瑞士巴塞爾2025年12月10日 /美通社/ -- 諾華近日宣布VAYHIT2三期臨床試驗取得積極結果，該試驗評估了ianalumab聯合艾曲泊帕在既往接受糖皮質激素治療的原發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）聯合艾曲泊帕將ITP疾病控制延長了45%，該結果基于主要研究終點"至治療失敗時間（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間[1,2]。接受ianalumab聯合艾曲泊帕治療的患者，其至治療失敗的中位時間是安慰劑聯合艾曲泊帕組的2.8倍（13.0個月 vs 4.7個月）[1,2]。
詳細數據于第67屆美國血液學會年會（ASH）的最新突破摘要（Late-Breaking Abstracts） 專場公布，并同步發表于《新英格蘭醫學雜志》[1,2]。
"ITP的治療一直以來側重于提升血小板計數，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，持續承受疾病負擔和如疲勞等的癥狀，"麻總百瀚醫院（Mass General Brigham）血液學/腫瘤學 Peggy S. Blitz 講席教授、哈佛醫學院醫學副教授Hanny Al-Samkari博士表示，"VAYHIT2試驗結果令人鼓舞，顯示即使在患者停藥期間也能實現更好的疾病控制，為ITP患者帶來新的希望。"
接受ianalumab（9 mg/kg）聯合艾曲泊帕治療的患者，在第6個月時持續血小板計數改善的比例也顯著高于安慰劑聯合艾曲泊帕治療組（62% vs 39%），達到了關鍵次要終點[1,2]。疲勞改善方面，PROMIS疲勞評分顯示，ianalumab聯合艾曲泊帕組平均下降7.7分，安慰劑聯合艾曲泊帕治療組下降3.6分[1,2]。
"B細胞驅動的自身免疫反應導致ITP患者血小板破壞和出血風險增加。Ianalumab的創新雙重作用機制旨在清除B細胞并阻斷其存活信號。"諾華全球腫瘤開發負責人Mark Rutstein博士表示，"憑借我們在ITP領域多年的經驗，VAYHIT2結果進一步證明ianalumab有望通過每月一次、共四次的靜脈輸注方案，實現持久疾病控制，讓患者無需長期持續治療。"
VAYHIT2評估了兩種劑量的ianalumab，其中9 mg/kg劑量在主要和關鍵次要終點均顯示出統計學顯著改善，3 mg/kg劑量在主要終點達到統計學顯著，關鍵次要終點有數值改善[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： 至治療失敗時間（TTF） |
13.0個月 (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個月 |
關鍵次要終點： 6個月時持續應答率（SR6） |
62.0% (p=0.023a) |
56.9% (p=0.035a) |
39.2 %
|
a. 統計學顯著性所需p值為單側<0.025
Ianalumab耐受性良好，未發現新的安全信號，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生率相當，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%）和輸注相關反應（9 mg/kg組14%，3 mg/kg組8%，安慰劑組8%）[1,2]。中性粒細胞減少癥*在ianalumab組更常見（9 mg/kg組16%，3 mg/kg組12%，安慰劑組2%），大多數病例無需治療或劑量調整即可恢復[1,2]。未有因治療期間不良事件導致永久停藥的情況[1,2]。
VAYHIT2是ianalumab的第三項獲得陽性結果的III期臨床試驗，此前在活動性干燥綜合征成人患者中已有兩項陽性結果[1,4]。諾華計劃于2027年將VAYHIT2數據與正在進行的一線ITP試驗結果（VAYHIT1）一同提交。Ianalumab已獲得美國食品藥品監督管理局（FDA）和歐洲藥品管理局（EMA）的孤兒藥資格認定[5,6]。
*注：中性粒細胞減少癥為特別關注不良事件，包括多種與中性粒細胞、中性粒前體細胞及白細胞減少相關的術語。 |
關于ianalumab
Ianalumab（VAY736）是一種新型全人源單克隆抗體，正在開發用于治療多種B細胞介導的自身免疫性疾病，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）及彌漫性皮膚系統性硬化癥（dcSSc）[3,7-13]。其作用機制通過兩種途徑靶向B細胞：一方面通過抗體依賴性細胞毒作用（ADCC）耗竭B細胞，另一方面，阻斷BAFF-R介導的B細胞功能及存活信號[8]。臨床試驗顯示，ianalumab在干燥綜合征、系統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，諾華于2024年收購了該公司[17]。
關于原發性免疫性血小板減少癥
原發性免疫性血小板減少癥（ITP）是一種罕見的自身免疫性疾病，患者的免疫系統錯誤地攻擊并破壞血小板——血液凝固所必需的細胞[18]。這會導致出血時間延長、易瘀傷和慢性疲勞等癥狀，嚴重影響日常生活[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，難以實現長期疾病控制[20]。現有治療多以維持安全血小板水平和預防出血為主，往往需要長期用藥[20,21]。長期治療負擔和復發的不確定性嚴重影響患者生活質量[19,22]。亟需能夠實現持久反應、減少長期治療負擔的新療法[23]。
關于VAYHIT2
VAYHIT2（NCT05653219）是一項III期、多中心、隨機、雙盲研究，評估兩種不同劑量的ianalumab與安慰劑（均聯合艾曲泊帕）在既往一線糖皮質激素治療失敗的原發性免疫性血小板減少癥（ITP，血小板計數<30 G/L）成人患者中的療效和安全性[3]。所有患者均聯合艾曲泊帕，隨機分為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]。主要終點為至治療失敗時間（TTF），定義為從隨機分組起至以下任一事件發生的時間：隨機分組8周后血小板計數<30 G/L；隨機分組8周后需救援治療；任何時間需新ITP治療；無法減/停艾曲泊帕；或死亡[3]。關鍵次要終點為第6個月時達到持續血小板計數應答的患者比例[3]。其他次要終點包括血小板反應深度和持續時間、患者報告的生活質量和疲勞等[3]。
免責聲明
參考文獻
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