(6446) 藥華醫藥的投資價值及願景 (第36頁)

AlanLiu0508
個人積分：270分
文章編號：70807908

270分

樓主

2018-11-07 12:38

馬刺迷您好, 一旦藥華藥 P1101 取得歐美 PV 一線用藥許可後, 會成為唯一 FDA/EMA 核准 PV 一線治療用藥。個人認為營收成長趨勢可參考JAKAFi 在 PV/ MF 市場滲透率如以下, 謝謝。

# PV 於 2014年被FDA 取得二線用藥核可, 25000名目標病患中, 滲透率達 20%
# MF 於 2011年被FDA 取得一線用藥核可, 16000名目標病患中, 滲透率達 40%

歐美病患人數部分, 擷取下圖為藥華藥公司簡報檔進行說明, 下表為大摩 2017年針對 PV市調分析, 若依照大摩推論數據回推, 美國PV病患治療人數為 116009人, 歐洲病患治療人數為 182681人, 和藥華藥簡報檔市調內容 PV 治療人數 119050人相當, 因此推論歐洲病患目標患者約為18-20萬人, 以上資訊供您參考。

馬刺迷

馬刺迷
個人積分：531分
文章編號：70812714

531分

352樓

2018-11-07 17:13

謝謝樓主大大，看來股價嚴重被低估。

AlanLiu0508

AlanLiu0508
個人積分：270分
文章編號：70970113

270分

樓主

2018-11-16 14:29

(6446)藥華藥合作夥伴AOP 公司獲維也納商會授予創新公司“Mercur獎”
Wirtschaftskammer Wien zeichnet innovativste Unternehmen mit "Mercur Award" aus
Die Preise gehen an: TCA Systems, AOP Orphan Pharmaceuticals AG, Lackner Ventures & Consulting GmbH, eguana GmbH und der Start-up Star an die usePAT GmbH.
https://news.wko.at/news/wien/Wirtschaftskammer-Wien-zeichnet-die-innovativsten-Unternehm.htm
時間：2018年11月14日9:30

Kategorie Life Sciences
Die AOP Orphan Pharmaceuticals AG mit „Ropeginterferon alfa‐2b“.

Die kleinen Patientenzahlen von seltenen Krankheiten (Orphan Diseases) erschweren die Entwicklung und Marktzulassung von Medikamenten. Die AOP Orphan verfügt über besondere Kompetenz und Marktpräsenz auf diesem Gebiet und ist als einer der europaweit führenden Anbieter der Branche ein österreichisches Vorzeigeunternehmen. Die Polycythaemia vera (Abk. PV) ist eine seltene, die myeloische Blutbildung im Knochenmark betreffende) Erkrankung, bei der eine abnorme Vermehrung von roten Blutzellen (Erythrozyten) vorliegt, ohne dass hierfür ein physiologischer Stimulus vorhanden ist. Die Substanz Ropeginterferon alfa‐2b zeigte vielversprechende Erfolge in klinischen Studien und wurde daher im Februar 2017 bei der europäischen Behörde zur Zulassung als „Orphan Drug“ eingereicht. Der Abschluss des Verfahrens wird für Ende dieses Jahres erwartet.

類別：生命科學
AOP Orphan Pharmaceuticals AG 與 (6446)藥華藥新一代長效型干擾素“Ropeginterferon alfa-2b”。

因少數孤兒藥病患使得藥物的研發和市場認同更加困難。(6446)藥華藥合作夥伴AOP Orphan在該領域擁有特殊的能力和市場地位，是奧地利領先的歐洲指標公司之一。PV是一種罕見疾病，它影響骨髓中的骨髓血液形成，其中紅血球的異常增殖沒有任何生理刺激。(6446)藥華藥新一代長效型干擾素“Ropeginterferon alfa-2b”已顯示出優異的臨床試驗結果，因此於2017年2月申請歐洲孤兒藥藥證批准，預計今年年底完成審查過程。

Über den Mercur
Der Mercur ist der Innovationspreis der Wirtschaftskammer Wien und wird jährlich vergeben – 2018 bereits zum 31. Mal. Ziel ist, das Innovationspotenzial der Wiener Unternehmen aufzuzeigen und zu stärken. Der Mercur ist kein Ideenwettbewerb. Die eingereichten Projekte müssen bereits am Markt sein oder eine wirtschaftliche Verwertung unmittelbar und nachweislich bevorstehen.
Die Auszeichnung wird in den Kategorien Kreativität, Life Science, Green Economy sowie Informations- und Kommunikationstechnologie/Technik verliehen. Zudem wird der „Startup-Star Vienna“ vergeben. Das Industriewissenschaftliche Institut bewertet die eingereichten Projekte.

