PHARMAESSENTIA – On the road to product launch
www.forbes.com/custom/2019/07/15/taiwan-a-bright-future/#pharmaessentia-on-the-road-to-product-launch
(6446) 藥華醫藥正在產品發表的道路上
Since 1984, the number of biotechnology companies listed on the Taiwan Stock Exchange has gone from precisely zero to more than 100, with a combined value of US$25 billion.
自1984年以來，在台灣證券交易所上市的生技公司數量從零到超過100間，總價值達到250億美元。
The government in Taipei can take some of the credit for this after identifying the industry as the next Big Thing to promote after its success in establishing the island as a center of excellence and innovation for the semiconductor manufacturing sector; but so too can the cohort of scientists and entrepreneurs who have provided the skill and the commercial acumen that has seen Taiwan established as an engine room for an industry that is not just making a significant contribution to the island’s economy but is also helping improve the health and the quality of life of millions of people around the world.
台灣政府在成功將台灣打造成半導體製造的卓越和創新中心之後，將生技產業確定為下一個大型推廣產業。這些擁有技術和商業頭腦的科學家和企業家也是如此，他們已經將台灣視為產業的發展引擎，生技產業不僅對台灣的經濟做出了重大貢獻，而且還有助於改善健康狀況以及全世界數百萬人的生活品質。
One of the Taiwanese diaspora to respond to Taipei’s clarion call was PharmaEssentia’s CEO Ko-Chung Lin. In 2003, he joined a team of Taiwanese-American executives and high-ranking scientists from leading U.S. biotechnology and pharmaceutical companies who decided to come back home to launch a company dedicated to the development of drugs designed to treat myeloproliferative neoplasms (MPNs), such as polycythemia vera (PV), essential thrombocythemia (ET), myeloid fibrosis (MF) and chronic myeloid leukemia (CML), as well as hepatitis and cancer.
其中一位帶動生技產業號角的是從海外回台的藥華藥執行長林國鐘博士。2003年，他與一群美國首屈一指的生技公司台灣裔高階主管和高級科學家團隊，決定回國創辦一家專門研發治療骨髓增生性腫瘤（MPNs）的藥物的公司，這類疾病包含真性紅血球增多症(PV），原發性血小板增多症（ET），骨髓纖維化（MF）和慢性骨髓細胞白血病（CML），以及肝炎和癌症。
“I chose to set up the company here rather than in the U.S. because Taiwan is probably the best place in the world in which to raise capital for a biotech company,” Ko-Chung explains. It was the right call. The company’s 2016 IPO raised more than US$100 million and immediately propelled PharmaEssentia into the top half of Taiwan’s league of biotech companies.
林國鐘博士說“我選擇在這裡創辦公司而不是在美國，主要是因為台灣可能是世界上生技公司籌資的最佳地點”。這是正確的決定。該公司2016年於首次ＩＰＯ募資超過1億美元，迅速將藥華醫藥推向台灣生技公司的領先地位。
That could be just the beginning. Earlier this year, the European Commission (EC) announced that it had given marketing approval for Besremi® (ropeginterferon alfa-2b). Developed in conjunction with AOP Orphan Pharmaceuticals, Besremi® is indicated as monotherapy in adults for the treatment of polycythemia vera without splenomegaly. Following the EC ruling, it is now the only such treatment available to PV sufferers across most of Europe.
那僅僅只是個開始。今年年初，歐洲委員會（EC）宣布已經批准了Besremi®（ropeginterferon alfa-2b）的新藥上市許可。 Besremi®與AOP Orphan Pharmaceuticals共同開發，可作為適用於成人單方治療，用於治療無脾臟腫大症狀的紅血球增生症。在歐洲委員會（EC）決議之後，它現在是歐洲大部分地區PV病患唯一可用的治療方法。
For Ko-Chung, it makes all the blood, sweat and occasional tear that he and his colleagues have shed on the way worthwhile. “We have conceptualized an idea and turned it into a reality,” he beams. “I have been a scientist for 40 years and it is the dream of anybody in my profession to find themselves in this position. It is very rewarding.”
對於林國鐘博士而言，這是他和他的同事們一路上用汗水、血淚取得的成就。 “我們已經將一個概念化的想法化為現實，”他提到。 “我40年來一直是一名科學家，我們這個職業，每個人都有著夢想。這實在令人鼓舞。“
Ko-Chung is only too aware, however, that the hard work has only just begun. “The challenge for us now is to explain to our investors that even having met the milestone of gaining EC approval for Besremi®, making money from it will not happen overnight, and we still need their support to carry us through the initial marketing stages. Two other firms in this sector found themselves in a similarly great position of having an approved drug with a lot of potential recently, but their shares plunged because their cashflow did not immediately rise. I learned a lot from their experiences, and we try to give our shareholders as much precise information as possible so that they understand our plan and potential.”
