unhappy

作者：Yael Waknine  
出處：WebMD醫學新聞

　　April 6, 2010 — 美國食品藥物管理局（FDA）以快速追蹤方式核准perifosine（由Keryx生物製劑有限公司製造，以AEterna Zentaris公司取得執照），用於治療反應不佳的末期大腸直腸癌。
　　
　　FDA的快速追蹤計劃被設計來提供新藥加速研發與快速審查，以符合治療嚴重或危急生命狀況未被滿足的醫療需求。
　　
　　罹患再發或末期大腸直腸癌患者經常接受7種核准藥物中2種以上合併或接續治療，這些藥物包括5-fluorouracil（5-FU）、capecitabine（Xeloda，羅氏Hoffmann-La有限公司）、oxaliplatin（Eloxatin，美國賽諾菲安萬特藥廠）、bevacizumab（Avastin，Genetech有限公司）、cetuximab（Erbitux，ImClone系統有限公司）、以及panitumumab（Vectibix，Amgen有限公司）。
　　
　　KRAS基因狀態為野生型且對5-FU、oxaliplatin、irinotecan、以及包括bevacizumab為主之治療失敗的病患，通常會接受表皮生長因子受體單株抗體治療，包括cetuximab或是panitumumab；當這些治療失敗後，並沒有進一步的治療選擇。
　　
　　Perifosine是一種全新的、可能是第一個抑制磷酸肌醇3-磷酸酶途徑Akt活化的口服抗癌藥物，這個藥物也會影響其他與細胞凋亡還有細胞生長/分化有關的訊息傳遞途徑。許多癌症種類都已經觀察到高度的Akt活化，且這也與治療抗藥性及預後較差有關。
　　
　　根據該公司新聞稿，一項隨機分派、控制組控制第三期研究，使用perifosine與capecitabine合併治療罹患反應不佳末期大腸直腸癌患者，預計在2010年的第一季於FDA一個特別計劃評估下執行。
　　
　　AEterna Zentaris主席與首席執行長Juergen Engel博士在公司新聞稿中表示，我們現在期待由合作夥伴Keryx贊助且發起的關鍵第三期臨床研究，這項研究針對北美的治療反應不佳、轉移性大腸直腸癌患者，預計將於2011年完成，該藥品也預計於2012年在美國上市。這些數據對我們讓perifosine在全球上市的努力將會非常有幫助，而在部分國家，我們期待藉由這項研究可以不必再進行額外研究，即可讓這個藥物上市。
　　
　　Perifosine過去由FDA以快速追蹤贊助以及孤兒藥狀態使用於治療再發/治療反應不佳的多發性骨髓瘤，目前在特別計劃評估下的第三期臨床研究中，研究使用於該適應症的效果。


FDA Approves Fast Track Status for Perifosine in Refractory Advanced Colorectal Cancer

By Yael Waknine
Medscape Medical News

April 6, 2010 — The US Food and Drug Administration (FDA) has approved Fast Track designation for perifosine (made by Keryx Biopharmaceuticals, Inc, under license from AEterna Zentaris, Inc) in the treatment of refractory advanced colorectal cancer.

The FDA's Fast Track program is designed to provide facilitated development and expedited review of new drugs that address unmet medical needs in treating serious or life-threatening conditions.

Patients with recurrent or advanced colorectal cancer are often treated with concomitant or sequential administration of 2 or more of 7 approved drugs, including 5-fluorouracil (5-FU), capecitabine (Xeloda, Hoffmann-La Roche, Inc), irinotecan (Camptosar, Pfizer, Inc), oxaliplatin (Eloxatin, sanofi-aventis US, Inc), bevacizumab (Avastin, Genentech, Inc), cetuximab (Erbitux, ImClone Systems, Inc), and panitumumab (Vectibix, Amgen, Inc).

Patients with wild-type KRAS status who fail 5-FU-, oxaliplatin-, irinotecan-, and bevacizumab-containing therapies typically receive epidermal growth factor receptor monoclonal antibody therapy with cetuximab or panitimumab; no further treatment options are available if this treatment fails.

Perifosine is a novel, potentially first-in-class oral anticancer agent that inhibits Akt activation in the phosphoinositide 3-kinase pathway and also affects other key signal transduction pathways associated with apoptosis and cellular growth/differentiation. High levels of Akt activation have been observed with many cancer types and are linked to therapeutic resistance and poor prognosis.

According to a company news release, a randomized, double-blind phase 3 trial of perifosine in combination with capecitabine in patients with refractory metastatic colorectal cancer is expected to begin this quarter of 2010 under a special protocol assessment with the FDA.

"We now look forward to the initiation and sponsorship by our partner, Keryx, of this key registration Phase 3 trial in refractory metastatic colorectal cancer in North America which they expect to complete in 2011, with product launch, in the USA, in 2012," noted Juergen Engel, PhD, president and chief executive officer of AEterna Zentaris, in company news release. "These data will be very supportive of our efforts to register perifosine in the rest of the world, and in some countries, we expect they will be sufficient to do so without any additional studies."

Perifosine previously was granted Fast Track and orphan drug status by the FDA for the treatment of relapsed/refractory multiple myeloma and is currently in phase 3 trials under special protocol assessment for this indication.