瑞士巴塞爾2025年12月10日 /美通社/ -- 諾華近日宣布VAYHIT2三期臨床試驗(yàn)取得積極結(jié)果，該試驗(yàn)評估了ianalumab聯(lián)合艾曲泊帕在既往接受糖皮質(zhì)激素治療的原發(fā)性免疫性血小板減少癥（ITP）患者中的療效和安全性[1-3]。Ianalumab（9 mg/kg）聯(lián)合艾曲泊帕將ITP疾病控制延長了45%，該結(jié)果基于主要研究終點(diǎn)"至治療失敗時(shí)間（TTF, Time To Treatment Failure）"，即評估患者在治療期間及治療后維持安全血小板水平的時(shí)間[1,2]。接受ianalumab聯(lián)合艾曲泊帕治療的患者，其至治療失敗的中位時(shí)間是安慰劑聯(lián)合艾曲泊帕組的2.8倍（13.0個(gè)月 vs 4.7個(gè)月）[1,2]。
詳細(xì)數(shù)據(jù)于第67屆美國血液學(xué)會(huì)年會(huì)（ASH）的最新突破摘要（Late-Breaking Abstracts） 專場公布，并同步發(fā)表于《新英格蘭醫(yī)學(xué)雜志》[1,2]。
"ITP的治療一直以來側(cè)重于提升血小板計(jì)數(shù)，通常需要長期治療以控制疾病。這意味著許多患者需要長期用藥，持續(xù)承受疾病負(fù)擔(dān)和如疲勞等的癥狀，"麻總百瀚醫(yī)院（Mass General Brigham）血液學(xué)/腫瘤學(xué) Peggy S. Blitz 講席教授、哈佛醫(yī)學(xué)院醫(yī)學(xué)副教授Hanny Al-Samkari博士表示，"VAYHIT2試驗(yàn)結(jié)果令人鼓舞，顯示即使在患者停藥期間也能實(shí)現(xiàn)更好的疾病控制，為ITP患者帶來新的希望。"
接受ianalumab（9 mg/kg）聯(lián)合艾曲泊帕治療的患者，在第6個(gè)月時(shí)持續(xù)血小板計(jì)數(shù)改善的比例也顯著高于安慰劑聯(lián)合艾曲泊帕治療組（62% vs 39%），達(dá)到了關(guān)鍵次要終點(diǎn)[1,2]。疲勞改善方面，PROMIS疲勞評分顯示，ianalumab聯(lián)合艾曲泊帕組平均下降7.7分，安慰劑聯(lián)合艾曲泊帕治療組下降3.6分[1,2]。
"B細(xì)胞驅(qū)動(dòng)的自身免疫反應(yīng)導(dǎo)致ITP患者血小板破壞和出血風(fēng)險(xiǎn)增加。Ianalumab的創(chuàng)新雙重作用機(jī)制旨在清除B細(xì)胞并阻斷其存活信號。"諾華全球腫瘤開發(fā)負(fù)責(zé)人Mark Rutstein博士表示，"憑借我們在ITP領(lǐng)域多年的經(jīng)驗(yàn)，VAYHIT2結(jié)果進(jìn)一步證明ianalumab有望通過每月一次、共四次的靜脈輸注方案，實(shí)現(xiàn)持久疾病控制，讓患者無需長期持續(xù)治療。"
VAYHIT2評估了兩種劑量的ianalumab，其中9 mg/kg劑量在主要和關(guān)鍵次要終點(diǎn)均顯示出統(tǒng)計(jì)學(xué)顯著改善，3 mg/kg劑量在主要終點(diǎn)達(dá)到統(tǒng)計(jì)學(xué)顯著，關(guān)鍵次要終點(diǎn)有數(shù)值改善[1-3]。
Ianalumab 9 mg/kg + 艾曲泊帕 (N=50) |
Ianalumab 3 mg/kg + 艾曲泊帕 (N=51) |
安慰劑 + 艾曲泊帕 (N=51) |
|
主要終點(diǎn)： 至治療失敗時(shí)間（TTF） |
13.0個(gè)月 (HR 0.55; 95% CI: 0.32, 0.92; p=0.021a) |
尚無法估算 (HR 0.58; 95% CI: 0.34, 0.98; p=0.023a) |
4.7個(gè)月 |
關(guān)鍵次要終點(diǎn)： 6個(gè)月時(shí)持續(xù)應(yīng)答率（SR6） |
62.0% (p=0.023a) |
56.9% (p=0.035a) |
39.2 %
|
a. 統(tǒng)計(jì)學(xué)顯著性所需p值為單側(cè)<0.025
Ianalumab耐受性良好，未發(fā)現(xiàn)新的安全信號，安全性與既往研究一致[1,2]。Ianalumab組與安慰劑組的不良事件發(fā)生率相當(dāng)，最常見的不良事件為頭痛（9 mg/kg組14%，3 mg/kg組10%，安慰劑組8%）和輸注相關(guān)反應(yīng)（9 mg/kg組14%，3 mg/kg組8%，安慰劑組8%）[1,2]。中性粒細(xì)胞減少癥*在ianalumab組更常見（9 mg/kg組16%，3 mg/kg組12%，安慰劑組2%），大多數(shù)病例無需治療或劑量調(diào)整即可恢復(fù)[1,2]。未有因治療期間不良事件導(dǎo)致永久停藥的情況[1,2]。
VAYHIT2是ianalumab的第三項(xiàng)獲得陽性結(jié)果的III期臨床試驗(yàn)，此前在活動(dòng)性干燥綜合征成人患者中已有兩項(xiàng)陽性結(jié)果[1,4]。諾華計(jì)劃于2027年將VAYHIT2數(shù)據(jù)與正在進(jìn)行的一線ITP試驗(yàn)結(jié)果（VAYHIT1）一同提交。Ianalumab已獲得美國食品藥品監(jiān)督管理局（FDA）和歐洲藥品管理局（EMA）的孤兒藥資格認(rèn)定[5,6]。
