Strategic Indicators in the Development of Original Medicinal Products in 2024: Analysis of Pipelines of International Pharmaceutical Leaders

INTRODUCTION. Major international pharmaceutical companies play a crucial role in the development of original medicines. To determine the directions for original medicines development in Russia, it is essential to analyze global trends and emerging weak signals (tendencies) — early indicators of future-significant innovations.

OBJECTIVE. To identify trends and emerging weak signals that could shape pharmaceutical development in Russia through an analysis of the pipeline of original medicines being developed by global pharma leaders.

MATERIALS AND METHODS. An analysis was conducted on the medicinal product development plans for 2024 of the 20 largest pharmaceutical companies globally, which have the highest research and development budgets. The focus was on original medicines scheduled for clinical trials Phase 1 from January to May 2024. A descriptive research approach was applied, based on retrospective analysis of secondary data. The study measured the number of original medicines under development, research directions, target classes, medicine types, and groups. Both quantitative and qualitative evaluations were used to identify key trends and tendencies (emerging weak signals) in pharmaceutical development of medicines.

RESULTS. During the analyzed period, 17 out of 20 leading pharmaceutical companies-initiated Phase 1 trials for a total of 84 original medicines. The most active research areas included oncology, endocrinology and metabolism, cardiovascular system, and immunology. Notably, 40 medicines entered Phase 1 trials in oncology. The largest share (42%) of the medicines in development consists of high molecular weight molecules. Based on the number of medicines developed by multiple companies, trends were identified for the following medicine classes: “Large molecule” — bispecific antibodies (10 medicines, 5 developers); monospecific antibodies (8 medicines, 7 developers); antibody-drug conjugates (8 medicines, 3 developers); “Small molecule” — enzyme inhibitors (9 medicines, 6 developers); “Cell therapy” — CAR-T-based therapies (6 medicinal products, 2 developers).

CONCLUSIONS. Current trends in targeted therapy development include the creation of bispecific antibodies and next-generation antibody-drug conjugates, alongside CAR-T therapies based on autologous T cells, predominantly for the treatment of malignant neoplasms. The study of multispecific antibodies is shaping a new direction in targeted cancer therapy. The development of low-molecular-weight enzyme inhibitors is establishing a trend in various therapeutic areas. Specifically, enzyme inhibitors targeting synthetic lethal vulnerabilities like WRN and PRMT5 are emerging as a key tendency in small-molecule medicine development for targeted cancer therapy.

1. Schuhmacher A, Gassmann O, Hinder M, Hartl D. Comparative analysis of FDA approvals by top 20 pharma companies (2014-2023). Drug Discov Today. 2024;29(9):104128. https://doi.org/10.1016/j.drudis.2024.104128

2. Yao Y, Hu Y, Wang F. Trispecific antibodies for cancer immunotherapy. Immunology. 2023;169(4):389–99. https://doi.org/10.1111/imm.13636

3. Tapia-Galisteo A, Compte M, Álvarez-Vallina L, Sanz L. When three is not a crowd: Trispecific antibodies for enhanced cancer immunotherapy. Theranostics. 2023;13(3):1028–41. https://doi.org/10.7150/thno.81494

4. Mullard A. Trispecific antibodies take to the clinic. Nat Rev Drug Discov. 2020;19(10):657–8. https://doi.org/10.1038/d41573-020-00164-3

5. Shim H. Bispecific antibodies and antibody-drug conjugates for cancer therapy: technological considerations. Biomolecules. 2020;10(3):360. https://doi.org/10.3390/biom10030360

6. Lu RM, Hwang YC, Liu IJ, Lee CC, Tsai HZ, Li HJ, Wu HC. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci. 2020;27(1):1. https://doi.org/10.1186/s12929-019-0592-z

7. Lu J, Ding J, Liu Z, Chen T. Retrospective analysis of the preparation and application of immunotherapy in cancer treatment (Review). Int J Oncol. 2022;60(2):12. https://doi.org/10.3892/ijo.2022.5302

8. Pineda C, Illades-Aguiar B, Flores-Alfaro E, Leyva-Vázquez MA, Parra-Rojas I, Del Moral-Hernández O, et al. Mechanisms of action and limitations of monoclonal antibodies and single chain fragment variable (scFv) in the treatment of cancer. Biomedicines. 2023;11(6):1610. https://doi.org/10.3390/biomedicines11061610

