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Tuesday, May 5, 2015

Tokai Pharma精準醫療 將執行phase III trial: galeterone for AR-V7 positive castration-resistant prostate cancer (CRPC)

Tokai Pharma (TKAI), Qiagen (QGEN) Expansion Collaboration for AR-V7 Companion Diagnostic5/4/2015 Tokai Pharmaceuticals, Inc. (NASDAQ: TKAI), a clinical-stage biopharmaceutical company focused on developing novel therapies for prostate cancer and other hormonally driven diseases, today announced an expansion of the agreement with Qiagen (NASDAQ: QGEN) for the development and commercialization of an AR-V7 companion diagnostic for use with galeterone. Under the expanded agreement, Tokai will receive the exclusive right from Qiagen to its newly acquired circulating tumor cell (CTC) enrichment technology for use with galeterone, which will be incorporated into the companion diagnostic already under development by Qiagen."We are pleased to be expanding our partnership with Qiagen with exclusive access to their newly acquired CTC enrichment technology for use with the AR-V7 companion diagnostic for galeterone," stated Jodie Morrison, president and chief executive officer of Tokai Pharmaceuticals. "This access adds further support to our growing IP portfolio for galeterone for AR-V7 positive castration-resistant prostate cancer (CRPC). Qiagen is a global leader in liquid biopsy-based solutions for precision medicine and has the expertise to commercialize the companion diagnostic around the world. This global capability will be critical as we work to bring galeterone to prostate cancer patients who test positive for AR-V7, which has been linked to non-responsiveness to commonly used oral therapies. It is our belief that future availability of this companion diagnostic for AR-V7 will allow prostate cancer patients and their physicians to make more informed decisions regarding their care." Development of an AR-V7 companion diagnostic for use with galeterone has been underway since October 2014. Qiagen's newly acquired CTC technology was utilized in the AR-V7 assay methods developed by the Johns Hopkins University licensed by Tokai in January. Tokai and Qiagen expect that development of the AR-V7 clinical trial assay will be completed in the first half of 2015 prior to the start of the ARMOR3-SV AR-V7 metastatic CRPC registration clinical trial.AR-V7 positive prostate tumors express a truncated form of the androgen receptor (AR). These truncated ARs are missing the C-terminal end of the receptor that contains the ligand binding domain. In 2014, the Johns Hopkins University, in a prospective study using the Qiagen technology to isolate and enrich CTCs and an assay to determine AR-V7 status, demonstrated poor responsiveness to Zytiga® (abiraterone acetate) and Xtandi® (enzalutamide), two commonly used oral therapies for metastatic CRPC. The Company believes that galeterone has the potential to treat patients with AR-V7 based on data from preclinical studies and retrospective data in patients with C-terminal loss, the most common form of which is AR-V7, from the Company's Phase 2 ARMOR2 trial of galeterone."Our partnership with Tokai Pharmaceuticals, one of the collaborations which we are pursuing with pharma in this area, is expected to result in a liquid biopsy, CTC-based test for the AR-V7 splice variant in the first half of this year, with the potential to enhance outcomes for prostate cancer patients," said Peer M. Schatz, chief executive officer of Qiagen. "Following the success of the first-ever regulated companion diagnostic for solid tumors based on molecular biomarkers from a liquid biopsy in Europe, we are expanding our portfolio of highly accurate tests that analyze samples of body fluids that are non-invasive and more accessible than traditional tissue biopsies. Our liquid biopsy portfolio holds potential to create valuable insights and improve outcomes for patients."

 

Galeterone (TOK-001 or VN/124-1) is a novel antiandrogen under development by Tokai Pharmaceuticals for the treatment of prostate cancer. It possesses a unique dual mechanism of action, acting as both an androgen receptor antagonist and an inhibitor of CYP17A1, an enzyme required for the biosynthesis of the androgens. As of the second half of 2014, galeterone is in phase III clinical trials for castration-resistant prostate cancer.

 


ARMOR2: Galeterone in progressive CRPC patients who have failed oral therapy.

Meeting: 2014 Genitourinary Cancers Symposium

Citation: J Clin Oncol 32, 2014 (suppl 4; abstr 71)

Background: Galeterone is a first-in-class multitargeted oral steroid analog; it suppresses prostate cancer by a combination of AR modulation (antagonism and degradation) and CYP17 inhibition. Safety and proof of concept of galeterone in CRPC was assessed in ARMOR1. Galeterone was reformulated by spray dry dispersion technology (SDD) to optimize PK and remove food effect. ARMOR2 (NCT 01709734) is an open label, 2-part phase 2 trial that evaluates safety and efficacy of SDD galeterone in 4 populations of CRPC patients. These results report Part 1.

Methods: Objectives of Part 1: confirm dose equivalence of SDD formulation with evaluation of PK, safety and PSA response. Metastatic (M1) and non-metastatic (M0) treatment naïve CRPC pts enrolled to groups of 1,700, 2,550 or 3,400 mg PO daily. An abiraterone refractory (Abi-R) group of 3 patients opened at 2,550mg. Results: 28 were enrolled in part 1. Safety: All groups were safe by IMC assessment. There were 4 grade 3 adverse events. 2 were unrelated to study drug. 2 had transient G3 ALT elevations (did not recur with rechallenge). There was no AME: supplemental steroids were not required. G4 angioedema occurred in a pt receiving lisinopril (known association with angioedema). Efficacy: PSA response was improved compared to ARMOR1 (AACR 2012. Taplin et al abstract: CT-07). At early follow up Abi-R pts showed improvements in PSA with 1 PSA30% response, 2 with stablized PSA (decline in PSA-V from +0.44 to -0.39 ng/day). Conclusions: Galeterone in SDD formulation is tolerated at doses up to 3,400mg daily. SDD galeterone provides improved PSA response and durability vs. prior formulation. There is evidence of activity in abiraterone refractory patients. Clinical trial information: 01709734.