*注：中性粒細(xì)胞減少癥為特別關(guān)注不良事件，包括多種與中性粒細(xì)胞、中性粒前體細(xì)胞及白細(xì)胞減少相關(guān)的術(shù)語。 |
關(guān)于ianalumab
Ianalumab（VAY736）是一種新型全人源單克隆抗體，正在開發(fā)用于治療多種B細(xì)胞介導(dǎo)的自身免疫性疾病，包括干燥綜合征、免疫性血小板減少癥（ITP）、系統(tǒng)性紅斑狼瘡（SLE）、狼瘡性腎炎（LN）、溫抗體型自身免疫性溶血性貧血（wAIHA）及彌漫性皮膚系統(tǒng)性硬化癥（dcSSc）[3,7-13]。其作用機(jī)制通過兩種途徑靶向B細(xì)胞：一方面通過抗體依賴性細(xì)胞毒作用（ADCC）耗竭B細(xì)胞，另一方面，阻斷BAFF-R介導(dǎo)的B細(xì)胞功能及存活信號[8]。臨床試驗(yàn)顯示，ianalumab在干燥綜合征、系統(tǒng)性紅斑狼瘡和免疫性血小板減少癥中具有良好的療效和安全性[4,14-16]。Ianalumab最初由MorphoSys AG公司與諾華早期合作開發(fā)，諾華于2024年收購了該公司[17]。
關(guān)于原發(fā)性免疫性血小板減少癥
原發(fā)性免疫性血小板減少癥（ITP）是一種罕見的自身免疫性疾病，患者的免疫系統(tǒng)錯(cuò)誤地攻擊并破壞血小板——血液凝固所必需的細(xì)胞[18]。這會(huì)導(dǎo)致出血時(shí)間延長、易瘀傷和慢性疲勞等癥狀，嚴(yán)重影響日常生活[18,19]。
盡管已有多種治療方法，許多ITP患者仍需多次更換治療方案，難以實(shí)現(xiàn)長期疾病控制[20]。現(xiàn)有治療多以維持安全血小板水平和預(yù)防出血為主，往往需要長期用藥[20,21]。長期治療負(fù)擔(dān)和復(fù)發(fā)的不確定性嚴(yán)重影響患者生活質(zhì)量[19,22]。亟需能夠?qū)崿F(xiàn)持久反應(yīng)、減少長期治療負(fù)擔(dān)的新療法[23]。
關(guān)于VAYHIT2
VAYHIT2（NCT05653219）是一項(xiàng)III期、多中心、隨機(jī)、雙盲研究，評估兩種不同劑量的ianalumab與安慰劑（均聯(lián)合艾曲泊帕）在既往一線糖皮質(zhì)激素治療失敗的原發(fā)性免疫性血小板減少癥（ITP，血小板計(jì)數(shù)<30 G/L）成人患者中的療效和安全性[3]。所有患者均聯(lián)合艾曲泊帕，隨機(jī)分為1:1:1三組，分別接受每月一次、共四次的靜脈注射ianalumab 3 mg/kg、ianalumab 9 mg/kg或安慰劑[3]。主要終點(diǎn)為至治療失敗時(shí)間（TTF），定義為從隨機(jī)分組起至以下任一事件發(fā)生的時(shí)間：隨機(jī)分組8周后血小板計(jì)數(shù)<30 G/L；隨機(jī)分組8周后需救援治療；任何時(shí)間需新ITP治療；無法減/停艾曲泊帕；或死亡[3]。關(guān)鍵次要終點(diǎn)為第6個(gè)月時(shí)達(dá)到持續(xù)血小板計(jì)數(shù)應(yīng)答的患者比例[3]。其他次要終點(diǎn)包括血小板反應(yīng)深度和持續(xù)時(shí)間、患者報(bào)告的生活質(zhì)量和疲勞等[3]。
免責(zé)聲明
參考文獻(xiàn)
1. Primary results from VAYHIT2, a randomized, double-blind, phase 3 trial of ianalumab plus eltrombopag versus placebo plus eltrombopag in patients with primary immune thrombocytopenia (ITP) who failed first-line corticosteroid treatment. Oral presentation at ASH Annual Meeting & Exposition: December 6-9, 2025. |
2. Cuker A, Stauch T,Cooper N et al. Ianalumab plus Eltrombopag in Immune Thrombocytopenia. N Engl J Med. DOI: 10.1056/NEJMoa2515168 |
3. Clinicaltrials.gov. NCT05653219. A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids (VAYHIT2). Accessed November 14, 2025. https://clinicaltrials.gov/study/NCT05653219 |