然而，林國鐘博士意識到，艱苦的工作才剛剛開始。 “我們現在面臨的挑戰是如何向我們的投資者解釋，即使已經取得歐洲委員會（EC）批准Besremi®新藥許可的里程碑，也不會在一夜之間賺錢，我們仍需要投資者的支持才能帶領我們度過最初的銷售階段。另外兩家生技公司最近也是一樣的狀況，在有潛力的藥物取得銷售許可後，因為他們的現金流沒有立即攀升，導致股價暴跌。我從他們的經歷中學到了很多東西，我們努力為股東盡可能提供準確的資訊，以便他們了解我們的計劃和潛力。“
The next step for PharmaEssentia is to strengthen its U.S. presence. The company already has a second-line PV reference drug (given to patients after they have been previously treated with another drug) and is looking for FDA approval to be classified as a first-line option. According to Ko-Chung, the PharmaEssentia’s product has the potential to treat 4.5 times more patients than the current drug of official choice.
藥華醫藥下一步是強化在美國的布局。該公司已經擁有PV二線用藥的用藥JAKAFi上市參考（該藥為於病患之前曾接受過其他藥物治療後給予），目前正在尋求FDA批准為一線用藥。根據林國鐘博士的說法，藥華藥的新藥病患群比官方批准的藥物治療病患多出4.5倍。
With the assistance of its office in Boston, the company is going to expand indication for BESREMI® to include ET and is currently in talks with the FDA to conduct a Phase 3 clinical trial. Ko-Chung expects development and rollout to take another three years or so, giving it access to a segment of the healthcare worth between US$5 billion and US$10 billion. It will also be marketed in Taiwan, Japan, Korea and China.
在波士頓辦事處的協助下，該公司將擴大BESREMI®的適應症範圍包括ET，目前血小板增多症(ET)正在與FDA進行討論以進行臨床三期試驗。 林國鐘博士預計研發到銷售推廣需要三年左右的時間，這市場潛力有50億至100億美金的價值。該藥物也將在台灣、日本、韓國和中國銷售。
Another drug for Hepatitis B patients is also in the later stages of development and more innovations and discoveries will surely follow. “We are humble and we continue to learn. This is why our success rate in discovering new drugs is so high,” says Ko-Chung.
Ｂ型肝炎病患的藥物研發也進展到最後階段，在此之後肯定會有更多的創新和發明。“我們很謙虛且持續學習。這就是為什麼我們研發新藥的成功率如此之高，“林國鐘博士說。
日期：2019/8/1
【財訊快報／記者何美如報導】
藥華藥( 6446 )宣布，創新生物藥百斯瑞明（Ropeginterferon alfa-2b，P1101）7月31日向台灣衛福部食藥署（TFDA）遞交真性紅血球增生疾病（PV）的藥證申請文件，在新藥查登優先審查認定助攻下，有機會在明年再取得台灣PV藥證。
百斯瑞明已於7月31日向TFDA成功遞交PV藥證申請文件，由於藥華藥先前已取得新藥查驗登記優先審查認定，審查時間可由360天大幅縮短為240天，估計最快可於2020年Q2取得TFDA之PV藥證，成為繼今年2月取得第一張歐盟PV藥證後的第二張藥證。
藥華藥表示，為達藥品生產一貫化作業，未來供銷亞洲地區的百斯瑞明會在台中廠生產原料藥，並進行針劑產品充填。針劑廠已順利完成廠房與設備的確效作業，並於2018年12月起執行三批製程確效，在PV藥證申請同時，相關針劑廠的查廠準備工作也已就緒，並可依TFDA要求進行查廠作業，取得商業化GMP/ GDP認證後，將供應亞洲地區藥品需求，初期先供應台灣、日本、大陸、韓國。
真性紅血球增生症（PV），目前在台灣並沒有詳細的流行病學數據。根據文獻綜述顯示，歐盟的PV盛行率是每十萬人中有5至30人。日本的PV盛行率是每十萬人中有16人，相較於美國每十萬人有46人仍偏低。臺灣PV患者的現行治療方法包括放血、低劑量阿斯匹靈及愛治膠囊（Hydroxyurea）。
PV初期的症狀包含疲勞、活動力下降、注意力不集中、難以入睡、皮膚搔癢等，並沒有明顯特徵，因此病人可能忽略了這些是疾病的症狀，而未尋求醫療協助。此外，根據美國Director of University of Texas Health Care Cancer Center in San Antonio, MD Anderson Cancer Center (MDAC) 的權威教授Dr. Ruben Mesa等人的研究顯示，PV該有的嚴重症狀（腹部疼痛／不適、血栓、頭暈）與病患陳述之嚴重症狀不一致（疲勞、活動力下降等），如此認知上的落差，亦可能是導致延緩診斷的原因之一。