關於Mercur
Mercur是維也納經濟商會的創新獎，每年頒發一次，2018年為第31次。目標是突顯和加強維也納公司的創新潛力。
Mercur並非是創意競賽。提出申請的項目必須已經在市場上或直接和明顯地即將有商業模式開發。該獎項分為創意，生命科學，綠色經濟和通信技術。此外，還將頒發工業科學研究所評估提交申請的項目“創業之星維也納”獎。

馬刺迷

馬刺迷
個人積分：531分
文章編號：70976600

531分

354樓

2018-11-16 22:17

有藥證審查的結果了嗎？

AlanLiu0508

AlanLiu0508
個人積分：270分
文章編號：70977398

270分

樓主

2018-11-16 23:16

馬刺迷您好, 截至目前 11月所公告CHMP 會議結果尚未提供藥華藥新一代干擾素 P1101 審查會議結果, 如網頁描述,

"請注意，並非所有審查內容都會同時發布, 本頁面在取得新的藥物審查資料時會立即更新。請使用者定期更新此頁面。"
(Please note that not all documents associated with this page are published at the same time. This page is updated with new documents as soon as they become available. Therefore, users are asked to check the page regularly.)

建議接下來可定期追蹤 CHMP 11月會議結果連結, 會議連結如下請參考, 謝謝。

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 12-15 November 2018
https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-12-15-november-2018

oist

oist
個人積分：86分
文章編號：71024465

86分

356樓

2018-11-20 9:45

AOP 送回 D180 回覆後，是需要經由程序上的確認，才會開始往下計時。

Ropeg 11月列入 CHMP 的 SAG report 口頭報告，就是之前公司說的"專家會議"，須等會議結果出來，才開始由 D180 往下計時至 D210 。所以, 這時候的時間是停在 D180 ，當然 11 月的 CHMP 會議就不可能會有評價。

開完專家會議，經由 CHMP 通知，若 AOP 想補充資料，可以申請 Stop clock ，若不補充資料就會列入 12 月的
Initial Application Opinions ，由 CHMP 做出評價。

專家會議後，也有自行撤件( withdrawal )，這通常都是與 CHMP 溝通後，仍可能給負面評價而自行撤件。

會撤件或給負面評價，通常都是"副作用"與"療效"上的疑慮。

另外，有網友提到，仿單上會提到 off label use 的狀況或說明，這是不可能的事，不要想太多了。

以上供參考。

To be or not to be.

AlanLiu0508

AlanLiu0508
個人積分：270分
文章編號：71133981

270分

樓主

2018-11-27 10:11

節錄翻譯本期刊 (6446) 藥華藥新一代干擾素P1101 相關內容, 供各位投資先進們參考。

Clinical Advances in Hematology & Oncology
血液學和腫瘤學的臨床進展
November 2018 - Volume 16, Issue 11
2018年11月 – 第11期，第16卷

Novel Therapeutic Approaches in Polycythemia Vera
PV 的新型治療方法
www.hematologyandoncology.net/archives/november-2018/novel-therapeutic-approaches-in-polycythemia-vera/

Abstract:

Polycythemia vera (PV) is the most common Philadelphia chromosome–negative myeloproliferative neoplasm. Whereas low-risk patients are treated with aspirin and phlebotomy, high-risk patients receive cytoreductive therapy, which most commonly consists of hydroxyurea in the United States. Concerns about the long-term safety of hydroxyurea, as well as a desire for more efficacious and targeted therapy, have led to the development of novel therapies for high-risk patients with PV. Pegylated interferon (IFN) has shown promise in phase 2 studies of PV, and preliminary data from ongoing phase 3 studies suggest noninferiority as a frontline therapy. Efficient count control, tolerability, and even molecular responses as a salvage therapy have been demonstrated. Ropeginterferon-α-2b, a monopegylated IFN with a longer half-life and less frequent dose interval compared with recombinant or pegylated IFN, is an impressive agent in development. Ruxolitinib has a proven role as second-line therapy for PV, but an ongoing trial combining ruxolitinib and IFN as salvage therapy is under way. Early-phase clinical trials have also suggested that MDM2 inhibitors such as idasanutlin and histone deacetylase inhibitors should continue in their development. If these novel agents are able to modify the natural history of PV, the treatment paradigm in newly diagnosed patients will evolve from risk-adapted or reactive treatment toward early interventions.

