell therapyRNA therapyРабота выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056-0002624-00 на проведение прикладных научных исследований (номер государственного учета НИР 124022200093-9)The study reported in this publication was carried out as part of publicly funded research project No. 056-00026-24-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D reporting No. 124022200093-9)ReferencesVignali V, Hines PA, Cruz AG, Ziętek B, Herold R. Health horizons: future trends and technologies from the European Medicines Agency’s horizon scanning collaborations. Front Med (Lausanne). 2022;9:1064003. https://doi.org/10.3389/fmed.2022.1064003Vignali V, Hines PA, Cruz AG, Ziętek B, Herold R. Health horizons: future trends and technologies from the European Medicines Agency’s horizon scanning collaborations. Front Med (Lausanne). 2022;9:1064003. https://doi.org/10.3389/fmed.2022.1064003Adedeji WA. The treasure called antibiotics. Ann Ib Postgrad Med. 2016;14(2):56–7. PMID: 28337088Adedeji WA. The treasure called antibiotics. Ann Ib Postgrad Med. 2016;14(2):56–7. PMID: 28337088Buxbaum JD, Chernew ME, Fendrick AM, Cutler DM. Contributions of public health, pharmaceuticals, and other medical care to US life expectancy changes, 1990–2015. Health Aff (Millwood). 2020;39(9):1546–56. https://doi.org/10.1377/hlthaff.2020.00284Buxbaum JD, Chernew ME, Fendrick AM, Cutler DM. Contributions of public health, pharmaceuticals, and other medical care to US life expectancy changes, 1990–2015. Health Aff (Millwood). 2020;39(9):1546–56. https://doi.org/10.1377/hlthaff.2020.00284Lichtenberg FR. The effect of pharmaceutical innovation on longevity: evidence from the U.S. and 26 high-income countries. Econ Hum Biol. 2022;46:101124. https://doi.org/10.1016/j.ehb.2022.101124Lichtenberg FR. The effect of pharmaceutical innovation on longevity: evidence from the U.S. and 26 high-income countries. Econ Hum Biol. 2022;46:101124. https://doi.org/10.1016/j.ehb.2022.101124Lichtenberg FR. The impact of new (orphan) drug approvals on premature mortality from rare diseases in the United States and France, 1999–2007. Eur J Health Econ. 2013;14(1):41–56. https://doi.org/10.1007/s10198-011-0349-4Lichtenberg FR. The impact of new (orphan) drug approvals on premature mortality from rare diseases in the United States and France, 1999–2007. Eur J Health Econ. 2013;14(1):41–56. https://doi.org/10.1007/s10198-011-0349-4MacEwan JP, Dennen S, Kee R, Ali F, Shafrin J, Batt K. Changes in mortality associated with cancer drug approvals in the United States from 2000 to 2016. J Med Econ. 2020;23(12):1558–69. https://doi.org/10.1080/13696998.2020.1834403MacEwan JP, Dennen S, Kee R, Ali F, Shafrin J, Batt K. Changes in mortality associated with cancer drug approvals in the United States from 2000 to 2016. J Med Econ. 2020;23(12):1558–69. https://doi.org/10.1080/13696998.2020.1834403Manns MP, Maasoumy B. Breakthroughs in hepatitis C research: from discovery to cure. Nat Rev Gastroenterol Hepatol. 2022;19(8):533–50. https://doi.org/10.1038/s41575-022-00608-8Manns MP, Maasoumy B. Breakthroughs in hepatitis C research: from discovery to cure. Nat Rev Gastroenterol Hepatol. 2022;19(8):533–50. https://doi.org/10.1038/s41575-022-00608-8Campollo O, Amaya G, McCormick PA. Milestones in the discovery of hepatitis C. World J Gastroenterol. 2022;28(37):5395–402. https://doi.org/10.3748/wjg.v28.i37.5395Campollo O, Amaya G, McCormick PA. Milestones in the discovery of hepatitis C. World J Gastroenterol. 2022;28(37):5395–402. https://doi.org/10.3748/wjg.v28.i37.5395Krupa D, Czech M, Chudzyńska E, Koń B, Kostera-Pruszczyk A. Real world evidence on the effectiveness of nusinersen within the national program to treat spinal muscular atrophy in Poland. Healthcare. 