 




Tokai + Qiagen/ Johns Hopkins: 液態檢體liquid biopsy (CTC) 強化 惡性攝護腺癌 賀爾蒙治療(Galeterone)精準度

Identification of a Companion Diagnostic (CDx) that Utilizes Circulating Tumor Cells (CTCs) to Detect an Androgen Receptor Splice Variant (AR-V7) in Metastatic Castrate Resistant Prostate Cancer (mCRPC) D. T. Dransfield1 , D Jacoby1 , K. Mamlouk1 , K Ferrante1 1 Tokai Pharmaceuticals, Cambridge, MA

Background: Antonarakis et al1 recently demonstrated that mCRPC patients with AR-V7 had worse clinical outcomes than patients without the splice variant (SV). Galeterone, a small molecule, disrupts androgen receptor (AR) signaling via multi-targeted pathways through degradation of AR protein, competitive antagonism of the AR, and selective inhibition of CYP17 lyase. AR-V7, a truncated form of the AR lacking the ligand-binding domain, remains constitutively active as a transcription factor. The detection of AR-V7 status in CTCs from mCRPC patients is associated with resistance to enzalutamide and abiraterone. In preclinical models, galeterone demonstrated activity against multiple AR aberrations, including AR-V7, ARv567es, AR-T878A, and AR-F876L. Given the encouraging results from the Phase 2 ARMOR2 trial in patients with C terminal loss, 2 further clinical research and validation is warranted. ARMOR3-SV, a Phase 3 trial comparing galeterone to enzalutamide in M1 AR-V7 SV patients is expected to be initiated in first half of 2015. Patients will be screened for CTCs, and presence of the SV will be confirmed prior to enrollment. Therefore, availability of a validated, accurate, rapid, quantitative, and universally applicable CDx assay performed in a central CLIA-certified laboratory for determining AR-V7+ status is critical to initiating the trial.

Method: Patients will be screened for CTCs and the presence of the AR-V7 will be confirmed prior to enrollment in the study. Development of a validated assay performed in a central CLIA-certified laboratory is crucial to the identification of M1 AR-V7+ CRPC patients fit for enrollment in ARMOR3-SV. Three methods are being evaluated. 1) Johns Hopkins (JHU): Isolation and enrichment of CTCs using immunomagnetic capture via epithelial and tumor-associated antigens (AdnaTest ProstateCancerSelect kit (AdnaGen) mRNA purification followed by qRT-PCR using custom primers for CTC confirmation and AR and AR-V7 determination (AdnaTest ProstateCancerDetect kit (AdnaGen)/JHU assay) 2) Epic Sciences & Circulating Tumor Cell Analysis (used in Tokai's ARMOR2): Immunofluorescence using Epic Sciences' N/C-terminal CTC Assay (IHC) to measure existence of splice variants via the presence of a truncated Cterminal domain. 3) Selective AR-V7 option under development (both IHC and RNA-FISH assays) MD Anderson Cancer Center (MDACC): Detection of C-terminal loss using immunohistochemistry methods to produce a ratio of N and C-terminus AR staining of CTCs in bone marrow AR-V7 specific antibody.

Results: CDx vendor selection criteria and recommendations are expected to be based on premarket approval experience, regulatory support, and technical expertise in the methodologies employed to identify AR-V7+ patients. This will include two steps: 1. CTC isolation/characterization and 2. methods to quantify AR-V7.  Conclusions: Choice of CDx assay to identify select mCRPC pts harboring a specific SV of the AR will be a key to enrollment strategy for ARMOR3-SV.

References:  Antonarakis ES et al. NEJM. 2014 Sep 11;371(11):1028-38., Taplin ME et al. ESMO 2014.

 

