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Saturday, September 6, 2014

閻紫宸 (引)王瑞瑜、王長怡 拼 聯合生物製藥 攻 資本市場 (2014-2015)

兩位女強人合作 王瑞瑜、王長怡搶攻全球1.5兆大餅 攜手聯亞跨入製藥,台塑生醫十年布局到位  作者:滕淑芬  攝影:陳之俊 出處:20149月號《遠見雜誌》 339期 為了全力進軍生技產業,台塑生醫結盟聯亞,成立聯合生物製藥,並斥資12億元在新竹興建製藥廠,希望憑藉雙方優勢3年內讓新藥上市。 這一段時間以來,許多人總是這樣形容這個合作案:「一位是台塑集團創辦人王永慶的女兒王瑞瑜,一位是前國大代表、《中外雜誌》創辦人王成聖的女兒王長怡,」兩位女企業家攜手,今年初成立了聯合生物製藥公司,希望搶攻全球500億美元(約台幣15000萬元)的蛋白質藥物市場。這個合作案中,台塑生醫將投資台幣12.6億元在新竹湖口工業區興建製藥廠,2016年完工後,將會是全台最大的蛋白質藥物生產基地。   

契機〉技術、人才齊全 一拍即合 以化妝品、清潔用品和保健食品為主力的台塑生醫,為何選在此時跨入生物製藥?在台塑大樓接受《遠見》採訪的台塑生醫董事長王瑞瑜說,這是她10年前創業就有的夢,當時就想整合集團資源,同時投入「生活、生物、生化、醫材、醫藥、醫學」這六大領域,但因條件不足,只能從「最低階」的生活用品入手。10年前從小苗灌溉,慢慢茁壯後,兩年前才透過長庚醫院產學中心主任閻紫宸引介,認識1985年即成立生技公司的王長怡。王瑞瑜說,未來是蛋白質藥物的天下,聯亞有技術,加上人才到位,技術成熟,走到這一步,「可以說是天時地利人和。」王長怡專業出身。台大化學系畢業後,在美國洛克菲勒大學取得免疫學博士學位,28歲進入全美最大的史隆凱特林癌症研究中心(Memorial Sloan Kettering Cancer Center),是該中心最年輕的實驗室主任。不願只被定位在研發主管,1985年她在紐約長島創立聯合生物醫學公司(UBI),研發的C型肝炎檢驗試劑,是第一件成功商品化的產品,1997年打入歐洲,占有13歐洲市場。1998年受經濟部邀請回台,在台灣成立分公司。

聯亞生技董座:3年內六大事業群完成切割上市 精實新聞 2014-01-16 18:43:40 記者 蕭燕翔 報導 聯亞生技與台塑生醫16日對外宣布,合資成立單株抗體開發公司聯合生物製藥,預計台塑集團將取得25%股權;聯亞生技董事長王長怡(附圖)表示,未來三年六大事業群完成切割上市,五年內希望有一個全新藥品問世,而聯亞也將扮演集團內類似控股及技術整合平台的角色,並透過與策略性投資人合資,產生綜效。 聯亞生技成立於199810月,創辦人暨董事長王長怡1985年在美國創立美國聯合生物醫學(UBI)1996-1998年應前經濟部長尹啟銘(時任工業局長)之邀,回來與政府合資設立聯亞生技,目前聯亞生技的股東包括UBI六成,國發基金、台糖及耀華玻璃等泛官方持股約四成。 而聯亞/UBI共同開發系列創新動物合成(月太)疫苗產品包括第一代豬口蹄疫O型合成(月太)疫苗、第二代豬/牛口蹄疫多架合成(月太)疫苗、第一代及第二代公豬去勢合成(月太)疫苗、豬藍耳病疫苗及豬環狀病毒疫苗,2012年透過母公司UBI與國知名動物保健品公司簽署授權合約,在國際市場進行合作,除簽約的前期金外,未來也將依照設定里程碑及銷售額認列里程碑款及權利金。  王長怡也表示,聯亞生技旗下有六大事業群,20134月完成第一個事業群的分割,與長期合作夥伴萬菱藥品與瑩碩醫藥合資成立特殊學名藥廠-歐帕醫藥(AUPA),因該部分非屬聯亞的核心事業,聯亞持股三成、位居第二大股東。 次與台塑生醫合資的單株抗體開發公司聯合生物製藥,聯亞則持股75%,該公司將專注單株抗體藥品的開發,目前已有七項產品Pipeline,近期也將進駐竹北生醫園區,並於湖口基地投資建造兩線2千公升級的單株抗體藥品製造廠,預計2015年底完工,王長怡說,聯合生物製藥將在今年67月公開發行,11月登錄興櫃,明年10月上市() 王長怡表示,除兩家已分割成立的事業群外,其他包括創新阿茲海默症治療系合成胜(月太)疫苗與相關神經退化疾病產品線、創新動物疫苗事業、非單株抗體蛋白質藥品及醫療器材等四大事業群,事業群將在產品具深度及尋求有互補的策略夥伴後,切割出去,預計今年還會有創新阿茲海默症治療系合成胜(月太)疫苗與相關神經退化疾病產品線、創新動物疫苗事業完成分割,三年內將完成六大事業群的分割上市。 在產品進度上,聯亞/UBI共同開開發的創新阿茲海默症疫苗UB-311,已於2011年底完成1期臨床試驗,2013年獲准進入2a期臨床試驗於台大醫院、台北榮總及長庚醫院進行,並獲得美國Eli Lilly公司同意本臨床試驗使用其特有的AV-45生物標記/顯影產品,結合正子斷層掃瞄(PET)偵測早期阿茲海默症病人,以提升病人篩選準確性。  另外,非單株抗體蛋白質領域則擁有包括紅血球生成素(EPO)生物相似性藥品及具特有平台技術的長效型蛋白質藥物產品線,此等長效性蛋白質藥物可增加藥物於血中濃度,減少注射藥物次數,提升病人用藥便利性,預計2015年進行事業切割成立子公司。  