2023;11(10):1515. https://doi.org/10.3390/healthcare11101515Krupa D, Czech M, Chudzyńska E, Koń B, Kostera-Pruszczyk A. Real world evidence on the effectiveness of nusinersen within the national program to treat spinal muscular atrophy in Poland. Healthcare. 2023;11(10):1515. https://doi.org/10.3390/healthcare11101515Berglund A, Berkö S, Lampa E, Sejersen T. Survival in patients diagnosed with SMA at less than 24 months of age in a population-based setting before, during and after introduction of nusinersen therapy. Experience from Sweden. Eur J Paediatr Neurol. 2022;40:57–60. https://doi.org/10.1016/j.ejpn.2022.07.005Berglund A, Berkö S, Lampa E, Sejersen T. Survival in patients diagnosed with SMA at less than 24 months of age in a population-based setting before, during and after introduction of nusinersen therapy. Experience from Sweden. Eur J Paediatr Neurol. 2022;40:57–60. https://doi.org/10.1016/j.ejpn.2022.07.005Beakes-Read G, Neisser M, Frey P, Guarducci M. Analysis of FDA’s accelerated approval program performance December 1992 — December 2021. Ther Innov Regul Sci. 2022;56(5):698–703. https://doi.org/10.1007/s43441-022-00430-zBeakes-Read G, Neisser M, Frey P, Guarducci M. Analysis of FDA’s accelerated approval program performance December 1992 — December 2021. Ther Innov Regul Sci. 2022;56(5):698–703. https://doi.org/10.1007/s43441-022-00430-zLakdawalla DN, Doshi JA, Garrison LP Jr, Phelps CE, Basu A, Danzon PM. Defining elements of value in health care — A health economics approach: An ISPOR Special Task Force Report. Value Health. 2018;21(2):131–9. https://doi.org/10.1016/j.jval.2017.12.007Lakdawalla DN, Doshi JA, Garrison LP Jr, Phelps CE, Basu A, Danzon PM. Defining elements of value in health care — A health economics approach: An ISPOR Special Task Force Report. Value Health. 2018;21(2):131–9. https://doi.org/10.1016/j.jval.2017.12.007Franken M, Stolk E, Scharringhausen T, de Boer A, Koopmanschap M. A comparative study of the role of disease severity in drug reimbursement decision making in four European countries. Health Policy. 2015;119(2):195–202. https://doi.org/10.1016/j.healthpol.2014.10.007Franken M, Stolk E, Scharringhausen T, de Boer A, Koopmanschap M. A comparative study of the role of disease severity in drug reimbursement decision making in four European countries. Health Policy. 2015;119(2):195–202. https://doi.org/10.1016/j.healthpol.2014.10.007Khunti K, Seidu S, Kunutsor S, Davies M. Association between adherence to pharmacotherapy and outcomes in type 2 diabetes: a meta-analysis. Diabetes Care. 2017;40(11):1588–96. https://doi.org/10.2337/dc16-1925Khunti K, Seidu S, Kunutsor S, Davies M. Association between adherence to pharmacotherapy and outcomes in type 2 diabetes: a meta-analysis. Diabetes Care. 2017;40(11):1588–96. https://doi.org/10.2337/dc16-1925van Boven JF, Chavannes NH, van der Molen T, Rutten-van Mölken MP, Postma MJ, Vegter S. Clinical and economic impact of non-adherence in COPD: a systematic review. Respir Med. 2014;108(1):103–13. https://doi.org/10.1016/j.rmed.2013.08.044van Boven JF, Chavannes NH, van der Molen T, Rutten-van Mölken MP, Postma MJ, Vegter S. Clinical and economic impact of non-adherence in COPD: a systematic review. Respir Med. 2014;108(1):103–13. https://doi.org/10.1016/j.rmed.2013.08.044Abegaz TM, Shehab A, Gebreyohannes EA, Bhagavathula AS, Elnour AA. Nonadherence to antihypertensive drugs: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(4):e5641. https://doi.org/10.1097/md.0000000000005641Abegaz TM, Shehab A, Gebreyohannes EA, Bhagavathula AS, Elnour AA. Nonadherence to antihypertensive drugs: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(4):e5641. https://doi.org/10.1097/md.0000000000005641Ruppar TM, Cooper PS, Mehr DR, Delgado JM, Dunbar-Jacob JM. Medication adherence interventions improve heart failure mortality and readmission rates: systematic review and meta-analysis of controlled trials. J Am Heart Assoc. 