摘要：
PV是最常見的費城染色體陰性骨髓增生性腫瘤。低風險病患治療方式為阿司匹林和放血，高風險性病患接受細胞減滅治療，其中美國最常見的治療方式是HU。由於對HU的長期安全性的考量，以及對更直接療程的需求，導致各種針對PV高風險病患新療法持續被開發。長效型干擾素（IFN）在PV的臨床二期研究中已經展示出療效，目前一線療法中正在進行的臨床三期研究的初步數據顯示出非劣性；包含血液濃度控制、耐受性，甚至分子反應。與重組干擾素或長效型干擾素相比，新一代長效型干擾素Ropeginterferon-α-2b是一種單一化合物干擾素，具有更長的半衰期和更低的注射周期，是一種令人印象深刻的治療方式。
JAKAFi已被證明可作為PV的二線治療，但目前正在進行將JAKAFi和干擾素的合併療法。早期臨床試驗也表明，MDM2抑制劑如idasanutlin和HDAC抑制劑也應該持續研發。如果這些新型藥物能夠改變PV病史，那麼新診斷病患的治療方試將從這些風險適應性治療轉變為早期預防。

Ropeginterferon-alfa-2b 新一代長效型干擾素P1101

Ropeginterferon-α-2b is a novel IFN with a longer half-life compared with recombinant or pegylated IFN, which allows administration every 2 weeks (or monthly during long-term maintenance). This agent is currently undergoing clinical testing.14-16 Ropeginterferon α-2b was first investigated in both newly diagnosed and previously treated PV patients. A phase 1 dose-escalation study of 25 patients was performed that determined the maximum tolerated dose (540 μg of ropeginterferon α-2b every 2 weeks) using a 3+3 dose-escalation protocol. For the second phase of the trial, 26 additional patients were enrolled, for a total of 51 patients. These patients were followed prospectively while receiving a mean dose of 263 μg of ropeginterferon α-2b every 2 weeks.14 Dosing was based on efficacy and long-term tolerability. After 10 weeks of treatment, 26% of patients had a CHR and 49% had a PHR. These rates of hematologic response appeared relatively constant for up to 146 weeks of follow-up, with the best response rates occurring after a median of 82 weeks, when 47% of patients had a CHR. However, it should be noted that the number of patients analyzed dropped considerably as the length of follow-up increased, with data from only 9 patients being available at 146 weeks.14 Molecular response was also measured, and the median JAK2 V617F allele burden decreased from 41% at enrollment to 25% after 50 weeks of follow-up. Twenty percent of patients discontinued therapy owing to treatment toxicity, and 88% of patients experienced adverse events.14

與重組干擾素或長效型干擾素相比，新一代長效型干擾素Ropeginterferon-α-2b是一種具有更長半衰期的新型干擾素，允許每2週（或在長期治療期間每月）注射一針。該藥物目前正在進行臨床試驗。首先臨床一期針對25名在新診斷和先前治療過的PV病患中進行了劑量遞增性研究，其使用3 + 3劑量遞增方案確定最大耐受劑量（每2週540 μg P1101）。試驗第二階段額外招募了另外26名病患，共51名病患，隨機對這些病患進行追蹤，同時每2週接受平均劑量263μg的Ropeginterferon-α-2b，劑量基於療效和長期耐受度。治療10週後，26％的病患達到完全血液學反應（CHR），49％的病患達到部分血液學反應（PHR）。這些血液學反應率在長達146週的追蹤中仍持續穩定，在為期中位數82週時出現最佳反應率，當時47％的病患達到完全血液學反應（CHR）。然而隨著觀察時間越長，進行分析的病患數字大幅下降，到146周時僅剩9名病患的數據可取得。分子反應也在測量範圍內，JAK2 V617F等位基因負擔中位數從一開始的41％降到觀察50週後的25％。 20％的病患因治療的毒性而中斷治療，88％的病患出現不良反應。