Galeterone shows activity in a variant form of castration-resistant prostate cancer November 18, 2014  The European CanCer Organisation (ECCO)  Results from a trial of the anti-cancer drug galeterone shows that it is successful in lowering prostate-specific antigen (PSA) levels in men with a form of prostate cancer that is resistant to treatment with hormone therapy (castration-resistant prostate cancer or CRPC). Results from a trial of the anti-cancer drug galeterone shows that it is successful in lowering prostate-specific antigen (PSA) levels in men with a form of prostate cancer that is resistant to treatment with hormone therapy (castration-resistant prostate cancer or CRPC). Associate professor Mary-Ellen Taplin, of the Dana-Farber Cancer Institute, Boston, USA, will tell the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, that galeterone was well tolerated by patients in the ARMOR2 trial, and also lowered PSA levels in a subset of men with CRPC that was resistant to other drugs that target the cancer, such as enzalutamide and abiraterone. "Recent data have shown that a variant of the androgen receptor called AR-V7, found in tumour cells circulating in the blood of patients with metastatic CRPC, predicted resistance to treatment with enzalutamide and abiraterone," she will say. "Indeed, we believe AR-V7 and other, related variants are a mechanism of resistance in this disease and patients who have them may have a poorer prognosis." Researchers believed that galeterone could be effective against CRPC because it disrupts the androgen receptor signalling pathways that are involved in the cancer, and preclinical work has shown it is active against the AR-V7 variant. Several clinical centres in the USA and Canada recruited four groups of men with CRPC to a phase II study to receive 2550mg of galeterone orally once a day: 22 men had CRPC that had not metastasised (spread) and had received no previous treatment; 39 men had metastatic CRPC and no previous treatment with abiraterone or enzalutamide; 37 and nine men had metastatic CRPC and had failed treatment with abiraterone and enzalutamide respectively. As well as evaluating PSA responses to the drug, the researchers also analysed levels of circulating tumour cells, including identifying whether or not they contained the AR-V7 variant. The AR-V7 variant is formed when an androgen receptor loses the end part of the receptor, called the C-terminal end; this is deleted due to an error in RNA processing in tumour cells, leaving only the beginning part of the receptor, the N-terminal end. The researchers concluded that patients with circulating tumour cells with more N-terminals than C-terminals had the androgen receptor variants. "We found that galeterone resulted in meaningful PSA declines in patients with metastatic CRPC, and imaging showed that the disease was stable or had responded to the drug," Prof Taplin will say. "Galeterone was safe, without any unexpected toxicity. We also detected circulating tumour cells, which were found in higher numbers in patients who had received more prior therapies. "In a subset of seven patients who had circulating tumour cells with a higher ratio of N-terminal compared to C-terminal androgen receptors and so were likely to have the AR-V7 variant, six had favourable PSA responses to galeterone. This suggests that the presence of AR-V7 in circulating tumour cells does not preclude response to galeterone as has been shown to be the case for abiraterone and enzalutamide." Among the group of men who had non-metastatic and metastatic disease who had not received prior treatment with abiraterone and enzalutamide, data for 60 were available for analysis. PSA levels declined by 30% or more (PSA30) in 50 out of 60 (83%) patients, of whom 42 (70%) went on to have declines of 50% or more (PSA50). Among patients who were resistant to abiraterone, 37 were available for evaluation; 13 out of 37 (35%) had any PSA decline. Among patients who were resistant to enzalutamide, nine were evaluable; five out of nine (56%) had any PSA decline. The presence of circulating tumour cells were evaluated in 71 patients and were found to be higher in 64 (90%) of the patients who had more advanced cancer that had failed more previous treatments. Galeterone will now be tested in a phase III trial in which patients with metastatic CRPC with the AR-V7 variant will be randomised to receive either galeterone or enzalutamide. The researchers will be looking to correlate AR-V7 with response to galeterone and to see what effect the drug has on the length of time patients survive without their disease progressing. "This phase III trial will be noteworthy for being the first prostate cancer trial to assess a biomarker, namely AR-V7 in circulating tumour cells, as a predictor of response at the same time as testing the efficacy of the drug," Prof Taplin will conclude. Professor Josep Tabernero, a member of the scientific committee for the EORTC-NCI-AACR Symposium and head of the medical oncology department at Vall d'Hebron University Hospital and director of the Vall d'Hebron Institute of Oncology, Barcelona, Spain, commented: "These are encouraging results, which show that galeterone has significant clinical activity in men with castration-resistant prostate cancer that fails to respond to other drugs. Understanding the biological and genetic basis to drug resistance and cancer progression has enabled researchers to identify and develop a targeted drug that may prove to be beneficial in this type of cancer, without causing unmanageable side-effects. We look forward to the results from the phase III trial with interest."