2016;5(6):e002606. https://doi.org/10.1161/jaha.115.002606Ruppar TM, Cooper PS, Mehr DR, Delgado JM, Dunbar-Jacob JM. Medication adherence interventions improve heart failure mortality and readmission rates: systematic review and meta-analysis of controlled trials. J Am Heart Assoc. 2016;5(6):e002606. https://doi.org/10.1161/jaha.115.002606Du L, Cheng Z, Zhang Y, Li Y, Mei D. The impact of medication adherence on clinical outcomes of coronary artery disease: a meta-analysis. Eur J Prev Cardiol. 2017;24(9):962–70. https://doi.org/10.1177/2047487317695628Du L, Cheng Z, Zhang Y, Li Y, Mei D. The impact of medication adherence on clinical outcomes of coronary artery disease: a meta-analysis. Eur J Prev Cardiol. 2017;24(9):962–70. https://doi.org/10.1177/2047487317695628Lai H, Li R, Li Z, Zhang B, Li C, Song C, et al. Modelling the impact of treatment adherence on the transmission of HIV drug resistance. J Antimicrob Chemother. 2023;78(8):1934–43. https://doi.org/10.1093/jac/dkad186Lai H, Li R, Li Z, Zhang B, Li C, Song C, et al. Modelling the impact of treatment adherence on the transmission of HIV drug resistance. J Antimicrob Chemother. 2023;78(8):1934–43. https://doi.org/10.1093/jac/dkad186Zozaya N, Alcalá B, Galindo J. The offset effect of pharmaceutical innovation: a review study. Glob Reg Health Technol Assess. 2019;2019(5):228424031987510. https://doi.org/10.1177/2284240319875108Zozaya N, Alcalá B, Galindo J. The offset effect of pharmaceutical innovation: a review study. Glob Reg Health Technol Assess. 2019;2019(5):228424031987510. https://doi.org/10.1177/2284240319875108Тихомирова АВ, Ягудина РИ. Фармакоэкономический анализ прямых медицинских затрат при лечении метастатического колоректального рака режимами XELOX или FOLFOX4 в сочетании с бевацизумабом или без него в качестве терапии первой линии. ФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология. 2010;3(2):22–7. EDN: MUDQUXTikhomirova АV, Yagudina RI. Pharmacoeconomic analysis of direct medical costs of metastatic colorectal cancer as the 1st line treatment regimes XELOX or FOLFOX and XELOX + BV OR FOLFOX + BV. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2010;3(2):22–7 (In Russ.). EDN: MUDQUXЯгудина РИ, Куликов АЮ, Комаров ИА. Анализ «затраты–эффективность» лечения пациентов, которым за последние 6 месяцев был поставлен диагноз хронический миелолейкоз в хронической фазе, лекарственными средствами группы ингибиторов тирозинкиназы–нилотиниба в сравнении с иматинибом. ФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология. 2013;6(2):42–7. EDN: RNKORXYagudina RI, Kulikov AYu, Komarov IA. Cost-effectiveness analysis over use of tyrosine kinase inhibitors (tasigna and gleevec) for treatment of chronic myeloid leukemia in the chronic phase as first-line therapy for de novo patients. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2013;6(2):42–7 (In Russ.). EDN: RNKORXКуликов АЮ, Нгуен T. Фармакоэкономический анализ одногодичной адъювантной терапии трастузумабом при НЕR2-положительном раке молочной железы ранней стадии. ФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология. 2010;3(4):28–34. EDN: NXZQIJKulikov AYu, Nguen T. Pharmacoeconomic analysis of 1-yearly adjuvant therapy of trastuzumab in early HER2-positive breast cancer. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2010;3(4):28–34 (In Russ.). EDN: NXZQIJСерпик ВГ. Фармакоэкономическая оценка терапии редких заболеваний на примере лечения первичного миелофиброза препаратом руксолитиниб. Фармакоэкономика: теория и практика. 