These results led to the PROUD-PV study (Pegylated Interferon Alpha-2b Versus Hydroxyurea in Polycythemia Vera), a multicenter randomized controlled trial comparing ropeginterferon α-2b with HU in patients who either were treatment-naive or had prior treatment with HU and were neither intolerant of the agent nor complete hematologic responders, with a maximum cumulative treatment of 3 years.15 The trial enrolled 254 patients with PV. The primary endpoint was noninferiority of CHR at 12 months, and a secondary endpoint was the rate of molecular response (MR). Based on the intention-to-treat analysis, CHR was achieved by 43.1% of patients randomly assigned to ropeginterferon α-2b and 45.6% of patients assigned to HU, meeting the criteria for noninferiority.15 Molecular analysis of 13 patients, 5 of whom received ropeginterferon and 8 of whom received HU, provided information regarding MR. The median JAK2 V617F allele burden decreased from 39.4% to 13.8% in patients treated with ropeginterferon and decreased from 46.5% to 33.2% in those who received HU.16
這些結果導向了PROUD-PV研究的進行，這是一項多中心隨機對照試驗，比較了新一代長效型干擾素P1101與HU用來治療從未接受治療的PV病患亦或不耐受HU治療也沒產生完全血液學反應者，累積最長治療時間為3年。試驗招募了254例PV病患。主要療效指標終點是12個月時完全血液學反應呈現非劣性，次要療效終點是分子反應率（MR）。根據意向治療分析(ITT)，隨機分配至新一代長效型干擾素P1101的病患中有43.1％達到完全血液學反應（CHR），而分配至HU的病患中則有45.6％，符合非劣性標準。13名病患進行分子反應分析，其中5名病患使用P1101進行治療，其他8名病患使用HU。使用P1101治療的病患JAK2 V617F等位基因負擔中位數從39.4％降至13.8％，而接受HU治療的病患則從46.5％降至33.2％。

After 12 months, patients from the PROUD-PV study were rolled over into the CONTI-PV study (AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study). Ninety-five patients continued to receive ropeginterferon and 76 patients continued to receive HU or best available therapy (BAT) at the investigators’ discretion. An interim analysis that included 24 months of follow-up was presented at the 2017 American Society of Hematology annual meeting.17 A total of 88 patients taking ropeg-interferon and 73 patients taking HU/BAT completed 24 months of therapy, with a comparable dropout rate between the groups of 8.4% and 6.6%, respectively. The rate of CHR was significantly higher in patients receiving ropeginterferon (70.5%) than in those receiving HU/BAT (49.3%). The composite endpoint of CHR and symptom improvement occurred in 49.5% of patients receiving ropeginterferon compared with 36.6% for those receiving HU/BAT, but this was not a statistically significant difference. Further, a partial MR occurred in 69.6% of patients receiving ropeginterferon and 28.6% of those receiving HU/BAT. Lastly, a comparable number of patients (70.1% for ropeginterferon and 77.2% for HU/BAT) experienced treatment-related adverse events. A formal symptom assessment tool, such as MPN-SAF, was not used in this study. Although this trial is ongoing, this interim analysis suggests that ropeginterferon α-2b may prove to be a more efficacious and safe treatment for PV compared with HU.
12個月後，來自PROUD-PV臨床試驗的病患持續CONTI-PV研究。 95名病患持續使用P1101進行治療，76名病患繼續接受HU或BAT治療由研究人員自行決定。 2017年美國血液學會年度會議上提供了24個月的期中分析。共有88名使用P1101進行治療的病患和73名使用HU / BAT進行治療的病患完成了24個月療程，中斷治療的比率分別為8.4％和6.6％。P1101組的病患完全血液學反應（CHR）（70.5％）顯著高於HU / BAT組（49.3％）。 CHR和症狀改善的複合終點上，P1101組為49.5%，而HU / BAT組為36.6％，但這並沒有在統計學上呈現顯著差異。此外，P1101組中有69.6％產生部分分子反應，HU / BAT組中則為28.6％。最後，不少病患（P1101組為70.1％，HU / BAT組為77.2％）經歷了與治療相關的不良反應。該研究並未採用正式的症狀評估工具(MPN-SAF)。雖然該試驗仍在進行中，但這項中期分析顯示出，與HU相比，P1101也許被證明是一種更有效和安全的PV治療方法。