4. Thomas GB, Xavier M, Stephanie F et al. Ianalumab demonstrates significant reduction in disease activity in patients with Sjögren's Disease: Efficacy and safety results from two global Phase 3, randomized, placebo-controlled double-blind studies (NEPTUNUS-1 and NEPTUNUS-2). Presented at the American College of Rheumatology (ACR) Congress; October 24-29, 2025; Chicago, Illinois. |
5. US Food and Drug Administration. Orphan drug designation: ianalumab—treatment of primary immune thrombocytopenia. Published February 13, 2025. Accessed November 14, 2025. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=1018924 |
6. European Commission. Community register of orphan medicinal products: ianalumab. Updated October 14, 2025. Accessed November 14, 2025. https://ec.europa.eu/health/documents/community-register/html/o3036.htm |
7. Clinicaltrials.gov. NCT05648968. A Study of Efficacy and Safety of Ianalumab in Previously Treated Patients With Warm Autoimmune Hemolytic Anemia (VAYHIA) Accessed November 14, 2025. https://clinicaltrials.gov/study/NCT05648968 |
8. Dörner T, Bowman SJ, Fox R, et al. Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study. Arthritis Rheumatol. 2025;77(5):560-570. doi:10.1002/art.43059 |
9. Clinicaltrials.gov. NCT05350072. Two-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren's Syndrome (NEPTUNUS-1). Accessed November 14, 2025. https://clinicaltrials.gov/study/NCT05350072 |
10. Clinicaltrials.gov. NCT05349214. Three-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren's Syndrome (NEPTUNUS-2). Accessed November 14, 2025. https://clinicaltrials.gov/study/NCT05349214 |
11. Clinicaltrials.gov. NCT05639114. Phase 3 Study to Evaluate Two Regimens of Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 1) (SIRIUS-SLE 1). Accessed November 14, 2025. https://www.clinicaltrials.gov/study/NCT05639114 |
12. Clinicaltrials.gov. NCT05126277. Safety, Efficacy and Tolerability of Ianalumab Versus Placebo, Combination With SoC Therapy, in Participants With Active Lupus Nephritis (SIRIUS-LN). Accessed November 14, 2025. https://clinicaltrials.gov/study/NCT05126277 |
13. Clinicaltrials.gov. NCT06470048. A Clinical Study to Evaluate Ianalumab in Participants With Diffuse Cutaneous Systemic Sclerosis. Accessed November 14, 2025. https://clinicaltrials.gov/study/NCT06470048 |
14. Bowman SJ, Fox R, Dörner T, et al. Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet. 2022;399(10320):161-171. doi:10.1016/S0140-6736(21)02251-0 |