9. Ruan DY, Wu HX, Meng Q, Xu RH. Development of antibody-drug conjugates in cancer: Overview and prospects. Cancer Commun (Lond). 2024;44(1):3–22. https://doi.org/10.1002/cac2.12517

10. Stepanova EO, Moiseenko FV, Moiseyenko VM. Antubody-drug conjugates. Practical Oncology. 2023;24(1):7–18 (In Russ.). https://doi.org/10.31917/2401007

11. Vasilevich NI, Chestkov AV, Yang M, Sun L. Chimeric conjugants based on proteins and peptides in targeted anticancer therapy. Laboratory and Manufacturing. 2023;23(1):56–64 (In Russ.). https://doi.org/10.32757/2619-0923.2023.1.23.56.64

12. Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the «biological missile» for targeted cancer therapy. Signal Transduct Target Ther. 2022;7(1):93. https://doi.org/2010.1038/s41392-022-00947-7

13. Ma Y, Huang Y, Zhao Y, Zhao S, Xue J, Yang Y, et al. BL-B01D1, a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study. Lancet Oncol. 2024;25(7):901–11. https://doi.org/10.1016/S1470-2045(24)00159-1

14. Solopova ON, Misyurin VA. Bispecific antibodies in clinical practice and clinical trials (literature review). Clinical Oncohematology. 2019;12(2):125–44 (In Russ). https://doi.org/2010.21320/2500-2139-2019-12-2-125-144

15. Kuchnio A, Samakai E, Hug E, Balmaña M, Janssen L, Amorim R, et al. Discovery of JNJ-88549968, a novel, first-in-class CALRmutxCD3 T-cell redirecting antibody for the treatment of myeloproliferative neoplasms. Blood. 2023;142(1):1777. https://doi.org/10.1182/blood-2023-173430

16. Saura-Esteller J, de Jong M, King L, Ensing E, Winograd B, de Gruijl T, et al. Gamma delta T-cell based cancer immunotherapy: Past — present — future. Front Immunol. 2022;13:915837. https://doi.org/10.3389/fimmu.2022.915837

17. Scaletta L, Kuriakose T, Nanda S, Collins M, Darrah E, McInnes I, et al. Blockade of soluble and cell surface PAD activity prevents the generation of citrullinated autoantigens recognized by RA patients’ serum [abstract]. Arthritis Rheumatol. 2024;76(9).

18. Keri D, Walker M, Singh I, Nishikawa K, Garces F. Next generation of multispecific antibody engineering. Antib Ther. 2023;7(1):37–52. https://doi.org/10.1093/abt/tbad027

19. Amash A, Volkers G, Farber P, Griffin D, Davison K, Goodman A, et al. Developability considerations for bispecific and multispecific antibodies. mAbs. 2024;6(1):2394229. https://doi.org/10.1080/19420862.2024.2394229

20. Stone J, Pear Fish K, Ashok D, McKay L. Abstract ND01: ABBV-303: A novel NK and CD8 T cell engager specific for c-Met-expressing tumors. Cancer Research. 2024;84(7_Supplement):ND01. https://doi.org/10.1136/jitc-2024-SITC2024.1282

21. Motolani A, Martin M, Sun M, Lu T. The structure and functions of PRMT5 in human diseases. Life (Basel). 2021;11(10):1074. https://doi.org/10.3390/life11101074

22. Kalev P, Hyer ML, Gross S, Konteatis Z, Chen CC, Fletcher M, et al. MAT2A inhibition blocks the growth of MTAP-deleted cancer cells by reducing PRMT5-dependent mRNA splicing and inducing DNA damage. Cancer Cell. 2021;39(2):209-24. e11. https://doi.org/10.1016/j.ccell.2020.12.010

23. Ikushima H, Watanabe K, Shinozaki-Ushiku A, Oda K, Kage H. Pan-cancer clinical and molecular landscape of MTAP deletion in nationwide and international comprehensive genomic data. ESMO Open. 2025;10(4):104535. https://doi.org/10.1016/j.esmoop.2025.104535

24. Engstrom L, Aranda R, Waters L, Moya K, Bowcut V, Vegar L, et al. MRTX1719 is an MTA-cooperative PRMT5 inhibitor that exhibits synthetic lethality in preclinical models and patients with MTAP-deleted cancer. Cancer Discov. 2023;13(11):2412–31. https://doi.org/10.1158/2159-8290.CD-23-0669