2019年8月2日
工商時報【杜蕙蓉╱台北報導】
藥華藥（6446）宣布，治療真性紅血球增生疾病（PV）的創新生物藥百斯瑞明（Ropeginterferon alfa－2b，P1101），已向台灣食藥署（TFDA）遞件交申請文件，估計最快2020年第二季取得藥證，台灣將成亞洲PV病患第一個受惠國。
藥華藥表示，為達藥品生產一貫化作業，未來供銷亞洲地區的百斯瑞明R，將在台中廠生產原料藥，並進行針劑產品充填。台中廠已於2018年12月起執行三批製程確效，目前規畫先以供應台灣、日本、大陸、韓國為主。
百斯瑞明R新藥先前已獲TFDA優先審查認定，審查時間可由360天大幅縮短為240天，2020年第二季取證機會高，這是藥華藥開發的新藥在2019年2月取得歐盟藥證後，再傳出的藥證利多。
真性紅血球增生症（PV），目前在台灣並沒有詳細的流行病學數據，須藉其他國家的研究結果來預估台灣現況。據文獻綜述顯示，歐盟的PV盛行率是每十萬人中有5至30人，參考亞洲人之數據，日本PV盛行率是每十萬人中有16人，較美國每十萬人有46人仍偏低。臺灣PV患者的現行治療方法包括放血、低劑量阿斯匹靈及愛治膠囊（Hydroxyurea）。
分享病友團體 MPN Interferon Forum - (Myeloproliferative Neoplasm) 奧地利病患取得 (6446) 藥華藥新一代干擾素 Besremi 後相關討論，翻譯如下供各位投資先進參考，謝謝。
Ida Idic
Hi everyone, I have yesterday begin with therapy Besremi. Very will I tolerate medication.
Hi 各位, 我昨天開始(6446) 藥華藥新一代干擾素 Besremi 的治療, 藥物耐受度非常好。
Mecky Rennebaum-González
I‘m still waiting - but it may take a while before Besremi becomes available in Switzerland.
我還在等待，但在(6446) 藥華藥新一代干擾素 Besremi在瑞士上市之前可能還需要一段時間。
Ida Idic
Mecky Rennebaum-González I believe this month come in Switzerland.
Mecky Rennebaum-González，我相信這個月Besremi會進到瑞士。
Katarzyna Rola：
Where are you from and how often do you take it?
你來自哪裡以及你多久使用一次？
Ida Idic：
Katarzyna Rola I live in Austria and I take 2× 50 mg in month. ...every 2 weeks.
Katarzyna Rola：我來自奧地利，而我每兩周使用50mg劑量。
Katarzyna Rola
I am from Poland and we don't now when besremi will be available
我來自波蘭，但我不知道何時能使用Besremi進行治療
Gabriele Ahern
Good Luck Ida.
Let us know how you feel on it and how it works for you....please.😊❤❤❤❤
Ida, 祝你好運。請讓我們知道你對它治療感受以及它對你的影響。
Ida Idic
Katarzyna Rola I think that's this month will be in EU
Katarzyna Rola，我想是這個月會在歐盟銷售
Ida Idic Gabriele Ahern Thank you ....I wìll inform you
Gabriele Ahern，謝謝，我會跟你們說。
Katarzyna Rola
Good Luck Ida Idic!
Ida, 祝你好運。
Marcy Worthington
Congratulations! You're the first person I've heard of who is using Besremi outside of a medical trial.
I've used Pegasys for over ten years and have had excellent results. I hope Besremi is as good for you as Pegasys has been for me!
恭喜！你是我聽到第一個在臨床試驗之外使用(6446) 藥華藥新一代干擾素Besremi的人。
我用羅氏干擾素 Pegasys治療超過十年，並取得了很好的成績。我希望你使用Besremi治療後成效也能像Pegasys對我一樣！
Ida Idic
Marcy Worthington
Thank you ...I am a patient from doctor Gisslinger, that's why it went fast.
Marcy Worthington謝謝，我是Gisslinger醫生的病患，這也是我為何這麼快取得的原因。
Marcy Worthington
You are very fortunate to be treated by an excellent MPN expert!
你很幸運能得到最頂尖的MPN權威醫生的治療！
Kim Christian Hvidkjær
Interesting Ida Idic - as i read it, Besremi is RoPegulated Interferon. Is this PV-specific, or also applicable to other MPN variations?