Constitutively Active AR-V7 Plays an Essential Role in the Development and Progression of Castration-Resistant Prostate Cancer  Scientific Reports 5, Article number: 7654  Received 28 September 2014 Accepted 01 December 2014 Published 07 January 2015 This study aimed to investigate the role of AR-V7 in development of castration-resistant prostate cancer (CRPC) and to determine whether the AR-V7 expression in CRPC tissues can predict cancer-specific survival. We enrolled 100 localized prostate cancer (PCa) (cohort 1), 104 newly diagnosed metastatic PCa (cohort 2), and 46 CRPC (cohort 3) patients treated at our institution. The expression of AR-V7 in PCa was assessed by immunohistochemistry. Cox regression models were used to evaluate the predictive role of all covariates for the development of CRPC in cohort 2 and for cancer-specific survival in cohort 3. Time to CRPC and cancer-specific survival curves were estimated using the Kaplan-Meier method. AR-V7 expression rate in cohort 3 was significantly elevated compared with other two cohorts (p < 0.001). Multivariate analysis revealed that AR-V7 was an independent predictive factor for CRPC development (HR = 2.627, p = 0.001) and for cancer specific survival (HR = 2.247, p = 0.033). Furthermore, the AR-V7 expression was associated with shorter survival in CRPC patients. Our results demonstrated protein AR-V7 levels in primary tumors can be used as a predictive marker for the development of CRPC and as a prognostic factor in CRPC patients. Therapy targeting AR-V7 may help prevent PCa progression and improve the prognosis of CRPC patients. Prostate cancer (PCa) is the most frequently diagnosed male malignancy in Western countries and represents the second leading cause of cancer-related death1. In China, the incidence of PCa, although lower than in developed countries, has increased remarkably over the past two decades partly attributed to increasing life expectancy, dietary changes and Westernized lifestyle. Furthermore, most newly diagnosed PCa patients already have metastatic disease because of a lack of PCa screening use prostate-specific antigen (PSA) and digital rectal examination in China. Androgen deprivation therapy remains the mainstay of advanced PCa management; however, almost all patients relapse and progress to castration-resistant prostate cancer (CRPC) within a median of 18–24 months, which is accompanied by poor outcome and high lethality. To date, the mechanisms underlying the transition to CRPC have not been fully clarified. Androgen and androgen receptors (ARs) play essential roles in the initiation and progression of PCa. Structurally, the human AR gene is composed of eight exons and encodes a multi-domain protein consisting of an N-terminal transactivation domain (NTD), a central DNA-binding domain (DBD), a hinge region, and a C-terminal ligand-binding domain (LBD). Recent results indicate that the LBD appears to be dispensable for AR transcriptional activity as its deletion leads to constitutive activation of AR transcription capability. Constitutively active, ligand-independent AR splice variants were proposed to be partly responsible for the development and growth of CRPC, irrespective of androgen level. Among more than 20 AR splice variants identified to date, AR-V7 is one of the most abundant and best characterized variants. The clinical relevance of AR-V7 has also been characterized in some respects. For instance, it was reported that increased transcription or protein AR-V7 levels has been detected in CRPC metastases and elevated expression of AR-V7 in PCa tissues is associated with biochemical recurrence and shorter survival. However, the predictive value of AR-V7 expression in primary PCa for the development of CRPC and its prognostic value for CRPC patients have not been well documented. In the current study, immunohistochemistry with an AR-V7 specific antibody, which is a feasible technique that is routinely used in clinical diagnosis, was employed to investigate the expression of AR-V7 in different stages of PCa (cohort 1, 100 localized PCa; cohort 2, 104 newly diagnosed metastatic PCa; cohort 3, 46 CRPC). We assessed the association between AR-V7 expression and patient characteristics and evaluated whether AR-V7 expression in primary tumors can predict the development of CRPC after adjusting for current prognostic factors, such as PSA nadir, time to PSA nadir, and PSA half-life (PSAHL) in cohort 2. Moreover, we determined whether AR-V7 expression in CRPC tissues can predict cancer-specific survival after transurethral resection of the prostate (TURP) in cohort 3 who underwent TURP due to dysuria at the CRPC stage.



Source: www.invitamed.com

太景許明珠: 股價表現相當委屈 !!

F*太景許明珠:新藥進度一切正常 營運看好 鉅亨網記者張旭宏 台北2015-05-0419:43  F*太景執行長許明珠表示,除口服劑型目標年底兩岸開賣,大陸針劑劑型三期臨床年底同步完成收案。(鉅亨網記者張旭宏攝)新藥廠F*太景(4157-TW)執行長許明珠表示,公司新藥進度一切正常,除口服劑型目標年底兩岸開賣,大陸針劑劑型三期臨床年底同步完成收案,加上美三期臨床可望攜手大廠,對於未來營運相當看好,因此對於股價的表現相當委屈! 許明珠指出,太景已經完成2個社區型肺炎與糖尿病足感染FDA二期的臨床試驗,並已取FDAQIDP認證與Fast Track待遇,可享10年專賣保護,公司先前曾提供台灣及大陸三期臨床試驗的數據,發函FDA詢問是否進入三期臨床試驗是否可避免重複某些進行臨床試驗,已獲FDA發函正面回覆,確可討論其可能性。許明珠進一步指出,先前FDA對社區型肺炎臨床試驗的收案限制已經在2014年初放寬,加上可免除若干臨床試驗的機會,將有利奈諾沙星美國三期臨床試驗的推展與授權合作的推展,目前台灣取得藥證,申請健保藥價中,衛福部已經正式發給奈諾沙星藥證,成為台灣研發第一個小分子新藥許可證,至於大陸部分,臨床數據審查部份已通過,現進行至cGMP查廠程序階段,中國藥證是與生產許可一起發給,生產主要由浙江集團新昌藥廠負責,兩岸目標都能在今年底前開賣。許明珠表示,因應兩岸病人的特殊性,針劑劑型單價約為口服劑型的8-10倍,市場規模也較大。該公司已在兩岸招募三期病人,其中大陸進度較快,預計總收案540人,今年可以達陣,台灣部分則規劃收案80人,兩地都將在完成三期臨床後,向主管機關申請藥證。至於幹細胞驅動劑布利沙福,許明珠進一步表示,布利沙福的安全性與幹細胞驅動效果相當突出,新增的臨床試驗證明,其用於多發性骨瘤病患的幹細胞動員臨床試驗,太景與德國Cellex簽署協議,將在德國德勒斯登大學附屬醫院,最多招募37位無法以G-CSF成功驅動出足夠幹細胞的捐贈者,測試布利沙福是否可以從異體造血幹細胞自願捐贈者身上驅動出足以進行移植的幹細胞,若成功將有機會申請孤兒藥上市。另外抗C肝藥物TG-2349,許明珠強調,TG-2349的臨床試驗已經證明具備高活性、廣譜性與簡便性的優點,尤其是其針對基因Ib型的病患特別有效,台灣和大陸超過50%C肝病人罹患基因型1b病毒,病患只要每日服用一劑TG-2349,連續服用3日,搭配連續4周干擾素加雷巴威林(Ribavirin)的療法後,在病患體內即偵測不到HCV病毒。許明珠進一步強調,TG-2349、長效干擾素及雷巴威林合併使用,治療慢性C型肝炎二期臨床試驗,已通過台灣TFDA核准在數家醫學中心進行臨床試驗外,已正式向中國CFDA提出申請以1.1類新藥資格進入臨床試驗,目前歐美雖有口服C肝藥物,部分療法以免搭配干擾素為訴求,然這些新型口服藥物,仍無法達到適用所有基因型C肝病毒均可免注射干擾素目標,各國健保無給付,因此只有極少數病人可以負擔新的口服劑型療法。若TG-2349療法通過臨床試驗,將可幫助亞洲中國佔全球C肝病患1/4,病患取得療效不遜甚至優於新上市口服藥物,且可望享有健保有給付,病患負擔成本較低,又可大幅縮短干擾素使用的藥物,提供醫界最理想的醫療選擇。