Halaven (賀樂維/ Eribulin) :德国药物评估IQWiG 見解!

抗乳腺癌新药Eribulin的疗效尚存争议 发布时间:2012-8-26 21:13:12 Eribulin(商品名为Halaven)是新型的局限性晚期或转移性乳癌治疗药物,20113月上市。根据"医药产品市场的改革法案"(AMNOG),德国药物评估局(IQWiG)将Eribulin药物疗法与目前的标准疗法相比,是否能使患者受益更多进行了审核。评估结果显示:现有证据表明乳癌患者若不适合使用紫杉烷类或蒽环类药物,使用Eribulin可能延长患者的生存时间。然而,Eribulin具体能够让患者生存期延长多久,目前还不得而知。与一直使用紫杉烷类或蒽环类药物治疗的患者相比,使用Eribulin没有任何的生存优势。总的来说,无证据表明增加Eribulin使乳腺癌患者受益。

乳癌第三線希望_海洋來源藥物: Halaven (賀樂維/ Eribulin)

201011FDA批准上市新药甲磺酸艾日布林(eribulin mesylate 2010-12-15 20:10:36 来源:有机化学网 1115,美国食品药品管理局(FDA)批准Halaven用于治疗至少已接受过两次晚期疾病化疗的转移性乳腺癌患者。 Halaven是一种从海洋生物海绵Halichondriaokadai中提取的大环内酯类化合物halichondrinB的衍生物,是一种具有化学活性的物质。其作用机理可能是通过直接与微管蛋白结合抑制有丝分裂,通过抑制微管生长,抑制癌细胞生长而发挥治疗作用。在接受Halaven治疗之前,患者应首先接受蒽环类以及针对早期或晚期乳腺癌的基于紫杉烷的化学疗法。

Halaven (賀樂維/ Eribulin): 哈佛發明/Eisai發揚光大(上市)

艾日布林(Eribulin)-天然产物衍生的抗癌药 (2012-02-24 04:51:41)  艾日布林(Eribulin)用于治疗曾接受至少两种化药治疗的转移性乳腺癌。20101115FDA批准上市,商品名Halaven,Eisai公司开发。 艾日布林(Eribulin)是海洋天然产物Halichondrin B的类似物。Halichondrin B1986年从海绵Halichondria okadai中分离出来的具有抗癌活性的天然产物。在哈佛大学的Y Kishi研究小组对Halichondrin B的全合成研究中,发现了比Halichondrin B结构简单,药效更好的Eribulin

 

Halaven (賀樂維/ Eribulin) 拼 肺癌(NSCLC)適應症 (僵局 !)