Ida Idic，這很有趣。我看了一下資料，Besremi 是長效型干擾素，專屬於PV適應症，有適用於其他的MPN 適應症嗎？
Ida Idic
Kim Christian Hvidkjær My diagnosis is PMF CALR +
Kim Christian Hvidkjær，我是 CALR 變異陽性的 PMF 病患。
Greg Giarratana
Is it available in Australia
請問這在澳洲有嗎？
Ida Idic
Greg Giarratana I do not know
Greg Giarratana，我不知道。
David Cray
Ropeg is not on our pharmaceutical benefit system yet but Pegasus is in pre loaded syringes which costs me A$ 39.00 for a four pack.
(6446) 藥華藥新一代干擾素 Besremi 尚未納入藥品福利管理系統，但羅氏干擾素 Pegasus 則是預裝注射器，四包裝售價為39.00 澳元。
Marcy Worthington
I think Besremi, Ropeginterferon, is only available in parts of Europe at this time. David, is Peg Intron available in Australia?
我想(6446) 藥華藥新一代干擾素 Besremi，Ropeginterferon 目前只在歐洲部分地區有銷售。 David，請問澳洲是否有 Peg Intron 上市？
Rosanne Romeo
That means years for it to be available for us in the US.
這意味著這即將在美國上市提供我們使用。
Ida Idic
Rosanne Romeo Ich hope that comes fast to you.
希望這儘快提供你們使用
Rosanne Romeo
Ida Idic Thank you. I hope this new drug works well for you.
Ida Idic 謝謝，我希望這藥物對你成效良好。
Karrie Schwartz
I’ve been on Pegasys for a decade. Funny the things that make one jealous when you get old! Congratulations.
我已經使用羅氏干擾素 Pegasys 治療十年的時間。這件事真讓人嫉妒！恭喜。
Eva Glud
Ida Idic Have you been on Pegasys before? I am also CALR+ MF and did not have any results on PegIntron ie RopInterfron alfa-2b but excellent results with Pegasys ie the 2a version. So how much I would like to space the injections to every second week- I am concerned to change. Have you discussed this with Prof Gisslinger?
Ida Idic，請問你先前是否用過羅氏干擾素Pegasys，我也是 CALR 變異陽性的 PMF 病患，先前沒有任何RopInterfron alfa-2b的成果，但在羅氏干擾素Pegasys 上成效良好。
我想要改成每兩周一針，你是否和Gisslinger 教授討論過此事？
Ida Idic
Eva Glud No, i did not try pegasys before. Only this
不，我沒使用過羅氏干擾素Pegasys，只用過這個。
Rina Straßl
Wow, it's actually a pen! Must be more convenient. 😮 Ich hoffe, du verträgst es gut! Viel Glück!
哇，這是筆狀的，那這必然更方便。Ich，祝你好運，希望用它治療對你成效良好！
Lynn Colwell
David, would you know or would you know how to find out how this is progressing? "PharmaEssentia is continuing to discuss with the US Food and Drug Administration (FDA) the best path forward to make ropeginterferon alfa-2b available to PV patients in the US." I understand it was approved in the EU. This quote is from 2018. https://mpnadvocacy.com/tag/clinical-trials/ Thank you.
David，請問你知道藥華藥美國上市的進度嗎？我從2018年的網頁看到藥華藥正在與美國FDA討論如何向美國PV病患提供使用P1101的最佳途徑。據我了解，它已在歐盟獲得批准上市，謝謝。
Kevin Walsh I tried to research this a few days ago to see if I could find anything new. Unfortunately, no luck for me. Good question.
我幾天前試著看看能不能找到新資訊。不幸的是，我運氣不好。
David Wallace Lynn, I'll poke around and see what I can find out. I think a lot of us are excited about Ropeg.
Lynn, 我去了解看看能找到什麼資訊。我想我們很多人都對藥華藥新一代干擾素P1101感到興奮。
Lynn Colwell Thank you. If it's up for approval in the U.S. you'd think it wouldn't be that hard. Maybe I'll call the company and see what I can find out.
謝謝。如果要在美國拿到藥證，你想這不會那麼難。也許我會打給公司了解看看。
Lynn Colwell Just sent PharmEssentia an email. Can't hurt and maybe they'll respond, who knows. It's interesting that it's a company based in Taiwan.
剛寄e-mail 給藥華藥公司, 也許他們會回, 誰知道。有趣的是這一間公司位於台灣。
David Wallace
I have a contact at PharmaEssentia and asked her about Ropeg approval in the U.S. Here is what she had to say: "It’s currently planned to have pre-BLA meetings with FDA.