 

中國西門子 "再次"涉嫌 賄賂醫院

西門子醫療部門被曝在中國行賄1000家醫院 發佈時間:2015/5/4 0 記者:美南新聞 昨日有消息表示,西門子旗下醫療部門涉嫌在華賄賂醫院使用其高價醫療產品遭國家工商總局調查。北京商報記者就此多方諮詢西門子中國相關負責人,但電話均未接通。 昨日有消息表示,西門子旗下醫療部門涉嫌在華賄賂醫院使用其高價醫療產品遭國家工商總局調查。北京商報記者就此多方諮詢西門子中國相關負責人,但電話均未接通。消息稱,國家工商總局指控西門子公司及其經銷商通過免費提供醫療器材的方式,換取院方在此器材上獨家使用西門子公司開發的化學試劑,其行為違反了中國《反不正當競爭法》第8條,涉嫌賄賂。而此次被曝光的賄賂事件涉及包括驗血設備在內的多种醫療器材,涉案醫院多達1000家。據了解,國家工商總局從去年開始就對西門子旗下醫療部門涉嫌賄賂醫院使用其高價醫療產品一事展開調查,但該調查此前從未被外界知曉。這並非西門子醫療首次在華被曝行賄。美國司法部文件披露,20013-20079月間,為贏得基礎設施的合同,西門子花費了約14億美元用於在全球各地行賄,其中在華涉及商業賄賂的部門就包括西門子醫療,其支付約1440萬美元向5家中國醫院行賄,獲得近3億美元的醫療設備訂單。西門子為此向美國、德國政府支付了總額超13億美元的罰金。據了解,西門子1872年進入中國,涉足鐵路、能源和醫藥等多個領域。而西門子中國醫療部門提供的醫療設備主要包括實驗室診斷、助聽器和影像診斷與治療等,與美國通用電器(GE)、荷蘭飛利浦3家企業壟斷中國高端醫療設備70%的市場份額。去年,跨國醫藥公司葛蘭素史克在華行賄被處以30億元罰款,成為迄今為止中國針對藥企開出的最大罰單。

醣聯 乳癌抗體藥物 (Biosimilar) 達標認列收益 (三菱瓦斯) !!

醣聯攻抗乳癌藥 報捷 2015-05-05 04:54:58 經濟日報 記者黃文奇/台北報導台灣醣聯(4168)昨(4)日宣布,與長期合作夥伴日本三菱瓦斯化學近日已順利完成乳癌抗體藥物的生物相似藥第一階段開發,除認列相關業務收益外,雙方亦著手規劃下一階段的合作事宜。台灣醣聯與三菱瓦斯於去年10月簽訂該項生物相似藥開發協議,由醣聯進行生產細胞株及產程開發,並協同三菱瓦斯建立乳癌生物相似藥之品質相似性比較技術,包括糖鎖結構監控與蛋白質特性分析。醣聯昨日股價收55.2元,下跌1.4元。醣聯說,在這階段完成後,醣聯與三菱瓦斯已積極著手規劃下階段的合作事宜,除了將共同拓展與國際藥廠之合作,積極與具全球行銷通路之生技藥廠在生物相似藥上建立長期的合作夥伴關係,也將針對其他各類癌症及自體免疫疾病,續推動多項生物相似藥的研發計畫。

醣聯攜日夥伴完成乳癌生物相似藥第一階段開發 2015/05/04 17:19 MoneyDJ新聞 2主打抗醣質癌症新藥的醣聯(4168)(4)日表示,與長期合作夥伴日本三菱瓦斯化學(MITSUBISHI GAS CHEMICAL CO., INC.)近日已順利完成乳癌抗體藥物的生物相似藥第一階段開發,除將可認列相關業務收益外,雙方亦著手規劃下一階段的合作事宜。醣聯指出,與三菱瓦斯化學於去(2014)10月簽訂本項生物相似藥開發協議,由醣聯進行生產細胞株及產程開發,並協同三菱瓦斯化學建立乳癌生物相似藥之品質相似性比較技術,包括糖鎖結構監控與蛋白質特性分析。此項協議為雙方於生物相似藥長期合作的第一階段,所有工作已於本月份順利完成,而醣聯將可依所提供的服務認列相關業務收益。醣聯表示,在本階段完成後,與三菱瓦斯化學已積極著手規劃第二階段的合作事宜。一方面雙方將共同拓展與國際藥廠之合作,積極與具全球行銷通路之生技藥廠在生物相似藥上建立長期的合作夥伴關係。另一方面雙方也將針對其他各類癌症及自體免疫疾病,持續推動多項生物相似藥的新研發計畫。在對於生物相似藥開發至關重要的生產株製備、產程開發及糖鎖組成監控上,醣聯表示,公司均具備領先業界的全球獨特優勢;而即將增設的Non-GMP試量產工廠已進入細部規劃階段,並預計於明(2016)年正式運作。三菱瓦斯化學的蛋白質藥物專業量產能力,結合台灣醣聯既有的抗體藥物研發能量以及試量產工廠,將可從前端研發至後端量產,建立起完整且全球化的抗體事業版圖。醣聯表示,與三菱瓦斯化學將於下週共同參加513-15日在日本東京舉行的BIOtech Japan 2015展會,共同拓展抗體新藥及生物相似藥業務。此次展會預估將有超過15,000名業界人士參與。

基亞 歐朝銓: 積極併購&建立國際品牌!!!!

