RedHill Biopharma 獲准在俄羅斯進行第 2/3 期 COVID-19 研究

當英國最近批准並在意大利提交類似申請後，俄羅斯批准將 opaganib 用於嚴重 COVID-19 患者以進行第 2/3 期研究的臨床試驗申請
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第 2/3 研究旨在從多達 40 個臨床中心納入 270 名受試者；計劃納入工作將在本月稍後啟動，並計劃於 2020 年第四季提交緊急使用授權申請
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同時，美國第 2a 期將 opaganib 用於嚴重 COVID-19 的研究正在迅速拓展，現已納入超過 25% 患者
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將 opaganib 在以色列用於多達 50 名嚴重 COVID-19 患者的臨床研究也已獲得核准
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與匹配病例對照組相比，根據恩慈使用的嚴重 COVID-19 患者治療結果顯示可對此類患者帶來實益

以色列特拉維夫和北卡羅萊納州拉里格, July 20, 2020 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (Nasdaq: RDHL)（簡稱 RedHill 或「該公司」），是一家專門生物製藥公司，今天宣佈從俄羅斯聯邦衛生部獲批取得臨床試驗授權 (CTA) 申請以進行第 2/3 研究，以評估將 opaganib (Yeliva^®, ABC294640)¹ 用於嚴重 SARS-CoV-2 感染（COVID-19 病因）及肺炎的住院患者。研究最近也已在英國獲准，另外在意大利進行類似的審核申請，目前正在計劃將研究進一步擴展到其他國家。

RedHill 的首席營運主管 Gilead Raday 說：「我們現正使用 opaganib 快速促進 COVID-19 的臨床開發計劃，如取得成功，我們計劃在今年第四季提交緊急使用授權申請。將 opaganib 用於嚴重 COVID-19 患者的第 2/3 期研究已在兩個國家的監管機關獲得核准，而我們正在將研究擴展至其他國家。由於計劃於本月稍後將啟動第 2/3 期研究，考慮到美國第 2a 期研究的納入率超過 25%，RedHill 在相關競爭中處於有利位置，為 COVID-19 住院患者帶來新的潛在實益療法。」  

這項多中心、隨機、雙盲、平行組、安慰劑對照的第 2/3 期研究旨在納入多達 270 名需要住院和補充氧氣治療的嚴重 COVID-19 肺炎患者。受試者將以 1:1 的比例隨機分配接受 opaganib 或安慰劑，加上標準護理。研究的主要終點是在第 14 天之前評估需要插喉和機械呼吸的患者比例。在評估大約 100 名受試者的主要終點時，獨立的數據安全監控委員會 (DSMB) 將進行僅揭盲徒勞中期分析。

該公司亦宣佈經已獲得以色列衛生部批准開展一項研究，以評估將 opaganib 用於多達 50 名嚴重 COVID-19 感染和肺炎的患者。

在一項將 opaganib 用於隨機、雙盲、安慰劑對照的第 2a 期臨床研究中，美國目前也正在進行納入 (NCT04414618)。該研究旨在納入多達 40 名需要住院治療和補充氧氣的嚴重 COVID-19 肺炎患者。此臨床試驗並無統計學意義。

RedHill 最近宣佈，將 opaganib 用於治療嚴重 COVID-19 患者的治療結果經已發佈²。對 5 名嚴重 COVID-19 患者的治療結果進行的分析表示，與同一醫院的回顧性配對病例對照組相比，在恩慈使用 opaganib 治療的患者中，臨床結果和發炎標記均獲得實益。Opaganib 治療組的所有患者均無需機械呼吸即可出院，而匹配病例對照組的 33% 則需要機械呼吸。在 opaganib 治療組中，從高流量鼻導管戒斷的中位時間減少至 10 天，而配對病例對照組則為 15 天。

關於 Opaganib (ABC294640, Yeliva^®)
Opaganib 是新的化學實體，是一種專利的頂級口服鞘氨醇激酶-2 (SK2) 選擇性抑制劑，適應症為抗癌、抗炎和抗病毒活性，及針對多種腫瘤、病毒、發炎和腸胃問題。透過抑制 SK2，opaganib 可影響與癌症生長、病毒複製和病理發炎相關的多種細胞途徑。

Opaganib 原本由總部位於美國的 Apogee Biotechnology Corp. 開發，至今已完成多項成功的臨床前研究，當中涉及腫瘤學、發炎、腸胃道和放射防護模型，以及針對患有晚期實體瘤癌症患者的第 1 期臨床研究。

Opaganib 獲得美國 FDA 用於治療膽管癌的孤兒藥稱號，目前正在晚期膽管癌的第 2a 期研究和前列腺癌第 2 期研究中接受評估。Opaganib 現在也被評估用於治療冠狀病毒 (COVID-19)。

臨床前數據表示，opaganib 具有抗炎和抗病毒活性，並具有減輕肺部發炎疾病（如肺炎）和減輕肺纖維化損害的潛力。早前的一些臨床前研究支持 SK2 在類似冠狀病毒的正向單鏈 RNA 病毒的複制轉錄複合物中的潛在作用，而其抑制作用可能可抑制病毒複製。臨床前的體內研究³已顯示 opaganib 透過降低支氣管肺泡灌洗液中的 IL-6 及 TNF-alpha 水平，成功降低流感病毒感染的死亡率，同時改善銅綠假單胞菌 (Pseudomonas aeruginosa) 誘導的肺損傷。