Detailed timeline approval date is unknown at this stage and will be upon FDA’s requirement to be fulfilled in the submission."
Here's the definition for pre-BLA meeting - new drug application (pre-NDA) or pre-biologics license application (pre-BLA). These meetings. may be requested by the sponsor to address outstanding questions and scientific issues that arise. during the course of a clinical investigation, aid in the resolution of problems, and facilitate. evaluation of drugs.
我在藥華藥有一個聯繫窗口並詢問在美國的批准狀況。以下是她所說的：“目前計劃與FDA進行PRE-BLA會議。具體的藥證批准時間仍未知，這將根據FDA的需求決定。“
以下是PRE-BLA會議的定義：新藥申請（pre-NDA）或PRE-BLA會議。申請公司可能會要求解決出現而未決的問題以及科學性問題。在臨床調查過程中，協助解決問題，以便有效評估藥物。
Kevin Walsh David - thanks for the follow up on this!
David, 感謝追蹤。
David Wallace You bet Kevin. It boils down to very hush-hush.
Kevin, 你說對了, 這件事很低調。
Kevin Walsh Yeah, that is the way it appears. Do you know if Ropeg has been shown to be any more effective than Pegasys? If not, then is the only advantage that you only need to inject every other week? I don’t know, I’m not sure I see the big advantage over Pegasys unless I’m missing something.
你知道藥華藥新一代干擾素P1101是否比羅氏干擾素Pegasys更有效嗎？如果沒有，那麼P1101唯一的優勢就是每兩周只需注射一次嗎？我不確定我是否有看到比羅氏干擾素Pegasys具備優勢之處，也許是我沒注意到。
Lynn Colwell David thank you. Kevin please check but I believe what I read is inject every two weeks for first year then once a month and from a study, “Ropeginterferon alfa-2b induces significant partial and complete molecular response rates, as reflected by reduction of JAK2 allelic burden.”
David謝謝。Kevin可以再去確認一下，我看到的是第一年每兩週注射一次；而後每月注射一針。此外從一項研究中，藥華藥新一代干擾素“Ropeginterferon alfa-2b可誘導產生顯著的部分和完整的分子反應，正如JAK2等位基因負擔減少所反應的數字那樣。”
David Wallace There were a few mentioned in my interview with Dr. Kiladjian at ASH 2017. Unfortunately the clinical trial was comparing Ropeg vs. HU. Here are 2 key points - patients started on Ropeg with a low dose with slow dose increases, this is a Huge improvement over Pegasys, which can take much longer to find the proper dosage. Improved tolerance of Ropeg is a biggie and I can tell you why from personal experience. I took Pegasys for 18 months and was at 135mcg / week. The side effects were killing me, peripheral neuropathy (and depression) so bad I was going to quit. Once we moved to the combo Peg/Rux, I was down to 22mcg/wk with NO side effects. Another thing is because it will be FDA approved, there will be no insurance hassles.
我在2017年美國血液年會針對 Kiladjian 教授的訪談中提到了一些。不幸的是該臨床試驗比較藥華藥新一代干擾素P1101和HU。這裡有兩個關鍵因素，病患開始使用P1101後，劑量可以緩慢提升，這相比於羅氏干擾素Pegasys有了顯著的改善，這可以有足夠的時間找到合適的劑量。Ropeg的耐受度提升是一個很大的問題，我可以從個人經驗告訴你為什麼。我服用羅氏干擾素Pegasys 18個月，每週135mcg，它的副作用接近殺了我，周圍神經病變（和抑鬱症），糟糕到我要停止治療。而當我改變成干擾素和JAKAFi的合併療法後，我的體重每周下降 22mcg，且沒有任何副作用。
另外一個優勢則是藥華藥新一代干擾素P1101即將獲得FDA批准，這就不會有任何保險申請的麻煩。
Ola Gaston
8月1日下午12:49
Does anyone ever have hand pain?
有任何人會有手痛的狀況嗎?
Amanda Olivarez Cruz Yes 有
Barbara Ellis 有
Kai Osmon 有
Kai Osmon I believe it’s one of the most common things to happen, describe your pain
我相信這是常見症狀之一
Barbara Ellis
Barbara Ellis And the legs,Feet.arms 包含大腿、腳、手臂都有
Kai Osmon
Kai Osmon Barbara Ellis what kind of pain, burning/warmth/tingling ?
是怎麼樣的疼痛，灼熱還是刺痛?