個股:基亞(3176)反向併購澳洲ProgenQ3完成,將啟動併購擴大檢驗試劑業務 財訊新聞 2015/05/04 12:17【財訊快報/何美如報導】基亞生技(3176)宣布反向併購澳洲上市公司Progen,將拿下Progen 71.73%的主導權,Progen並進行現金增資,將引進電子科技大廠,預計第三季會同步完成股份轉換及增資案,未來將積極啟動併購,擴大檢驗試劑業務;而Progen也將更名為TBG,開啟國內生技業首家在海外掛牌先例。基亞公告,將以百分之百持股的TBG(開曼),與持股19.7%Progen,以1:1的換股模式進行股份轉換,基亞將取得Progen 71.73%的過半股權,而Progen也同步進行現金增資,預定金額為800-1000萬澳元,將引進重量級電子科技大廠,屆時,基亞的持股仍會維持在五成以上。基亞副總經理歐朝銓表示,ProgenTBG合併後,Progen將更名為TBGTBG(開曼)旗下包括台灣TBG、廈門TBG(德必碁)和美國TBG,都會納入事業版圖,未來TBG的營運類別主力將以檢驗試劑為主。原本TBG的檢驗儀器主要是委外代工生產,藉由引進電子大廠,未來檢驗設備就能轉為自製。透過反向併購,可加速檢驗試劑進入資本市場,有利籌資。歐朝銓表示,完成籌資後,將積極啟動併購,橫向可強化產品線,垂直則可進行上下游整合。而選擇澳洲主要是著其能帶來先進國家的品牌形象,成為進入中國、東南亞等新興市場的最大利器。目前TBG已在廈門海滄區建置的德必碁(廈門)檢驗試廠去年已完工,今年開始進行試產及產品報批,預期2017年將開始有跳躍的業績表現。如果成功進行併購,明年或有機會見到業績的跳高表現。

基亞:媒體有關報導說明 鉅亨網新聞中心2015-05-04 11:52:05  第二條 第511.事實發生日:104/05/042.公司名稱:TBG Inc.(開曼)3.與公司關係[請輸入本公司或子公司]:本公司100%持股子公司4.相互持股比例:不適用5.傳播媒體名稱:工商時報 A56.報導內容:基亞力邀國內重磅級科技大廠入股,參與Progen公司現金增資…,也讓TBG從原本只生產檢驗試劑產品拓展至檢驗設備儀器的產出。7.發生緣由:說明工商時報10454日之報導8.因應措施:澄清說明媒體報導內容如下:(1)國內科技公司對Progen之投資及業務合作尚在評估階段。(2)TBG目前產品已包含檢驗試劑及檢驗設備,並非未來才拓展至檢驗設備儀器。9.其他應敘明事項:無。

國鼎Antroquinonol 獲FDA孤兒藥資格 (AMPK activation & mTOR inhibition ) !!

國鼎生技:本公司研發中血液腫瘤類之急性骨髓性白血病小分子新藥,獲得美國食品藥物管理局(FDA)核准通過孤兒藥資格 鉅亨網新聞中心2015-05-04 15:36:13  第三十四條 第421.事實發生日:104/05/04-->2.公司名稱:國鼎生技股份有限公司3.與公司關係(請輸入本公司或聯屬公司):本公司4.相互持股比例(若前項為本公司,請填不適用):不適用5.發生緣由:本公司新藥Antroquinonol獲得美國食品藥物管理局(FDA)通知,正式取得血液腫瘤類之急性骨髓性白血病孤兒藥資格認定(15-4763),經美國FDA認定為「孤兒藥」的藥品,除可獲得美國研究經費補助外,藥物主管機關更給予行政協助及市場專賣保護期等優惠措施。因為按孤兒藥程序進行臨床試驗,藉由FDA主動協助,將縮短取得藥證之時間。6.因應措施:7.其他應敘明事項:(1)研發新藥名稱或代號:GHAML(Antroquinonol)(2)用途:一種治療急性骨髓性白血病小分子新藥(3)預計進行之所有研發階段:口服劑型:二、三期臨床試驗(需與美國食品藥物管理局協商確認)FDA新藥查驗登記審查。(4)目前進行中之研發階段:A.提出申請/通過核准/不通過核准:本公司已獲得美國食品藥物管理局認證治療急性骨髓性白血病孤兒藥(15-4763)B.未通過目的事業主管機關許可者,公司所面臨之風險及因應措施:不適用C.已通過目的事業主管機關許可者,未來經營方向:本公司將依原先年度計畫,繼續研發完成急性骨髓性白血病之臨床試驗,獲得孤兒藥資格將適用美國的獎勵措施有效降低本公司研發支出。D.已投入之研發費用:已完成臨床前之相關試驗與一期臨床試驗。(5)將再進行之下一階段研發:A.預計完成時間:口服劑型臨床試驗規劃及範圍,需依據與美國食品藥物管理局討論審核結果而定,若一切順利完成,預計試驗完成時間約在106B.預計應負擔之義務:該小分子新藥係國鼎生技獨立研發,擁有100%專利權僅須完成相關臨床試驗。(6)新藥開發時程長、投入經費高且未保證一定能成功,此等可能使投資面臨風險,投資人應審慎判斷謹慎投資。



Antroquinonol displays anticancer potential against human hepatocellular carcinoma cells: a crucial role of AMPK and mTOR pathways.  Biochem Pharmacol. 2010 Jan 15;79(2):162-71.