25. Chan E, Shibue T, McFarland J, Gaeta B, Ghandi M, Dumont N, et al. WRN helicase is a synthetic lethal target in microsatellite unstable cancers. Nature. 2019;568(7753):551–6. https://doi.org/10.1038/s41586-019-1102-x

26. Wainberg ZA. WRN helicase: Is there more to MSI-H than immunotherapy? Cancer Discov. 2024;14(8):1369–71. https://doi.org/10.1158/2159-8290.CD-24-0771

27. Mengoli V, Ceppi I, Sanchez A, Cannavo E, Halder S, Scaglione S, et al. WRN helicase and mismatch repair complexes independently and synergistically disrupt cruciform DNA structures. EMBO J. 2023;42(3):e111998. https://doi.org/10.15252/embj.2022111998

28. Morales-Juarez D., Jackson S. Clinical prospects of WRN inhibition as a treatment for MSI tumours. NPJ Precis Oncol. 2022;6(1):85. https://doi.org/10.1038/s41698-022-00319-y

29. Zhou D, Liu T, Rao X, Jie X, Chen Y, Wu Z, et al. Targeting diacylglycerol kinase α impairs lung tumorigenesis by inhibiting cyclin D3. Thorac Cancer. 2023;14(13):1179–91. https://doi.org/10.1111/1759-7714.14851

30. Fu L, Li S, Xiao W, Yu K, Li S, Yuan S, et al. DGKA mediates resistance to PD-1 blockade. Cancer Immunol Res. 2021;9(4):371–85. https://doi.org/10.1158/2326-6066.cir-20-0216

31. Sabnis R. Novel CDK2 inhibitors for treating cancer. ACS Med Chem Lett. 2020;11(12):2346–7. https://doi.org/10.1021/acsmedchemlett.0c00500

32. Jensen L, Attfield K, Feldmann M, Fugger L. Allosteric TYK2 inhibition: Redefining autoimmune disease therapy beyond JAK1-3 inhibitors. EBioMedicine. 2023;97:104840. https://doi.org/10.1016/j.ebiom.2023.104840

33. Nogueira M, Puig L, Torres T. JAK inhibitors for treatment of psoriasis: Focus on selective TYK2 inhibitors. Drugs. 2020; 80(4):341–52. https://doi.org/10.1007/s40265-020-01261-8

34. Armstrong A, Gooderham M, Warren R, Papp K, Strober B, Thaçi D, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol. 2023;88(1):29–39. https://doi.org/10.1016/j.jaad.2022.07.002

35. Jagannath A, Taylor L, Ru Y, Wakaf Z, Akpobaro K, Vasudevan S, et al. The multiple roles of salt-inducible kinases in regulating physiology. Physiol Rev. 2023;103(3):2231–69. https://doi.org/10.1016/j.jaad.2022.07.002

36. Melnikova EV, Merkulov VA, Merkulova OV. Regulation for the translation of gene and cell therapy into medical practice in East Asian countries. 2024;14(1):29–41 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-1-29-41

37. Vodyakova MA, Pokrovsky NS, Semenova IS, Merkulov VA, Melnikova EV. Classification of cell therapy products by cell manipulation degree and functions performed: Analysis of international regulatory approaches. Regulatory Research and Medicine Evaluation. 2024;14(5):533–46 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-1-29-41

38. Uscanga-Palomeque AC, Chávez-Escamilla AK, Alvizo-Báez CA, Saavedra-Alonso S, Terrazas-Armendáriz LD, Tamez-Guerra RS, et al. CAR-T cell therapy: From the shop to cancer therapy. Int J Mol Sci. 2023;24(21):15688. https://doi.org/10.3390/ijms242115688

39. Jones LA, Conway GE, Nguyen-Chi A, Burnell S, Jenkins GJ, Conlan RS, Doak SH. Investigating STEAP2 as a potential therapeutic target for the treatment of aggressive prostate cancer. Cell Mol Biol (Noisy-le-grand). 2023;69(4):179–87. https://doi.org/10.14715/cmb/2023.69.4.28

40. Zanvit P, van Dyk D, Fazenbaker C, McGlinchey K, Luo W, Pezold J, et al. Antitumor activity of AZD0754, a dnT-GFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer. J Clin Invest. 2023;133(22):e169655. https://doi.org/10.1172/JCI169655