Barbara Ellis All 都有
Barbara Ellis Raynaud's, Fibromyalgia,Hypokalemia 雷諾氏症候群、纖維肌痛以及低鉀血症
Barbara Ellis Chronic Fatigue Syndrome 慢性疲勞症候群
Barbara Ellis The pain is real 很疼痛
Kai Osmon
Kai Osmon Unfortunately this is normal with PV. Are you on any medication? Hydrea, interferon?
很不幸的是這些在PV適應症中是很正常的, 你們用的是HU還是干擾素？
Barbara Ellis I did interferon had problems after a few months had to be taken off I do blood lettings as my body allow it messes with my iron.
我使用干擾素治療幾個月後出現了問題, 他和我身體的鐵混在一起導致我得放血
Kai Osmon Barbara Ellis hopefully ROPEGINTERFERON is going to be the solution for everyone, nobody knows for sure, currently there is phase III of trial. Results of phase 1 and 2 are pretty good, you can google about it
希望藥華藥新一代干擾素 ROPEGINTERFERON 能成為每個病患的解決方案，目前尚未確定。目前有臨床三期試驗。臨床一期和臨床二期的結果成效良好，你可以Google一下。
Barbara Ellis Thanks for the information always looking for answers.
感謝分享, 持續在追尋解答
Kai Osmon
Kai Osmon Barbara Ellis so we do 😉 what else can it be 😁
Barbara Ellis，我們都是。
http://www.pharmaessentia.com/tw/news_latestdetail/%E8%97%A5%E8%8F%AF%E8%97%A5%E5%A6%82%E6%9C%9F%E5%90%91FDA%E6%8F%90%E4%BA%A4Pre-BLA%E6%9C%83%E8%AD%B0%E8%B3%87%E6%96%99
2019.08.08
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本公司如期於美國時間8月5日早上將briefing package送交FDA，並於早上10點接獲通知送件成功。本案係屬於Type B meeting。依FDA規定，Type B meeting一般是在面對面開會60天以前需提出開會目的以及質詢問題，申請舉行會議；俟會議日期訂定後，於會議日期30天前需遞交briefing package。
本公司於今年4月11日與FDA進行面對面討論會議後，已積極依FDA所提示的BLA送件要點，在詹董事長青柳博士親自帶領之下，禮聘統計學權威及血液腫瘤疾病專家，特別包括前FDA副處長級的醫學、統計學、CMC等官員，組成堅強的顧問團隊，幾近20位成員針對前述FDA的送件要點深入探討，定期會議，反覆討論出一致性的意見後，草擬出BLA初稿，編撰出面對面會議的briefing booklet (為briefing package的主要部分)，以供FDA審核員在會議前進行詳細審閱。該briefing package包含待質詢FDA的問題，以及需再與FDA澄清或確認的事項。要言之，本公司在4月11日與FDA進行討論後，於6月底定案提出Pre-BLA會議申請，7月經FDA確認，將於8月28日與本公司召開 CMC會議、9月4 日召開 Non-CMC (Medical) 會議。
依FDA慣例，於面對面會議前，會針對briefing booklet提出問題。本公司向來於開會前一日，會於DC做完整的沙盤演練，以利面對面會議的完整溝通。本公司送件團隊成員與顧問團會依照8月28日與9月4日會議結果，通力合作，盡速進行完整的送件文件撰寫，以求於最短時間內完成準備，目標鎖定年底前送件美國藥證申請。本公司相信，本兩次會議，對於即將到來的BLA送件，將是極為有力的一大助益。
時報資訊
2019年8月8日
【時報-台北電】
藥華醫藥 (6446) 合作夥伴美國Athenex公司(前身為Kinex Pharmaceuticals)於美國東岸時間2019年8月7日上午公佈轉移性乳癌三期臨床試驗結果-口服Paclitaxel和Encequidar(Oraxol，統稱口服紫杉醇)的反應率顯著高於靜脈注射Paclitaxel。
Athenex將以此臨床試驗結果在美國申請藥證、藥華藥亦將以此臨床試驗結果加上24個台灣患者的實驗數據(臨床+PK)申請台灣藥證。未來將與Athenex持續合作，提供一期臨床試驗的數據，以作為第二及第三期臨床試驗設計的依據。
有關口服歐洲紫杉醇藥華將依據合約支付Athenex公司里程碑授權金，截至目前已支付首次簽約200萬美元，後續若各里程碑均達成之授權金最高達700萬美元，包括進行首次臨床100萬美元、進行三期臨床150萬美元、NDA申請150萬美元、台灣藥證核准200萬美元及新加坡藥證核准100萬美元等。有關口服紫杉醇(Oraxol)藥華將依據合約支付Athenex公司里程碑授權金NDA申請30萬美金。
(編輯整理：龍彩霖)
恩慈療法運用 (6446) 藥華藥新一代干擾素ROPEGINTERFERON治療台灣骨髓增生性腫瘤病患
https://journals.lww.com/hemasphere/Fulltext/2019/06001/COMPASSIONATE_USE_OF_ROPEGINTERFERON_TO_TREAT.2094.aspx
HemaSphere: June 2019 - Volume 3 - Issue - p 999
2019年6月期刊
Publication Only: Myeloproliferative neoplasms – Clinical
發表用：骨髓增生性腫瘤-臨床
# Background:
研究背景
There is a high unmet medical need for therapeutic options for patients suffering from myeloproliferative neoplasms (MPN), who have failed or are not eligible to available treatment options. Ropeginterferon-alfa-2b (P1101) is a novel, third generation pegylated interferon-alfa, recently approved by EMA to treat polycythemia vera (PV). Ropeginterferon-alfa-2b is also in the late stages of development in several countries for treatment of PV and other MPNs.