Abstract 5'AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) are two serine/threonine protein kinases responsible for cellular energy homeostasis and translational control, respectively. Evidence suggests that these two kniases are potential targets for cancer chemotherapy against hepatocellular carcinoma (HCC). Antroquinonol that is isolated from Antrodia camphorate, a well-known Traditional Chinese Medicine for treatment of liver diseases, displayed effective anticancer activity against both HBV DNA-positive and -negative HCC cell lines. The rank order of potency against HCCs is HepG2>HepG2.2.15>Mahlavu>PLC/PRF/5>SK-Hep1>Hep3B. Antroquinonol completely abolished cell-cycle progression released from double-thymidine-block synchronization and caused a subsequent apoptosis. The data were supported by down-regulation and reduced nuclear translocation of G1-regulator proteins, including cyclin D1, cyclin E, Cdk4 and Cdk2. Further analysis showed that the mRNA expressions of the G1-regulator proteins were not modified by antroquinonol, indicating an inhibition of translational but not transcriptional levels. Antroquinonol induced the assembly of tuberous sclerosis complex (TSC)-1/TSC2, leading to the blockade of cellular protein synthesis through inhibition of protein phosphorylation including mTOR (Ser(2448)), p70(S6K) (Thr(421)/Ser(424) and Thr(389)) and 4E-BP1 (Thr(37)/Thr(46) and Thr(70)). Furthermore, the AMPK activity was elevated by antroquinonol. Compound C, a selective AMPK inhibitor, significantly reversed antroquinonol-mediated effects suggesting the crucial role of AMPK. Besides, the loss of mitochondrial membrane potential and depletion of mitochondrial content indicated the mitochondrial stress caused by antroquinonol. In summary, the data suggest that antroquinonol displays anticancer activity against HCCs through AMPK activation and inhibition of mTOR translational pathway, leading to G1 arrest of the cell-cycle and subsequent cell apoptosis.


Apple Watch心率偵測 非醫材 !

健康照護成穿戴式賣點 生物/環境感測器需求飆漲2015/5王智弘/廖昱如穿戴式應用點燃感測器新商機。Apple Watch上市後掀起穿戴式裝置健身及健康照護應用新風潮,吸引半導體廠不論老將新秀紛紛推出各種生物與環境感測器方案,其中,心率、大氣壓力、紫外線(UV)及氣體感測器更是群雄競逐焦點。蘋果迷引頸期盼的Apple Watch智慧手表,終於在423日正式開賣。由於蘋果僅開放網路訂購,因此實體店面並未如以往出現排隊人龍,不過仍有許多果粉前往「朝聖」,一睹Apple Watch的風采,並實際體驗其新奇功能。 Apple Watch加持 穿戴裝置出貨量飆升 對於Apple Watch的上市,市場研究機構多抱以正面的評價。Gartner研究總監Angela Mclntyre指出,現今全球有已有超過三億的iPhone使用者,這些都將是未來Apple Watch的潛在消費群;預期在Apple Watch正式開賣的推助下,全球智慧手表總出貨量可望由2014年的五百萬支,增長至2015年的四千萬支。另一家市調公司BI Intelligence亦認為,在果迷和高階消費者需求驅動下,Apple Watch首年出貨量將達一千五百萬支;而未來2年出貨量成長率亦分別高達65%43%。國際數據資訊(IDC)則預估,2015Apple Watch出貨量將可達一千五百九十萬支,占總體智慧手表出貨比例高達62%,為市場最大贏家;而此類可運行第三方應用程式(App)的智慧型穿戴裝置總出貨量,也可望在Apple Watch上市的激勵下,由2014年的四百二十萬件暴增至2015年的二千五百七十萬件,成長率高達511%(1)。儘管Apple Watch實際銷售表現仍待時間驗證,但不可否認的是,它的出現無疑已為穿戴式市場注入一股強勁發展動能,並將吸引更多業者跟進加入戰局,讓穿戴式市場更加蓬勃發展。