2015;3(2):20–3. https://doi.org/10.30809/phe.2.2015.10Serpik V.G. Pharmacoeconomic evaluation of rare disease management in primary myelofibrosis treatment with ruxolitinib. Pharmacoeconomics: Theory and Practice. 2015;3(2):20–3 (In Russ.). https://doi.org/10.30809/phe.2.2015.10DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20–33. https://doi.org/10.1016/j.jhealeco.2016.01.012DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20–33. https://doi.org/10.1016/j.jhealeco.2016.01.012Schlander M, Hernandez-Villafuerte K, Cheng CY, Mestre-Fernandiz J, Baumann M. How much does it cost to research and develop a new drug? A systematic review and assessment. Pharmacoeconomics. 2021;39(11):1243–69. https://doi.org/10.1007/s40273-021-01065-ySchlander M, Hernandez-Villafuerte K, Cheng CY, MestreFernandiz J, Baumann M. How much does it cost to research and develop a new drug? A systematic review and assessment. Pharmacoeconomics. 2021;39(11):1243–69. https://doi.org/10.1007/s40273-021-01065-yMoon S, Mariat S, Kamae I, Pedersen HB. Defining the concept of fair pricing for medicines. BMJ. 2020;368:l4726 https://doi.org/10.1136/bmj.l4726Moon S, Mariat S, Kamae I, Pedersen HB. Defining the concept of fair pricing for medicines. BMJ. 2020;368:l4726 https://doi.org/10.1136/bmj.l4726Angelis A, Polyakov R, Wouters OJ, Torreele E, McKee M. High drug prices are not justified by industry’s spending on research and development. BMJ. 2023;380:e071710. https://doi.org/10.1136/bmj-2022-071710Angelis A, Polyakov R, Wouters OJ, Torreele E, McKee M. High drug prices are not justified by industry’s spending on research and development. BMJ. 2023;380:e071710. https://doi.org/10.1136/bmj-2022-071710Chan K, Sepassi A, Saunders IM, Goodman A, Watanabe JH. Effects of financial toxicity on prescription drug use and mental well-being in cancer patients. Explor Res Clin Soc Pharm. 2022;6:100136. https://doi.org/10.1016/j.rcsop.2022.100136Chan K, Sepassi A, Saunders IM, Goodman A, Watanabe JH. Effects of financial toxicity on prescription drug use and mental well-being in cancer patients. Explor Res Clin Soc Pharm. 2022;6:100136. https://doi.org/10.1016/j.rcsop.2022.100136Hussaini SMQ, Gupta A, Dusetzina SB. Financial toxicity of cancer treatment. JAMA Oncol. 2022;8(5):788. https://doi.org/10.1001/jamaoncol.2021.7987Hussaini SMQ, Gupta A, Dusetzina SB. Financial toxicity of cancer treatment. JAMA Oncol. 2022;8(5):788. https://doi.org/10.1001/jamaoncol.2021.7987Jung YL, Hwang J, Yoo HS. Disease burden metrics and the innovations of leading pharmaceutical companies: a global and regional comparative study. Global Health. 2020;16:80. https://doi.org/10.1186/s12992-020-00610-2Jung YL, Hwang J, Yoo HS. Disease burden metrics and the innovations of leading pharmaceutical companies: a global and regional comparative study. Global Health. 2020;16:80. https://doi.org/10.1186/s12992-020-00610-2The Lancet Respiratory Medicine. Where are the innovations in tuberculosis drug discovery? Lancet Respir Med. 2017;5(11):835. https://doi.org/10.1016/S2213-2600(17)30376-4The Lancet Respiratory Medicine. Where are the innovations in tuberculosis drug discovery? Lancet Respir Med. 2017;5(11):835. https://doi.org/10.1016/S2213-2600(17)30376-4Abdelsayed M, Kort EJ, Jovinge S, Mercola M. Repurposing drugs to treat cardiovascular disease in the era of precision medicine. Nat Rev Cardiol. 2022;19(11):751–64. https://doi.org/10.1038/s41569-022-00717-6Abdelsayed M, Kort EJ, Jovinge S, Mercola M. Repurposing drugs to treat cardiovascular disease in the era of precision medicine. Nat Rev Cardiol. 