國際合作開發肝癌新藥PI-88

             二期臨床試驗成果發表會

肝癌多年高掛國人十大癌症死因之第一、二名，並為世界第五位之常見癌症，目前並無效果顯著的治療方法。早期肝癌以手術切除最為有效，但術後肝癌復發率第一年接近50%，如能減少手術後肝癌再發，就可以嘉惠病人。陳培哲教授建議以肝癌作為澳洲Progen研發抗癌新藥PI-88之適應症，由來自澳洲頂尖大學、英國泰晤士報高等教育全球排名第16的澳洲國家大學克里斯•派瑞士(Chris Parish)教授所發明的，運用在地醫學研究之尖端知識及專業，與基亞公司及包括台大醫院在內之六大醫學中心，成功執行二期臨床試驗。肝癌成為PI-88目前最成功之適應症，不僅建立了國際級臨床試驗的技術平台，向國際展現了台灣臨床醫學的實力以及產官學的整合能力，也彰顯了大學醫院在醫學研究及醫學產業鏈之關鍵角色；此一整合成果，相信將可進一步帶動國內外對於台灣開發新藥的信心及投資。

PI-88抗癌新藥開發，從臨床試驗方案設計、臨床試驗執行、培訓超過20位內外科主治醫師、整合六大醫學中心遵循試驗方案、與美國FDA會議討論、撰寫試驗成果報告等諸多事項。PI-88二期肝癌臨床試驗的執行成功，對於深耕台灣新藥開發產業，具有多面向顯著之正面效益，包括下列數項：

 (1) 踏出新藥開發成功的第一步，提高產業價值：

台灣多年來之製藥產業多以學名藥為主，面臨競爭激烈及利潤偏低等難題，反觀國際藥廠，最大的利潤多來自於專利壟斷之新藥，一旦通過臨床試驗，即可享受高利潤藥品銷售達20年之久，由此可知新藥開發在製藥產業鏈中具有最高的價值。PI-88二期臨床試驗即是新藥開發產業成功的第一步，使得合作國內外公司之市值倍增。

 (2) 開發抗肝癌新藥，造福廣大病患：

肝癌是全世界排名第五常見的癌症，在亞洲國家更常是癌症十大死因的第二、三位。在台灣每年約有19,000新增病例，每年約7,000人死於肝癌，是男性死因第一名，女性死因第二名，目前治療初期肝癌的方式多是以手術切除後追蹤觀察，無藥可用，但術後一年的肝癌復發率仍高達5成，五年復發率高達7成；術後一年的存活率

約8成8，五年存活率僅約4成2；術後死亡的主要原因即為肝癌復發。肝癌復發後只能再度手術、電燒、栓塞、或是等待肝臟移植，通常復發後的一年存活率約8成7，五年存活率僅3成1，開發肝癌療法確是刻不容緩。

由PI-88二期肝癌臨床試驗成果顯示，使用PI-88不僅可以顯著降低手術切除後之復發率，並可大幅延後復發的時間。鑒於初步療效顯著，第三期人體臨床試驗已開始規劃，最快於今年下半年將於台灣、美國、歐洲、亞洲多國同步進行，若三期臨床試驗成功，屆時PI-88將成為全球第一個預防肝癌復發的新藥。

(3) 透過產官學整合，成功建立臨床試驗技術平台：

新藥開發從先期研究、先趨標的﹙Lead Compound﹚研發、臨床前各項實驗到人體臨床試驗，所需投入之時間及資源，並非一般中小型生技公司能夠承擔。基亞公司先選擇聚焦於建立臨床試驗的技術平台，希望透過結合台灣優質的醫學中心及團隊，以最有效率及最符合成本效益之方式，建立完整且符合美國FDA標準的臨床試驗技術平台。第二期肝癌臨床試驗在經濟部支持下，不僅試驗過程完全符合美國FDA臨床試驗的規範，且經與FDA會談，獲得FDA相當正面回應並鼓勵盡快進行三期臨床試驗，可證明本團隊執行臨床試驗的能力以及澳洲和台灣在新藥開發的領域具有能力與利基，而此技術平台未來將可應用於更多不同疾病之開發，創造更大利益。