對於治療失敗以及沒有適當的治療選項的骨髓增生性腫瘤（MPNs）的病患而言，這仍存在高度未滿足的醫療需求。(6446) 藥華藥新一代干擾素ROPEGINTERFERON（P1101）是新型、第三代的長效型干擾素，最近被歐盟EMA批准用於治療真性紅血球增多症（PV）。 Ropeginterferon-alfa-2b在某些國家也已進行到研發的最後階段，主要用於治療真性紅血球增多症（PV）以及其他骨髓增生性腫瘤(MPNs)。
# Aims:
研究目的：
Ropeginterferon-alfa-2b is a new and attractive treatment option for patients suffering from MPN who have exhausted all therapeutic options and require treatment. The Compassionate Use Program (CUP) was approved and initiated in Taiwan with the purpose of granting access to P1101 to patients with MPN disease with no therapeutic options who are not eligible to enroll in existing clinical trials for their disease.
(6446) 藥華藥新一代干擾素Ropeginterferon-alfa-2b對於必須無藥可醫且需要治療的骨髓增生性腫瘤（MPNs）的病患是一種極具吸引力的治療選擇。
恩慈療法(Compassionate Use Program)在台灣已獲得批准並已開始進行。主要將P1101用於治療無藥可醫以及沒有資格參加臨床的骨髓增生性腫瘤（MPNs）病患。
# Methods:
研究方法：
Patients were identified that had the potential to benefited from P1101 therapy and were eligible according to the protocol. Patients were treated at a starting dose of 250 ug with subsequent dose escalation every 2 weeks over a 6-week period to 350 ug, 450 ug and 500 ug. Dose adjustments were permitted based on tolerability and efficacy.
為了讓病患可以從 (6446) 藥華藥新一代干擾素P1101治療中受益，因此根據計畫書，病患初期以250ug的劑量開始進行治療，隨後在6週的治療時間內每2週調整劑量分別至350ug、450 ug和500 ug。劑量會針對耐受度和療效進行調整。
# Results:
研究結果：
The CUP currently contains 15 patients from two academic hospitals: 9 with PV, 2 with post-PV myelofibrosis (MF), two with pre-fibrotic MF, one with primary MF, and one essential thrombocythemia patient. The driver mutation was JAK2 in 13 patients, CALR in one, and another one was triple negative. Pre-treatment with hydroxyurea and/or anagrelide was reported in 13 patients. P1101 was given for > 12 weeks to 14 patients (range 4 - 64 weeks). The highest administered dose of P1101 was: 500 ug in 11 patients (time to highest dose - 6 weeks in 9 patients, 10 weeks - in 1 and 20 weeks in another patient); 250 ug, 350 ug and 450 ug in three other patients.
恩慈療法15位病患來自於兩間學術醫院；包含9名PV病患、2名為PV惡化至骨髓纖維化(MF)病患，2名為纖維化前的MF病患，1名為PMF病患，以及1名
原發性血小板增多症病患。
13名病患檢驗出JAK2 突變，其中1名為CALR變異，1名為三陰性。13名病患預先提供HU或 安閣靈(anagrelide) 進行治療。有14名病患使用P1101 進行治療超過12周 (治療時間是4-64周)。11名病患中用P1101治療達最高劑量500 ug (調整到最高劑量時間：9名病患於六周調整到最高劑量、1名病患於10周調整到最高劑量、1名於20周調整到最高劑量)；另外三名劑量則分別為250 ug、350 ug以及450 ug。
The need to decrease or temporarily interrupt P1101 therapy occurred in 4 patients, all due to transaminase(s) elevation. Notably, these events did not require permanent discontinuation of therapy and could be alleviated by appropriate dose modifications. The majority of observed adverse events were of grade 1 and included fatigue, arthralgia, myalgia, chills and dizziness. Grade 2 events included elevation of transaminases (in 3 patients), dizziness, pruritus and lower limbs pain (in 1 patient each). One patient developed elevation of transaminases of grade 3.