2022;19(11):751–64. https://doi.org/10.1038/s41569-022-00717-6Van Norman GA. Overcoming the declining trends in innovation and investment in cardiovascular therapeutics: beyond EROOM’s law. JACC Basic Transl Sci. 2017;2(5):613–25. https://doi.org/10.1016/j.jacbts.2017.09.002Van Norman GA. Overcoming the declining trends in innovation and investment in cardiovascular therapeutics: beyond EROOM’s law. JACC Basic Transl Sci. 2017;2(5):613–25. https://doi.org/10.1016/j.jacbts.2017.09.002Klug DM, Idiris FIM, Blaskovich MAT, von Delft F, Dowson CG, Kirchhelle C, et al. There is no market for new antibiotics: this allows an open approach to research and development. Wellcome Open Res. 2021;6:146. https://doi.org/10.12688/wellcomeopenres.16847.1Klug DM, Idiris FIM, Blaskovich MAT, von Delft F, Dowson CG, Kirchhelle C, et al. There is no market for new antibiotics: this allows an open approach to research and development. Wellcome Open Res. 2021;6:146. https://doi.org/10.12688/wellcomeopenres.16847.1Miller KL, Fermaglich LJ, Maynard J. Using four decades of FDA orphan drug designations to describe trends in rare disease drug development: substantial growth seen in development of drugs for rare oncologic, neurologic, and pediatric-onset diseases. Orphanet J Rare Dis. 2021;16(1):265. https://doi.org/10.1186/s13023-021-01901-6Miller KL, Fermaglich LJ, Maynard J. Using four decades of FDA orphan drug designations to describe trends in rare disease drug development: substantial growth seen in development of drugs for rare oncologic, neurologic, and pediatric-onset diseases. Orphanet J Rare Dis. 2021;16(1):265. https://doi.org/10.1186/s13023-021-01901-6Wellman-Labadie O, Zhou Y. The US Orphan Drug Act: rare disease research stimulator or commercial opportunity? Health Policy. 2010;95(2–3):216–28. https://doi.org/10.1016/j.healthpol.2009.12.001Wellman-Labadie O, Zhou Y. The US Orphan Drug Act: rare disease research stimulator or commercial opportunity? Health Policy. 2010;95(2–3):216–28. https://doi.org/10.1016/j.healthpol.2009.12.001Årdal C, Lacotte Y, Ploy MC. Financing pull mechanisms for antibiotic-related innovation: opportunities for Europe. Clin Infect Dis. 2020;71(8):1994–9. https://doi.org/10.1093/cid/ciaa153Årdal C, Lacotte Y, Ploy MC. Financing pull mechanisms for antibiotic-related innovation: opportunities for Europe. Clin Infect Dis. 2020;71(8):1994–9. https://doi.org/10.1093/cid/ciaa153Проценко МВ, Серпик ВГ. Обзор международной классификации редких заболеваний. Фармакоэкономика: теория и практика. 2021;9(2):18–20. https://doi.org/10.30809/phe.2.2021.3Protsenko MV, Serpik VG. Review of the international classification of rare diseases. Pharmacoeconomics: Theory and Practice. 2021;9(2):18–20 (In Russ). https://doi.org/10.30809/phe.2.2021.3Ding C, Wu Y, Chen X, Chen Y, Wu Z, Lin Z, et al. Global, regional, and national burden and attributable risk factors of neurological disorders: the Global Burden of Disease study 1990–2019. Front Public Health. 2022;10:952161. https://doi.org/10.3389/fpubh.2022.952161Ding C, Wu Y, Chen X, Chen Y, Wu Z, Lin Z, et al. Global, regional, and national burden and attributable risk factors of neurological disorders: the Global Burden of Disease study 1990–2019. Front Public Health. 2022;10:952161. https://doi.org/10.3389/fpubh.2022.952161Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer’s disease drug development pipeline: 2023. Alzheimers Dement (NY). 2023;9(2):e12385. Erratum: Alzheimers Dement (NY). 2023;9(2):e12407. https://doi.org/10.1002/trc2.12385Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer’s disease drug development pipeline: 2023. Alzheimers Dement (NY). 2023;9(2):e12385. Erratum: Alzheimers Dement (NY). 