Consensus on implementation features of the Russian-manufactured generic Nusinersen (TN Lantesens) for SMA 5q treatment in Russia

В настоящее время в России для лечения пациентов со спинальной мышечной атрофией (СМА) зарегистрированы, включены в клинические рекомендации и применяются в клинической практике препараты патогенетической и генозаместительной терапии [1–5]. Препараты патогенетической терапии увеличивают продукцию белка SMN за счёт модификации сплайсинга гена SMN2 и применяются пожизненно. К ним относятся нусинерсен [2, 3] — антисмысловой олигонуклеотид, вводимый интратекально, и рисдиплам [4], относящийся к малым молекулам, применяемый перорально. Препарат генозаместительной терапии онасемноген абепарвовек [5] замещает функции дефектного гена SMN1 его функциональной копией, восстанавливая продукцию белка SMN, и применяется однократно внутривенно. Появление и применение этих препаратов в лечении СМА значительно улучшило выживаемость и прогноз пациентов [6].

1. Proximal spinal muscular atrophy 5q, children. Clinical Guidelines; 2023 Available at: https://cr.minzdrav.gov.ru/schema/780_1 (in Russian)

2. General characteristics of the medicinal product Spinraza LP-No.(005833)-(RG-RU); 2024. Available at: https://lk.regmed.ru/Register/EAEU_SmPC (in Russian)

3. General characteristics of the medicinal product Alantesens LP-No.(005199)-(RG-RU); 2024. Available at: https://lk.regmed.ru/Register/EAEU_SmPC (in Russian)

4. General characteristics of the medicinal product Avrisdi LP-No.(008925)-(RG-RU); 2025. Available at: https://lk.regmed.ru/Register/EAEU_SmPC (in Russian)

5. General characteristics of the medicinal product Zolgensma LP-No.(001462)-(RG-RU); 2022. Available at: https://lk.regmed.ru/Register/EAEU_SmPC (in Russian)

6. The path from theory to practice in the diagnosis and treatment of patients with spinal muscular atrophy. Russkii zhurnal detskoi nevrologii. 2024; 19(2): 80–8. https://doi.org/10.17650/2073-8803-2024-19-2-80-88 (in Russian)

7. Decree of the Government of the Russian Federation No. 1495-r «On the Development Strategy of the pharmaceutical industry of the Russian Federation for the period up to 2030»; 2023. (in Russian)

8. Federal Law on the Circulation of Medicines No. 61; 2010. (in Russian)

9. Decision of the Council of the Eurasian Economic Commission No. 78 «On the Rules for Registration and examination of medicines for medical use»; 2016. (in Russian)

10. Decision of the Council of the Eurasian Economic Commission No. 85 «On approval of the Rules for conducting Bioequivalence studies of medicines within the framework of the Eurasian Economic Union»; 2016. (in Russian)

11. Expert report of the Federal State Budgetary Institution «Scientific Center for Expertise of Medical Devices» of the Ministry of Health of the Russian Federation on the assessment of safety, efficacy and quality of the medicinal product Lantesens®. Own data of JSC Generium. (in Russian)

12. According to art. 27.1 of Federal Law No. 61 and the published list of interchangeable drugs on the website of the State Register of Medicines. Available at: http://grls.rosminzdrav.ru/Forum//Files/243339/%D0%9F%D0%B5%D1%80%D0%B5%D1%87%D0%B5%D0%BD%D1%8C_(%D0%BC%D0%B0%D1%80%D1%82_2025).xls (in Russian)

13. Biogen’s press release. Available at: https://investors.biogen.com/news-releases/news-release-details/us-fda-approves-biogens-spinrazatm-nusinersen-first-treatment (in Russian)

14. Highlights of prescribing information: Spinraza (nusinersen) injection, for intrathecal use. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209531lbl.pdf

15. EMEA. Spinraza®. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/spinraza

16. The list for purchases on the website of the Circle of Goodness Foundation. Available at: https://фондкругдобра.рф/ (in Russian)

17. Artemieva S.B., Kuzenkova L.M., Ilyina E.S., Kursakova Yu.A., Kolpakchi L.M., Sapego E.Yu., et al. The efficacy and safety of Nusinersen within the expanded access program in Russia. Nervno-myshechnye bolezni. 2020; 10(3): 35–41. https://doi.org/10.17650/2222-8721-2020-10-3-35-41 https://elibrary.ru/ouhjuq (in Russian)

18. Consensus on gene replacement therapy for the treatment for spinal muscular atrophy (Release № 2). Nevrologicheskii zhurnal imeni L.O. Badalyana. 2023; 4(2): 64–73. https://doi.org/10.46563/2686-8997-2023-4-2-64-73 https://elibrary.ru/cgpzyn (in Russian)

19. Glanzman A.M., Mazzone E., Main M., Pelliccioni M., Wood J., Swoboda K.J., et al. The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability. Neuromuscul. Disord. 2010; 20(3): 155–61. https://doi.org/10.1016/j.nmd.2009.11.014

20. MFM. Available at: https://mfm-nmd.org/learn-more-about-mfm/?lang=en

21. Mazzone E., De Sanctis R., Fanelli L., Bianco F., Main M., van den Hauwe M., et al. Hammersmith Functional Motor Scale and Motor Function Measure-20 in non ambulant SMA patients. Neuromuscul. Disord. 2014; 24(4): 347–52. https://doi.org/10.1016/j.nmd.2014.01.003

22. Mazzone E.S., Mayhew A., Montes J., Ramsey D., Fanelli L., Young S.D., et al. Revised upper limb module for spinal muscular atrophy: Development of a new module. Muscle Nerve. 2017; 55(6): 869–74. https://doi.org/10.1002/mus.25430

23. Montes J., McDermott M.P., Martens W.B., Dunaway S., Glanzman A.M., Riley S., et al. Six-Minute Walk Test demonstrates motor fatigue in spinal muscular atrophy. Neurology. 2010; 74(10): 833–8. https://doi.org/10.1212/wnl.0b013e3181d3e308

24. The data was provided by Generium JSC based on reports of adverse events in the Roszdravnadzor AIS database. The company’s own data. (in Russian)

25. The NURTURE Study. A clinical study in newborn babies with a genetic diagnosis of Spinal Muscular Atrophy (SMA); 2020. Available at: https://assets.sma-europe.eu/Nurture_Study_Brochure_29_09_21_465aeec3d8.pdf

26. Finkel R.S., Mercuri E., Darras B.T., Connolly A.M., Kuntz N.L., Kirschner J., et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N. Engl. J. Med. 2017; 377(18): 1723–32. https://doi.org/10.1056/nejmoa1702752

27. Castro D., Finkel R.S., Farrar M.A., Tulinius M., Krosschell K.J., Saito K., et al. Nusinersen in infantile-onset spinal muscular atrophy: results from longer-term treatment from the open-label SHINE extension study. Neurology. 2020; 94(15 Suppl.): 1640. https://doi.org/10.1212/WNL.94.15_supplement.1640

28. Mercuri E., Darras B.T., Chiriboga C.A., Day J.W., Campbell C., Connolly A.M., et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N. Engl. J. Med. 2018; 378(7): 625–35. https://doi.org/10.1056/nejmoa1710504

29. Chirboga C.A., Darras B.T., Farrara M.A., Mercuri E., Kirschner J., Kuntz N.L., et al. Longer-term treatment with Nusinersen: results in later-onset spinal muscular atrophy from the SHINE study. Neurology. 2020; 94(15 Suppl.): 166. https://doi.org/10.1212/WNL.94.15_supplement.1661