健康照護功能成亮點 穿戴式感測器需求揚 在新發售的Apple Watch眾多功能中,尤以心率偵測最受業界矚目,不少有意購買的消費者也對這項功能躍躍欲試。Apple Watch內建的心率感測器係基於光電容積脈波描記法(Photoplethysmography, PPG),其利用綠光發光二極體(LED)及紅外線光,再搭配可感光的光電二極體(Photodiode)來量測手腕中血液的光反射變化,藉此計算出心跳速率。根據蘋果官方指出,在一般使用狀況下,Apple Watch主要是用紅外線光以每10分鐘量測一次的頻率,來偵測使用者心跳,惟當紅外線光所測得的訊號不足以計算出心率時,系統則會自動切換成以綠光LED來進行感測。此外,當訊號過小時,該心率感測器也會藉由增強LED亮度和採樣率,來進行補償。事實上,早Apple Watch上市前,即有不少運動專用手表已開始導入這種光學感測式的心率偵測技術,如Mio AlphaTomTom皆有相關產品推出,並主打毋須另外配戴心跳帶的訴求,吸引運動愛好者。雖然傳統採用心電圖(Electrocardiogram, ECG)量測技術的心跳帶,心率偵測效果較為精準,但使用上並不方便,且有維護及衛生上的疑慮;而光學式心率感測方案不僅體積精巧、使用便利,量測精準度也已快速提升,並可符合消費性應用需求,遂成為穿戴式裝置製造商的設計新選擇,包括三星(Samsung)Galaxy Gear S、樂金(LG) G WatchMoto 360智慧手表皆已相繼採用,而蘋果Apple Watch的導入,更將助長這股設計潮流。市場研究機構IHS總監暨微機電系統(MEMS)與感測器資深首席分析師Jeremie Bouchaud表示,一如蘋果的iPhoneiPadApple Watch也將樹立智慧手表感測器規格的業界標準,並吸引其他多數的穿戴式產品製造商跟進採納,進而推升穿戴式裝置感測器出貨量在未來幾年快速成長。Bouchaud進一步分析,穿戴式裝置是感測器發展的溫床。隨著穿戴式產品中使用的感測器數量持續增加,相關產品市場規模也將同步擴大;而促成此一現象的原因,是穿戴式市場正由簡單功能的產品如計步器,朝向更複雜精密且多功能裝置發展,如智慧型手表。這些多功能智慧型產品,將採用更多感測器元件,以實現健康和活動監測,以及更先進的人機介面功能(1) 此外,智慧型手機品牌廠也已意識到對某些類型的感測器而言,穿戴式裝置是比手機更好的搭載平台。因此,IHS預期,諸如濕度計、心率計將逐漸由手機擴展至穿戴式裝置,如智慧手表,而這也將進一步刺激穿戴式感測器的出貨量。根據IHS統計預測,在健身和健康監測需求快速攀升的驅動下,穿戴式裝置使用的感測器出貨量,在2013?2019年將增長七倍,從2013年的六千七百萬顆,大幅躍升至2019年的四億六千六百萬顆,成長速度比穿戴式裝置市場本身更快。其中,智慧手表將是2015?2019年推動穿戴式感測器市場成長的最主要應用。IHS預估,2015年整體穿戴式感測器出貨量將成長一倍,其中用於智慧手表的感測器出貨量更將激增近600%

蘇清泉…專科護理師可協助住院醫師部分職務 ??!!

「醫生也是人!」衛福部推住院醫師每週工時不得超過66小時 Yuan 2015/05/05 09:05:005年前一位醫學中心外科住院醫師在開刀房倒下。病倒前他每天工作10小時以上,值班當日連續工時近36小時,再怎麼鐵打的身體,也禁不起這樣的長期操勞。 為改善醫生超時工作狀況,衛生福利部表示,從今年起,會將住院醫師每週工時不超過88小時納入醫院評鑑。中時報導,衛福部醫事司司長王宗曦表示,住院醫師每周工時狀況各科不一,大多在88小時左右,外科及婦產科則會到每周100小時,住院醫師長期都在爭取納入勞基法,但因工作內容有連續性性質,較無法納入。王宗曦指出,前兩年是試評,今年正試納入,且醫院一定要達到住院醫師每週工作不得超過88小時的目標。對此,醫勞盟理事長張志華則認為,衛福部根本無從稽查核對工時,且將醫院降級事關重大,質疑衛服部是否能強硬面對醫學中心。中央社報導,兼任中華民國醫師公會全國聯合會理事長蘇清泉表示,美國住院醫師每週工時標準是88小時,新加坡和香港則是66小時。目前衛福部設定88小時,但全聯會目標是23年間能降到66小時。為減少人力缺口,蘇表示增加專科護理師可協助住院醫師部分職務,目前現行專科護理師約4000人,希望未來能增至60008000人。對於醫生工作超時問題,中時採訪多為醫界大老,專長為婦科腫瘤的李發焜醫生就表示,1982年他擔任住院醫師,每3天輪一次全班,24小時要待命,來自病人、老師與學習上的壓力,真的很辛苦,但當年都普遍較「認命」,加上沒有超時工作的觀念,一名住院醫師要照顧好幾床患者,大家多半也苦苦的做、默默的做。刊登在蘋果的〈為什麼不讓醫師納入勞基法〉文章作者張肇烜醫師表示: 5年前一位醫學中心外科住院醫師在開刀房倒下。病倒前他每天工作10小時以上,值班當日連續工時近36小時,月工時高達360小時。再怎麼鐵打的身體,也禁不起這樣的長期操勞。他當時被診斷為心肌梗塞,雖經急救挽回生命,但腦部缺氧過久失去記憶。他忘了新婚妻子,也忘了才出生六個月的孩子,情節比電影《我的失憶女友》還更慘。 他的妻子說:「他現在的智力,比六歲的兒子還低,錢喚不回他的記憶,買不回我們家庭的和樂。」

張醫師語重心長寫道: 每一個人都應該受到保障,醫生也是人,為什麼政府要讓財團牽著鼻子走,不讓醫生納入勞基法?」住院醫師妻子的疑問,反映基層醫護人員的共同心聲。我們微聲盼望政府和大老能夠回應基層的聲音:「為什麼不讓醫師納入勞基法?」