Combination Therapy With Interferon and Ruxolitinib
干擾素和JAKAFi 的合併療法
Ruxolitinib is also currently being studied in combination with peg-IFN in patients with MPNs in the COMBI study (Safety and Efficacy of Combination Therapy of Interferon‐α2 and Ruxolitinib in Polycythemia Vera and Myelofibrosis).33 Thirty-two patients with PV were enrolled, most of whom were intolerant of IFN previously. The primary endpoint was the rate of CR or PR at 12 and 24 months. Evidence of active disease was required. Patients were treated with peg-IFN-α-2a at 45 μg per week or peg-IFN2b at 35 μg per week, plus ruxolitinib at 20 mg twice daily. Nine percent of patients with PV obtained a PR, and 44% experienced a CHR. The JAK2 V617F allele burden decreased from a median of 47% to 23.5% by 12 months. Eighty-one percent of patients with PV remained on treatment by month 12. Twenty percent of patients had to discontinue therapy owing to adverse events. Hematologic toxicity was most common, and included grade 1 or 2 anemia in 56% of patients, grade 1 or 2 leukopenia in 50% of patients, and grade 1 or 2 thrombocytopenia in 28% of patients. The toxicity was in part attributed to a higher dose of ruxolitinib than is typically used in PV.33 The study investigators wrote that they envision further development of this combination, but at lower doses.
COMBI臨床試驗中，JAKAFi目前正結合長效型干擾素合併療法在MPN病患中進行研究。該研究招募了32名PV病患，其中大多數病患先前之前不耐受干擾素。主要終點是12個月和24個月的完全血液學反應或部分血液學反應，需要疾病存在的證據。病患使用每週45μg的長效型干擾素或每週35μg的長效型干擾素加上每天兩次20mg的JAKAFi進行治療。 PV病患中有9％產生部分血液學反應，44％產生完全血液學反應。 JAK2 V617F等位基因負荷在12個月內從中位數47％降至23.5％。
81％的PV病患在12個月的治療後仍接受治療。20％的病患因不良反應不得不中斷治療。
血液學毒性最常見，56％的病患出現1級或2級貧血，50％的病患為1級或2級白血球數量減少，28％的病患為1級或2級血小板減少。毒性部分歸因於給比一般PV較高劑量的JAKAFi。研究調查人員打算持續針對合併療法進行研究，但須提供較低劑量。

Conclusion
結論
Many therapies are currently under development for high-risk patients with PV. Peg-IFN has proven efficacy in the treatment of patients with PV. Preliminary results from ongoing head-to-head trials suggest that IFN therapy is noninferior to HU as a frontline therapy for PV. Emerging data also suggest efficacy in a salvage setting. Although trials are still ongoing, ropeginterferon α-2b, with its longer half-life compared with standard IFNs and resultant less frequent dose interval, is a highly promising IFN that is in development. Ruxolitinib has an established role as a second-line therapy for patients with PV who are resistant to or intolerant of HU. Though only a small number of patients have been studied and longer follow-up time is needed, a combination of ruxolitinib and IFN is intriguing. Early-phase clinical trials have shown a signal for potential efficacy with MDM2 inhibitors. Finally, HDAC inhibitors have promise as salvage therapy, but their role is still investigational and remains to be defined. Provided that continued clinical investigation is able to confirm the efficacy of the novel PV therapies discussed here, the treatment paradigm can finally shift away from nonselective, restrictive/reactive treatments toward early targeted interventions in newly diagnosed patients, with an aim to modify the natural history of this chronic myeloid neoplasm.
許多療法正在針對高風險PV病患進行研究。長效型干擾素已被證實在PV病患的治療中有效。正在進行的試驗初步結果顯示出，干擾素和HU在PV一線用藥治療上呈現非劣性。新出示的數據也顯示出療效。雖然試驗仍在進行中，但是與標準干擾素相比具有更長半衰期並且較低頻率的注射周期的新一代長效型干擾素(P1101) 是一種非常具有前景的干擾素，目前在開發階段。
JAKAFi在HU無效或不耐受的PV病患的二線治療中有實際作用。雖然只有少數病患進行研究，仍需要更長時間的追蹤，但是JAKAFi和干擾素的組合很有吸引力。
早期臨床試驗顯示MDM2抑制劑具有潛在療效；HDAC抑制劑有望作為治療選項，但它們的作用仍待持續研究並且定義清楚。如果這邊討論的這些持續性的臨床研究能夠證實PV治療上的療效, 那麼新診斷出的PV病患將從選擇性、限制性的治療方向轉變為早期的靶向治療以改變病史。