Eribulin在一项晚期非小细胞肺癌研究中失败 作者:王丽wl 来源:医脉通 发布时间:2014-08-14 11:23:18一项初步分析表明,甲磺酸艾日布林(Haloven)未能达到其改善预治疗的晚期非小细胞肺癌(NSCLC)患者总生存期(OS)的终点指标,甲磺酸eribulin的研发者Eisai宣布。研究详情  302研究是一项全球性,多中心,随机,开放标签III期试验,对eribulin(艾日布林)的疗效和安全性进行了研究,并与单一治疗医师选择(TPC)药物(包括多西他赛,培美曲塞,吉西他滨或长春瑞滨)进行了比较。"我们知道,非小细胞肺癌是一种难治性肿瘤类型,除了之前的两个治疗方案外,目前尚无公认的标准化疗方案,仍存在远未满足的医疗需求。" Eisai产品研发系统肿瘤产品研发部主任,Kenichi Nomoto博士在一份声明中说。"在这项研究中,虽然与TPC相比,eribulin没有显示出OS方面的改善,但试验表明,eribulin在至少进行2种治疗方案治疗的晚期NSCLC患者身上表现出抗癌活性,进一步的分析正在进行中。这些结果不会影响当前Halaven适应症的审批。"  这项研究共对540例晚期非小细胞肺癌患者进行了研究,这些患者在至少进行2种治疗方案(其中包括一种含铂治疗方案)治疗晚期疾病后仍出现疾病进展。据初步分析,两组中位OS9.5个月(HR=1.16P =0.1343)。初步安全性分析表明,eribulin组最常见的不良反应是食欲减退,白细胞减少,脱发,恶心和疲劳,这与eribulin已知的安全性一致。Eisai宣布,该研究的完整结果将在未来会议上公布。  研究人员进行了一项II期研究,对采用含铂双药化疗治疗期间或治疗后出现疾病进展的晚期非小细胞肺癌患者应用eribulin治疗。研究发现,eribulin具有活性,且可耐受,可作为非小细胞肺癌的二线或以上的化疗。在这项研究中,两组患者(紫杉类预治疗和紫杉类药物初治)接受了甲磺酸eribulin1.4mg /m2)治疗,2-5分钟静脉滴注,1815天给药一次,28天为一疗程。为了评估第二给药方案的耐受性,紫杉类预治疗患者在18天(21天为一疗程)接受eribulin治疗。根据研究结果,103例患者接受eribulin治疗,ORR 9.7%(所有部分缓解[PR])。缓解中位时间,无进展生存期和总生存期分别为5.83.4,和9.4个月。该研究中最常见的治疗相关不良事件为中性粒细胞减少(54%),疲劳(49%),恶心(38%),脱发(32%)贫血(29%),和神经病变(23%)。因中性粒细胞减少(15天),28天一疗程出现许多剂量延迟,中断,或遗漏,而21天一疗程的耐受性良好。Eribulin是首个大田软海绵素类微管动力学抑制剂,具有新型作用机制。201011月,在美国首个获批用于治疗转移性乳腺癌。Eribulin还正在研究用于治疗卵巢癌,尿路上皮癌和骨肉瘤。  编译自:Eribulin Does Not Improve OS in Advanced NSCLC. OncLive, Aug 11, 2014. 

英國NICE 對 Halaven (賀樂維/ Eribulin) 持保留態度 !!! 捷克 OK !