2023;9(2):e12407. https://doi.org/10.1002/trc2.12385Бачурин СО. Препараты для лечения болезни Альцгеймера по данным клинических испытаний и основные тенденции в подходах к поиску новых лекарственных средств. Журнал неврологии и психиатрии им. С.С. Корсакова. 2016;116(8):77–87. https://doi.org/10.17116/jnevro20161168177-87Bachurin SO. A review of drugs for treatment of Alzheimer’s disease in clinical trials: main trends. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(8):77–87 (In Russ.). https://doi.org/10.17116/jnevro20161168177-87Rabaneda-Bueno R, Mena-Montes B, Torres-Castro S, Torres-Carrillo N, Torres-Carrillo NM. Advances in genetics and epigenetic alterations in Alzheimer’s disease: a notion for therapeutic treatment. Genes (Basel). 2021;12(12):1959. https://doi.org/10.3390/genes12121959Rabaneda-Bueno R, Mena-Montes B, Torres-Castro S, Torres-Carrillo N, Torres-Carrillo NM. Advances in genetics and epigenetic alterations in Alzheimer’s disease: a notion for therapeutic treatment. Genes (Basel). 2021;12(12):1959. https://doi.org/10.3390/genes12121959Sasso JM, Ambrose BJB, Tenchov R, Datta RS, Basel MT, DeLong RK, Zhou QA. The progress and promise of RNA medicine — an arsenal of targeted treatments. J Med Chem. 2022;65(10):6975–7015. https://doi.org/10.1021/acs.jmedchem.2c00024Sasso JM, Ambrose BJB, Tenchov R, Datta RS, Basel MT, DeLong RK, Zhou QA. The progress and promise of RNA medicine — an arsenal of targeted treatments. J Med Chem. 2022;65(10):6975–7015. https://doi.org/10.1021/acs.jmedchem.2c00024Yu AM, Choi YH, Tu MJ. RNA drugs and RNA targets for small molecules: principles, progress, and challenges. Pharmacol Rev. 2020;72(4):862–98. https://doi.org/10.1124/pr.120.019554Yu AM, Choi YH, Tu MJ. RNA drugs and RNA targets for small molecules: principles, progress, and challenges. Pharmacol Rev. 2020;72(4):862–98. https://doi.org/10.1124/pr.120.019554Boada C, Sukhovershin R, Pettigrew R, Cooke JP. RNA therapeutics for cardiovascular disease. Curr Opin Cardiol. 2021;36(3):256–63. https://doi.org/10.1097/hco.0000000000000850Boada C, Sukhovershin R, Pettigrew R, Cooke JP. RNA therapeutics for cardiovascular disease. Curr Opin Cardiol. 2021;36(3):256–63. https://doi.org/10.1097/hco.0000000000000850Biernacki MA, Brault M, Bleakley M. T-cell receptor-based immunotherapy for hematologic malignancies. Cancer J. 2019;25(3):179–90. https://doi.org/10.1097/ppo.0000000000000378Biernacki MA, Brault M, Bleakley M. T-cell receptor-based immunotherapy for hematologic malignancies. Cancer J. 2019;25(3):179–90. https://doi.org/10.1097/ppo.0000000000000378Helsen CW, Hammill JA, Lau VWC, Mwawasi KA, Afsahi A, Bezverbnaya K, et al. The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity. Nat Commun. 2018;9(1):3049. https://doi.org/10.1038/s41467-018-05395-yHelsen CW, Hammill JA, Lau VWC, Mwawasi KA, Afsahi A, Bezverbnaya K, et al. The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity. Nat Commun. 2018;9(1):3049. https://doi.org/10.1038/s41467-018-05395-yChen Y, Yu Z, Tan X, Jiang H, Xu Z, Fang Y, et al. CAR-macrophage: a new immunotherapy candidate against solid tumors. Biomed Pharmacother. 2021;139:111605. https://doi.org/10.1016/j.biopha.2021.111605Chen Y, Yu Z, Tan X, Jiang H, Xu Z, Fang Y, et al. CAR-macrophage: a new immunotherapy candidate against solid tumors. Biomed Pharmacother. 2021;139:111605. https://doi.org/10.1016/j.biopha.2021.111605Wrona E, Borowiec M, Potemski P. CAR-NK cells in the treatment of solid tumors. Int J Mol Sci. 2021;22(11):5899. https://doi.org/10.3390/ijms22115899Wrona E, Borowiec M, Potemski P. CAR-NK cells in the treatment of solid tumors. Int J Mol Sci. 2021;22(11):5899. https://doi.org/10.3390/ijms22115899

The authors declare that there are no conflicts of interest present.