15. Shen N, Ignatenko S, Gordienko A, et al. Phase 2 Safety and Efficacy of Subcutaneous (s.c.) Dose Ianalumab (VAY736; Anti-BAFFR mAb) Administered Monthly over 28 Weeks in Patients with Systemic Lupus Erythematosus (SLE) of Moderate-to-Severe Activity [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). Accessed November 14, 2025. https://acrabstracts.org/abstract/phase-2-safety-and-efficacy-of-subcutaneous-s-c-dose-ianalumab-vay736-anti-baffr-mab-administered-monthly-over-28-weeks-in-patients-with-systemic-lupus-erythematosus-sle-of-moderate-to-severe/ |
16. Bradbury C, Elverdi T, Trautmann K, et al. A phase 2 study of ianalumab in patients with primary immune thrombocytopenia previously treated with at least two lines of therapy (VAYHIT3). HemaSphere. 2025;9(Suppl 1):Abstract S238. Presented at European Hematology Association (EHA) Congress, June 12?15, 2025. Milan, Italy. Accessed November 14, 2025. https://library.ehaweb.org/eha/2025/eha2025-congress/4159389/charlotte.bradbury.a.phase.2.study.of.ianalumab.in.patients.with.primary.html |
17. Novartis. Press release. Novartis to strengthen oncology pipeline with agreement to acquire MorphoSys AG for EUR 68 per share or an aggregate of EUR 2.7bn in cash. February 5, 2024. Accessed November 14, 2025. https://www.novartis.com/news/media-releases/novartis-strengthen-oncology-pipeline-agreement-acquire-morphosys-ag-eur-68-share-or-aggregate-eur-27bn-cash |
18. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-2393. doi:10.1182/blood-2008-07-162503 |
19. Kuter DJ, Mathias SD, Rummel M, et al. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care. Am J Hematol. 2012;87:558-61 |
20. Kuter DJ. The treatment of immune thrombocytopenia (ITP)—focus on thrombopoietin receptor agonists. Ann Blood. 2021;6:27. doi:10.21037/aob-2021-itp-04 |
21. Provan D, Newland AC. Current management of primary immune thrombocytopenia. Adv Ther. 2015;32(10):875-887. doi:10.1007/s12325-015-0240-z |
22. Cooper N, Kruse A, Kruse C, et al. Immune thrombocytopenia (ITP) World Impact Survey (I-WISh): impact of ITP on health-related quality of life. Am J Hematol. 2021;96(2):199-207. doi:10.1002/ajh.26083 |
23. Mingot-Castellano ME, Bastida JM, Caballero-Navarro G, et al. Novel therapies to address unmet needs in ITP. Pharmaceuticals (Basel). 2022;15(7):779. doi:10.3390/ph15070779 |
