A. Cerebraca Wafer 對抗人類惡性腦膠質瘤

“標靶”藥物暨投遞裝置CerebracaTM wafer,治療人類惡性腦膠質瘤

🏆 台灣、美國FDA核准執行臨床試驗
🏆 美國FDA孤兒藥 Designation
🏆 科技部傑出技轉貢獻獎
🏆 第11屆國家新創獎
🏆 政府計畫補助
🏆 政府生技新藥認證

      惡性腫瘤持續高居國人十大死因之首,根據美國癌症協會 (American Cancer Society, ACS )以及美國腦瘤病例登錄中心 (Central brain tumor registry, CBTRUS)的統計報告顯示,每年估計約有兩萬筆的腦瘤患者新病例產生,台灣每年約有四百名惡性膠質腦瘤新病例。多型性神經膠母細胞瘤 (glioblastoma multiformis; GBM)是相當惡性的腦部腫瘤,切除後的復發率也非常高,GBM復發後的病患,平均存活時間只有6.5個月。 

      由林欣榮、韓鴻志、邱紫文 教授領導的新藥開發團隊 以以中藥研發小分子抗癌標靶新藥新藥EF001,並結合生醫材料聚酸酐來製造成 Cerebraca™ wafer。Cerebraca™ wafer之安全性與有效性已有多種動物模式驗證。例如,以大鼠為實驗對象,植入 Cerebraca™ wafer後將藥物釋放至腦瘤區域,動物平均存活時間比無治療組別延長2.5倍。特別是Cerebraca™ wafer的主成分 EF001是一個多標靶的小分子藥物,相關論文十九篇分別發表在Journal of Neurochemistry、Neuro-Oncology、Biochemical pharmacology、Clinical Cancer Research與Oncogene等著名國際期刊;並取得臺灣、中國大陸、美國、日本及歐盟等多國專利。標靶藥物EF001對Axl、端粒酶 (telomerase) 與去氧核醣核酸修復酶 (O6-methylguanine-DNA-methyltransferase, MGMT)具專一性。Cerebraca™ wafer 有效成分 EF001可被緩慢釋放並擴散至周邊腦組織,以清除手術無法清除之腫瘤細胞;進一步研究中發現,EF001有效的降低腦瘤細胞對於現行一線腦瘤化療藥物TMZ之抗藥性,顯示標靶新藥 Cerebraca™ wafer與 TMZ並用後,將能達到更佳的治療效果 (圖一)。2016 年8月已通過美國 FDA及台灣 TFDA 之 IND (investigate new drug; 新藥臨床試驗許可),長弘生物科技公司委託花蓮慈濟醫院及台北三軍總醫院於2017年展開第I到IIa期臨床實驗 現已完成六例受試者,進展順利且通過安全性評估,第一例病人仍然存活,並已超過13 個月,高於目前GBM復發後的平均存活時間6.5個月。預計2019年將進入臨床二期,並加強尋求國際合作發展機會。

      New targeted therapy drug CerebracaTM Wafer is a biodegradable wafer for interstitial implantation comprises a small molecule EF001 and bio-degradable Copolymer. 

      IND application approved by USFDA and TFDA. Phase I/IIa clinical trial is presently ongoing. Looking for the opportunity to cooperate with international pharmaceutical companies or venture capitals.
      The anti-glioblastoma pharmacology effect of the API, identified in yellowish brown root of the plant Angelica sinensis, a well-known Chinese medicine, were firstly evaluated in several human cancer cell lines, including a human glioblastoma multiforme (GBM) cell line. These antitumor activities were contributed by the effects of API in suppression of telomerase level (Lin et al. 2011), up-regulation of nuclear receptor Nur77 (an apoptosis mediator) (Lin et al., 2008), reducing glioma migration and invasion mediated by Axl-1 tyrosine receptor (Yen et al., Oncogene, 2016) and tumor stem cell Sox-2 genes (Yen et al., 2017). More importantly, the EF001 further showed the effects on reversing Temozolomide (TMZ) resistance by suppressing O6-methylguanine-DNA-methyltransferase (MGMT) mRNA and protein expression (Harn et al., 2013). Taken together, the EF001 targeted multiple tumor associated genes including Axl, EZH2, SOX2, telomerase, and DNA repair gene MGMT.
      CerebracaTM wafer was designed to overcome the drug delivery limited by blood-brain barrier. This novelty contributes the efficient effects on survival (2.5 time prolonged more than untreated group). To date, chemical manufacturing and control (CMC), preclinical efficacy and preclinical safety assessment and other tests of CerebracaTM Wafer were completed. The IND application of CerebracaTM Wafer phase I/IIa clinical trial had been approved by FDA and TFDA. This clinical trial was performed at Tzu-Chi University Hospital in Haulien and Tri-Service General Hospital in Taipei city, Taiwan. So far, we have finished cohort II six patients study. No safety issue is found. The first patient has been extending 13 months. We are looking for the opportunity to cooperate with international pharmaceutical companies or venture capitals. 

      Cerebraca Wafer是本公司研究團對研發出對抗人類惡性腦膠質瘤 (GBM) 新藥。已擁有包含台灣的多國專利。公司產品係一種醫藥配方,該醫藥配方含有 EF-001及一生物可分解聚合物彼等係混合在一起,成為一種緩慢釋出抗癌藥物之新劑型。動物試驗中已驗證 Cerebraca Wafer能夠抑制腦瘤的生長,並延長試驗動物的平均存活期。如下圖所述:

圖一:Cerebraca Wafer釋放之有效成分能夠有效毒殺種瘤細胞

圖二:Cerebraca Wafer於皮下腫瘤模式中,能夠有效抑制腫瘤生長速率 (減少腫瘤生長大小)

圖三:Cerebraca Wafer能夠抑制自發性腦瘤之生長

圖四:Cerebraca Wafer能夠延長原位惡性腦瘤腫瘤模式動物的存活

Cerebraca Wafer開發狀態

      Cerebraca Wafer目前正在執行 Phase I/IIa期臨床試驗,若有興趣深入了解,可參考本臨床試驗招募海報,向試驗主持人尋求更多的資訊。