Normalization of blood parameters within complete hematologic response range was observed in 3 PV and 2 post-PV MF patients. Two PV patients fulfilled the partial response criteria. In other patients, decrease of platelet count (even in previously treatment-resistant thrombocytosis) and symptomatic improvement were also observed. No major cardiovascular events were recorded. One pre-PMF patient transformed into MF (grade 5). No patients progressed to acute myelogenous leukemia (AML) during the observation.
4名病患減少或暫時中斷P1101治療，主要因肝指數(transaminase(s)升高導致。
然而，這不需要永久停止治療，可以透過調整適當劑量來處理。大多數觀察到的不良反應均為1級，包括疲勞、關節痛、肌肉痠痛，畏寒和頭暈。
2級不良反應包括3名病患肝指數升高、1名病患頭暈、1名病患瘙癢以及1名下肢疼痛。其中有1名病患發生不良反應3級的肝指數升高。
有3名PV病患以及2名PV惡化至骨髓纖維化(MF)病患中觀察到完全血液學反應回到正常數字。2名PV病患符合部分血液學反應標準。在其他病患身上觀察到血小板數量減少（這甚至包含先前治療血小板增多症無效病患）以及症狀改善。沒有發生任何重大心血管事件。一名pre-PMF病患惡化到等級5的骨髓纖維化。觀察期間沒有任何病患惡化到急性骨髓細胞白血病（AML）。
# Summary/Conclusion:
摘要/結論：
In this cohort of MPN patients, not amenable for established treatment options, P1101 demonstrated good tolerability and substantial efficacy. The dose administration schema with a starting dose of 250 ug and escalation to the highest dose of 500 ug within the first 6-8 weeks was feasible, tolerated and allowed rapid control of blood parameters. The observed efficacy demonstrate P1101 as a promising treatment option for patients with MPNs with limited or no alternate therapeutic option. These results mandate access to P1101 at earlier stages of disease as recommended by international MPN treatment guidelines.
在這些沒有合適治療選項的骨髓增生性腫瘤（MPNs）的病患而言，在使用藥華藥新一代干擾素P1101進行治療後，顯示出良好的耐受性和療效。劑量由最初的250ug在病患治療6-8週內調整到最高500ug的劑量證明是可行的、病患耐受度佳而且能夠快速控制病患血液數字。觀察可發現，藥華藥新一代干擾素P1101針對治療方式有限或無藥可醫的骨髓增生性腫瘤（MPNs）的病患而言，是極有吸引力的治療選項。根據國際骨髓增生性腫瘤（MPN）治療指南，這些結果強烈建議早期使用藥華藥新一代干擾素P1101進行治療。
2019.08.08
藥華藥如期於美國時間8月5日早上將briefing package送交FDA，並於早上10點接獲通知送件成功。本案係屬於Type B meeting。依FDA規定，Type B meeting一般是在面對面開會60天以前需提出開會目的以及質詢問題，申請舉行會議；俟會議日期訂定後，於會議日期30天前需遞交briefing package。
本公司於今年4月11日與FDA進行面對面討論會議後，已積極依FDA所提示的BLA送件要點，在詹董事長青柳博士親自帶領之下，禮聘統計學權威及血液腫瘤疾病專家，特別包括前FDA副處長級的醫學、統計學、CMC等官員，組成堅強的顧問團隊，幾近20位成員針對前述FDA的送件要點深入探討，定期會議，反覆討論出一致性的意見後，草擬出BLA初稿，編撰出面對面會議的briefing booklet (為briefing package的主要部分)，以供FDA審核員在會議前進行詳細審閱。該briefing package包含待質詢FDA的問題，以及需再與FDA澄清或確認的事項。要言之，本公司在4月11日與FDA進行討論後，於6月底定案提出Pre-BLA會議申請，7月經FDA確認，將於8月28日與本公司召開 CMC會議、9月4 日召開 Non-CMC (Medical) 會議。
依FDA慣例，於面對面會議前，會針對briefing booklet提出問題。本公司向來於開會前一日，會於DC做完整的沙盤演練，以利面對面會議的完整溝通。本公司送件團隊成員與顧問團會依照8月28日與9月4日會議結果，通力合作，盡速進行完整的送件文件撰寫，以求於最短時間內完成準備，目標鎖定年底前送件美國藥證申請。本公司相信，本兩次會議，對於即將到來的BLA送件，將是極為有力的一大助益。
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