NICE final "no" to Halaven UK NEWS | APRIL 03, 2012 5  LYNNE TAYLOR In final guidance issued today, the National Institute for Health and Clinical Excellence (NICE) has rejected the use of Eisai's Halaven (eribulin) in locally-advanced or metatastic breast cancer which has progressed after at least two chemotherapeutic regimens for advanced disease. Evidence presented to NICE's independent advisory committee indicated that the drug may help some patients live for a little longer, but it also caused more undesirable side effects than other, already-available treatments, and the panel also felt that its effects on health-related quality of life had not been adequately assessed, said NICE's executive director, Sir Andrew Dillon. Hatfield, UK, 6 January 2014 – Halaven® (eribulin) has received reimbursement approval in the Czech Republic as a highly innovative drug for patients with metastatic breast cancer, effective from the 1 January 2014. Eribulin is the first, single-agent chemotherapy to demonstrate a prolonged overall survival in patients with heavily pre-treated advanced breast cancer, compared to other single agent chemotherapies.[1]  "The reimbursement of eribulin in the Czech Republic is an important step forward for women with metastatic breast cancer," says Professor MUDr. Bohuslav Melichar, PhD, the Scientific Secretary of the Czech Society for Oncology. "These patients urgently need new treatment options and in particular, therapies which have demonstrated an overall survival benefit in heavily pre-treated patients. The advent of eribulin will be welcomed by patients and doctors across the country."  Breast cancer is the most common cancer in Czech women and accounts for nearly 25% of all newly diagnosed malignancies in the female population.[2] More than 6,400 people are diagnosed with breast cancer each year in the Czech Republic[3] and metastatic disease will develop in approximately 30% of cases.  "Metastatic breast cancer continues to affect many women across Europe. We are pleased that the Czech health authorities recognise the innovative drug status and clinical value eribulin may offer to women with locally advanced or metastatic breast cancer," commented MUDr, Miloš Živanský, Medical Director of CEE in Eisai. "The reimbursement in the Czech Republic underscores the potential importance of this treatment and Eisai will work closely with local health authorities to ensure that women in the Czech Republic have rapid access to a treatment that has a proven overall survival benefit."  Eribulin received European Commission approval on 17 March 2011 based on the results of the pivotal Phase III EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) Versus Eribulin E7389) study. Eribulin is now available in 50 countries worldwide.  In the EMBRACE study population (n=762), eribulin was shown to prolong overall survival in heavily pre-treated patients with metastatic breast cancer by 2.5 months compared to patients receiving Treatment of Physicians Choice (TPC), representing a mix of real-life treatment choices (eribulin 13.1 months vs. TPC 10.6 months, HR 0.81 (95% CI 0.66, 0.99) p=0.041).[4] Updated data confirmed that patients treated with eribulin survived a median of 2.7 months longer than patients who received treatment of physician's choice (overall survival of 13.2 months versus 10.5 months, respectively, HR 0.81 (95% CI 0.067, 0.96), nominal p=0.014).4 A pre-planned analysis of patients from Region 1 of the study (North America/Western Europe/Australia) showed a significant overall survival benefit of eribulin over TPC of 3.0 months (p=0.009).4  The most commonly reported adverse reactions among patients treated with eribulin were asthenia (fatigue), neutropenia, alopecia (hair loss), peripheral neuropathy (numbness and tingling in arms and legs), nausea and constipation.4  Eisai is committed to developing and delivering highly beneficial new treatments to help improve the lives of people with cancer. Built on scientific expertise, Eisai is supported by a global capability to conduct discovery and preclinical research, and develop small molecules, therapeutic vaccines, and biologic and supportive care agents for cancer across multiple indications. 

Halaven® (eribulin)  Eribulin is a non-taxane, microtubule dynamics inhibitor indicated for the treatment of patients with breast cancer who have previously received at least two chemotherapeutic regimens for metastatic disease and whose prior therapy should have included an anthracycline and a taxane. Eribulin belongs to a class of antineoplastic agents, the halichondrins, which are natural products, isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics without affecting the shortening phase and sequesters tubulin into non-productive aggregates. 

Global Phase III Clinical Study 305 (EMBRACE)4  EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) Versus Eribulin E7389) was an open-label, randomised, global, multi-centre, parallel two-arm study designed to compare overall survival in patients treated with eribulin versus a Treatment of Physician's Choice (TPC) arm. TPC was defined as any single-agent chemotherapy, hormonal treatment or biologic therapy approved for the treatment of cancer; or palliative treatment or radiotherapy administered according to local practice. The study included 762 patients with metastatic breast cancer who previously had been treated with at least two and a maximum of five prior chemotherapies, including an anthracycline and a taxane. The vast majority (96%) of patients in the TPC arm received chemotherapy.  In the total Phase III EMBRACE study population, eribulin was shown to prolong median overall survival in heavily pre-treated patients with metastatic breast cancer compared to patients receiving TPC by 2.7 months (13.2 vs 10.5 HR 0.81 (95% CI 0.067, 0.96) nominal p=0.014). A pre-planned analysis of patients from Region 1 of the study (North America/Western Europe/Australia) showed a significant median overall survival benefit of eribulin over TPC of 3.0 months (nominal p=0.031).  The most commonly reported adverse reactions among patients treated with eribulin in the EMBRACE study were fatigue (asthenia), a decrease in infection-fighting white blood cells (neutropaenia), hair loss (alopecia), numbness and tingling in arms and legs (peripheral neuropathy), nausea and constipation. Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in less than 5% of the patients involved in the EMBRACE trial. Neutropaenia only led to eribulin discontinuation for 0.6% patients. Death due to serious side effects, discontinuation and dose interruptions to treatment were lower in the eribulin arm of the trial compared with the TPC arm. 