(4) 提升台灣新藥開發國際能見度，促進國際合作

目前PI-88之相關癌症臨床試驗，以台灣團隊在肝癌的執行進度及成果最佳，透過與FDA直接會面對談及國際研討會發表，大幅提升了台灣新藥開發的國際能見度，也向國際展現了台灣臨床醫學的實力。隨PI-88肝癌二期臨床試驗成果的展現，相信將可為台灣生技產業引進更多的國際合作機會。  

International Collaboration for Developing Anti-Liver Cancer New Drug PI -88

Press Release on Human Data from the Phase II Clinical Trial

Hepatocellular carcinoma (HCC), or in brief liver cancer, has long been the leading cause of cancer death in Taiwan , and is now the 5^th most prevalent cancer in the world. Despite some advances in diagnosis, treatment for liver cancer remains an unmet medical need. Surgical resection provides the only chance for cure although the recurrence rate is up to 50% in the first year after surgery. Reducing recurrence will theoretically benefit the survival of liver cancer victims. Medigen Biotech Corp. (MBC) has devoted herself in developing new therapies for liver cancer. Under the leadership of Professor PJ Chen of National Taiwan University Hospital (NTUH), MBC employed Taiwan ’s state-of-the-art knowledge and expertise in liver cancer to successfully complete an FDA registered Phase II clinical study against liver cancer in Taiwan . Through this trial, not only MBC has built a world-class team on clinical study, NTUH has also demonstrated her turnkey position in bridging basic research and biotech industry. Meanwhile, this collaboration sets the first milestone towards a bright outlook of biotech developments in both Taiwan and Australia .

During the course of PI -88 clinical development, MBC has successfully integrated over 20 experienced physicians and surgeons from 6 Medical Centers in Taiwan to conduct a Phase II Study in accordance with the ICH and FDA guidelines. This achievement illustrates several positive impacts on future new drug developments in Taiwan .

(1)  Striding out the first step towards a prosperous biotech future in Taiwan :  

For years, Taiwan ’s pharmaceutical business has been focused on manufacturing and marketing of generic drugs, a battle-field with limited profits.  Global pharmaceuticals, on the other hand, devoted to developing and marketing of patent-protected new drugs. With marketing exclusivity, the profit generated is enormous. MBC’s successful conduction of PI -88 clinical study is a best proof of value creation a biotech company can contribute in developing a new drug.

 (2) Developing new anti-liver cancer drugs to benefit patients:

Liver cancer is one of the leading causes of cancer death worldwide. In Taiwan , among the 19,000 newly acquired liver cancer patients each year, some 7,000 

succumbed to this malignancy at the end. Despite the introduction of surgery, electrocautery, embolization or transplantation for liver cancer treatment, there has been no approved drug for treating liver cancer so far. High recurrence and short survival remain problematic. The results of the PI -88 Phase II clinical trial indicated that PI -88 has significantly reduced postoperative recurrence rate and delayed the onset of recurrence. Given the positive effects of PI -88, a global Phase III clinical trial will be initiated soon with the hope of becoming the world’s first new drug for preventing recurrence of liver cancer after surgery.

 (3) Integration of various resources for a successful clinical study platform:

New drug development takes long years for a series of pre-clinical, toxicology and human studies which is only affordable for international big pharmas. MBC has focused herself primarily on cancer of Asian importance to start with.  Integrating with the medical expertise from NTUH and the financial supports from the government, a most capable and experienced clinical team for developing world-class new drugs in Taiwan has been verified by the US FDA. The track record thus highlights the niche of Taiwan , and serves as the best proof of the capability Taiwan can deliver to the world.

 4) Demonstration of Taiwan ’s capability towards international collaborations:

The liver cancer clinical study in Taiwan has become the leading indication for PI -88 developments. The bilateral collaboration between Medigen and Progen, an Australian collaborator, on PI -88 has been witnessed by the US FDA, and has demonstrated to the world with Taiwan ’s proprietary capabilities and intention for global collaboration in new drug development, particularly for liver cancer therapeutics.