Opaganib 的開發已獲得美國聯邦和州政府機構授予 Apogee Biotechnology Corp. 的贈款和合約支持，其中包括 NCI、BARDA、美國國防部和 FDA 孤兒藥品開發辦公室。

關於 RedHill Biopharma      
RedHill Biopharma Ltd. (Nasdaq: RDHL) 是一家專門生物製藥公司，專注於腸胃道疾病。RedHill 推廣腸胃道藥物 Movantik^® 用於治療成人阿片類藥物引起的便秘⁴、Talicia^® 用於治療成人幽門螺桿菌 (Helicobacter pylori, H. pylori) 感染⁵，及 Aemcolo^® 用於治療成人旅遊人士的腹瀉問題⁶。RedHill 的關鍵臨床後期開發計劃包括：(i) RHB-204，當中計劃進行關鍵第 3 期肺炎非結核分枝桿菌 (NTM) 感染；(ii) Opaganib (Yeliva^®)，這是針對多種適應症的一流 SK2 選擇性抑制劑，涉及針對 COVID-19 的第 2/3 期計劃及針對前列腺癌和膽管癌正在進行中的第 2 期研究；(iii) RHB-104，當中克隆氏症的首個第 3 期研究獲得正面結果；(iv) RHB-102 (Bekinda^®)，當中在急性腸胃炎和胃炎的第 3 期研究中獲得正面結果，及在 IBS-D 的第 2 期研究中獲得正面結果；(v) RHB-106，這是一種膠囊大腸制劑，以及 (vi) RHB-107，這是第 2 期一流的絲氨酸蛋白酶抑制劑，針對癌症和腸胃發炎，目前也接受 COVID-19 的評估。如欲了解更多關於公司的資訊，請瀏覽 www.redhillbio.com。

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control and cannot be predicted or quantified, and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, the risk that the clinical condition of the patients treated with opaganib will not continue to improve and may worsen, the risk that the U.S. and Israel Phase 2a clinical studies evaluating opaganib will not be successful; the risk that the Company will not initiate the Phase 2/3 study in the UK, Russia or Italy and will not expand this study to a multinational study with sites in additional countries; the risk that other COVID-19 patients treated with opaganib will not show any clinical improvement; the risk that clinical trials with opaganib in Israel, the U.S., Russia, the UK, Italy or elsewhere for the treatment of COVID-19, if conducted at all, will not show any improvement in patients; the development risks of early-stage discovery efforts for a disease that is still little understood, including difficulty in assessing the efficacy of opaganib for the treatment of COVID-19, if at all; intense competition from other companies developing potential treatments and vaccines for COVID-19; the effect of a potential occurrence of patients suffering serious adverse events using opaganib under the compassionate use programs, as well as risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, pre-clinical studies, clinical trials, and other therapeutic candidate development efforts, and the timing of the commercial launch of its commercial products and ones it may acquire or develop in the future; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its pre-clinical studies or clinical trials or the development of a commercial companion diagnostic for the detection of MAP; (iii) the extent and number and type of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates and Talicia^®; (v) the Company’s ability to successfully commercialize and promote Talicia^®, and Aemcolo^® and Movantik^®; (vi) the Company’s ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build and sustain its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and the results obtained with its therapeutic candidates in research, pre-clinical studies or clinical trials; (ix) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and commercial products and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; (xii) estimates of the Company’s expenses, future revenues, capital requirements and needs for additional financing; (xiii) the effect of patients suffering adverse experiences using investigative drugs under the Company's Expanded Access Program; and (xiv) competition from other companies and technologies within the Company’s industry. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on March 4, 2020. All forward-looking statements included in this press release are made only as of the date of this press release. The Company assumes no obligation to update any written or oral forward-looking statement, whether as a result of new information, future events or otherwise unless required by law.

注意：為方便讀者，本新聞稿為公司以英語發表之正式新聞稿的翻譯版本。

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¹ Opaganib 是一種試驗性新藥，尚未有商業分銷。

² 本文作者為 Shaare-Zedek Medical Center 的 Ramzi Kurd 醫學博士；Shaare-Zedek Medical Center 及希伯來大學醫學院的 Eli Ben-Chetrit 醫學博士；Shaare-Zedek Medical Center 的 Hani Karameh 醫學博士及 Shaare-Zedek Medical Center 及希伯來大學醫學院的 Maskit Bar-Meir 醫學博士。全文載於以下網址：https://www.medrxiv.org/content/10.1101/2020.06.20.20099010v1?rss=1。

³ Xia C. et al. Transient inhibition of sphingosine kinases confers protection to influenza A virus infected mice. Antiviral Res. 2018 Oct; 158:171-177. Ebenezer DL et al. Pseudomonas aeruginosa stimulates nuclear sphingosine-1-phosphate generation and epigenetic regulation of lung inflammatory injury. Thorax. 2019 Jun; 74(6):579-591.

⁴ Movantik^® (naloxegol) 的完整處方資訊載於：www.Movantik.com。 

⁵ Talicia^® (omeprazole magnesium, amoxicillin 及 rifabutin) 的完整處方資訊載於：www.Talicia.com。     

⁶ Aemcolo^® (rifamycin) 的完整處方資訊載於：www.Aemcolo.com。 

source: RedHill Biopharma Ltd.