Metastatic Breast Cancer Over 300,000 women are diagnosed with breast cancer in Europe every year, of whom about one third subsequently develop metastatic disease.[5],[6] Metastatic disease is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body. 

About Eisai Eisai is one of the world's leading research and development (R&D) based pharmaceutical companies and we define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call human health care (hhc).  Eisai concentrates its R&D activities in three key areas: 

 Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc.

 Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight loss

 Vascular/Immunological reaction including: thrombocytopenia, rheumatoid arthritis, psoriasis, inflammatory bowel disease 

With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 10,000 people worldwide. From its EMEA Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business operations to include Europe, the Middle East, Africa, Russia and Oceania (EMEA). Eisai EMEA has sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Czech Republic, Slovakia, the Netherlands, Belgium, Luxembourg, Russia and the Middle East.

晚期乳癌治療(Halaven (賀樂維/ Eribulin)給付(增加OS 2.7月) 台灣健保署 OK! 藝術vs異數 !

有關「衛采製藥股份有限公司」建議將用於轉移性乳癌第三線治療之新成分新藥Halaven 0.5mg/mL Solution for injection (eribulin mesylate)納入健保給付案。

說明:詳附錄會議資料討論案第3案之簡報內容。

結論: (1) 蔡代表桂華反映,由於本會議之議案多屬醫療專業,其作為付費者代表,每次會議均希望能全程參與,為消費者把關,惟醫界代表於會議進行中相繼離席,致無法多聽取醫界意見,恐難以充分瞭解議案,陳述意見。 (2) 依衛生福利部函釋,內政部公布之會議規範非屬中央法規標準法所稱之法規命令,並不具有強制性之規範效力,各機關、團體倘另定有議事規則時,應優先適用各該議事規則。依本會議之議事規則,本會議為保險人與各界就藥物給付事項溝通之平台,各界代表於會中陳述意見、共同討論,相關議案之決定,以與會代表之共識為原則。 (3) 癌症新藥之價值並非僅由可延長之存活期長短來判斷,而是須考量各項癌症之治療現況,以及新藥對該項癌症治療進展可能帶來之影響,即每一個階段的治療突破均代表下一階段臨床治療突破的基礎,逐步累積才能有數月或數年之存活結果;次外,基於本會議累積討論案之經驗,特別是癌症藥品,究竟每獲得1個存活年,依本土資料,需付出多少費用才符合成本效益〔ICERincremental cost effectiveness ratio,增加成本效益比值)〕,已成為我們必須嚴肅面對,考慮訂定之課題。 (4) 對於曾接過兩種以上化學藥物治療之轉移性乳癌患者,若療效不佳時,目前尚無標準之治療方法,且乳癌相對於其它癌症有較多治療藥品可供使用,臨床醫師會儘量治療病人延長存活。因此,對於經過多種藥物治療仍失敗的乳癌而言,新藥之臨床試驗欲達到較既有治療藥品有顯著延長整體存活期之結果,實屬不易。本案藥品依廠商所提之實證資料顯示,較現有治療方法可增加整體存活期(overall survival, OS) 2.7,故同意納入健保給付,屬2A類新藥。 (5) 對於曾接過兩種以上化學藥物治療,其療效仍不佳之轉移性乳癌患者,目前尚無標準之治療方法,且多數採用多種藥物合併治療,因無適當之核價參考品,故本案藥品以國際最低價(法國,12,715元)核價。 (6) 另,本案藥品進行之本土經濟研究報告,其報告品質經評為品質良好,可予加算4%,核算為13,223元〔12,715(/)× (1+ 4%)= 13,223(/)〕,惟高於廠商建議價12,715元,故依廠商建議價核算支付價為每支12,715元。 (7) 給付規定:適用藥品給付規定通則及附件3之規定。