Roche羅氏 Perjeta+Herceptin成功用於乳癌手術切除使用 (post surgery): Perjeta營收估41.6億 (2022年)

羅氏藥廠乳癌用藥 試驗成功 2017-03-02 18:03經濟日報 記者謝汶均╱即時報導 羅氏藥廠（Roche）乳癌用藥Perjeta成功完成臨床試驗，分析師預測這款新藥引進的新治療方法到2021年能為羅氏藥廠帶入超過90億美元的營收。羅氏藥廠股價2日盤中一度勁揚6.9%。羅氏藥廠2日指出，若早期的乳癌患者在手術後一邊進行化療，一邊使用Perjeta和羅氏藥廠先前推出的另一個藥物Herceptin，其死亡率及腫瘤復發率都會低於單純使用舊型治療方法的患者。羅氏藥廠十分重視這個研究結果，因為該公司銷售第二名的藥品Herceptin正首次面臨學名藥的競爭。分析師，投資人正在等待羅氏公布這次研究的完整數據，以瞭解新型治療方法的效果可以到達何種程度。羅氏可能在6月的美國臨床腫瘤學醫學會年會上發布結果。

Roche's Perjeta chalks up needed win in Herceptin combo trial, but questions remain  by Tracy Staton | Mar 2, 2017 11:27am Perjeta's top-line victory in a new trial suggests it might nab sales growth in a new group of patients, but until full details are available, "some degree of hand-wringing will likely continue, in terms of just how big the clinical benefit is likely to be," Bernstein analyst Tim Anderson said. Roche got its hoped-for win in a crucial breast cancer trial—at least in principle. The question is how big that win might be. The Swiss-based drugmaker said Thursday that its next-gen HER2-positive cancer therapy, Perjeta, staved off cancer progression in patients at an early stage of the disease whose tumors had been surgically removed. The announcement didn't include detailed data—those will be presented at a cancer meeting this year—but the bare fact of success suggests that a new FDA-approved use could be on the way for the Roche med. The adjuvant trial, dubbed Aphinity, tested Perjeta alongside Herceptin, its gold standard treatment for HER2-positive breast cancer, and chemotherapy. The cocktail is already approved to treat metastatic breast cancer and early-stage disease before surgery, and the after-surgery treatment setting would be a sizable new market for Perjeta to tackle. That would be a welcome development for Roche as its top-selling drugs get ever closer to biosimilar competition. Herceptin's turn could come as early as next year, some analysts say, with patent expiration set for 2019. That doesn't give Roche much time to amp up sales of its other drugs to help absorb the blow—and a new Perjeta indication is one prospect investors have been watching very closely. Compared with patients on Herceptin and chemo alone, patients in the Perjeta combo arm saw a "statistically significant reduction in the risk of recurrence of invasive disease or death," Roche said in a release. The company says it will be taking the data to the FDA and European regulators. Bernstein analyst Tim Anderson said Thursday that the will-it-or-won't-it question on Aphinity has been making Roche investors nervous, despite indications from previous trials that the Perjeta combo would work. The fact that it did, in fact, work is likely to be a boost for Perjeta and could be a stabilizer for Herceptin down the road. The Perjeta combo uses have given Herceptin some help already, as the older drug is used for a longer time period in those indications. And importantly, the trial turned up no new safety signals for the combo. But Anderson figures that the new indication, if approved, won't be an overwhelming driver of new sales."We have viewed the magnitude of the benefit as likely to be modest because Herceptin works pretty well," Anderson wrote in a Thursday note, "yet good safety/tolerability would still drive meaningful sales growth." And until the specifics on the Aphinity results are presented—likely at the American Society of Clinical Oncology meeting in June—it's unclear just how much the new data would change clinical practice. A breast cancer specialist told Bernstein analysts last year that the combo will need to deliver at least a 2% to 3% improvement over Herceptin and chemo alone."Without full details of the data … some degree of hand-wringing will likely continue, in terms of just how big the clinical benefit is likely to be," Anderson noted. His firm now estimates that Perjeta sales would peak in 2022 at about 4.2 billion Swiss francs, or $4.16 billion, up from 1.85 billion francs last year (which itself marked 26% growth). For comparison's sake, Herceptin brought in 6.78 billion francs in 2016. Meanwhile, Herceptin biosims are marching forward. Mylan and Biocon have a Herceptin biosim under FDA review right now, Pfizer's knockoff recently succeeded in a key trial, and Amgen and Allergan together have a version progressing toward the market.

Pertuzumab (Perjeta®) 2012, 十月 7 - 11:21 資料來源：新光藥訊（第119期）  記者：黃士蓉、柯榮川 一、前言 乳癌是女性最常見的癌症，每年全球約有140萬的乳癌新病例且超過45萬人死於乳癌。近年來乳癌的死亡率逐年的下降，因有先進的篩撿技術可以早期發現早期治療，還有不斷研發的輔助治療。乳癌的輔助治療有放射線治療及藥物/全身性治療，藥物輔助治療又分為荷爾蒙治療、化學治療及標靶治療。如何選擇適當的藥物治療可以參考NCCN的guideline。當乳癌發生轉移時，大部分是無法治癒的，但可以因治療方法的選擇及標靶藥物的使用而改善病人的存活率。乳癌細胞的表現是選擇治療藥物的重要指標，當癌細胞上有很多HER2受體時，病人的乳癌就會被診斷為HER2-positive。HER2受體的過度表現是會增加乳癌再復發的機率且影響病人的預後。大約有20%的乳癌病人會被診斷為HER2-positive，此時標靶藥物成為治療的首選。Anti-HER2 療法被建議用於轉移性HER2-positive乳癌的第一線治療，因標靶治療可以改善及延長病人的存活率。常見的Anti-HER2 療法有Herceptin(干擾HER2受體的單株抗體)。Herceptin在乳癌的治療上雖有顯著的療效，但對部分病患其療效還是有限的，因為在治療一定時間後，癌細胞是會對Herceptin產生抗藥性的。值得慶幸的是FDA在2012年的6月核准了另一個Anti-HER2 療法的新藥Pertuzumab (Perjeta®)。Pertuzumab被FDA核准用來治療先前未接受Anti-HER2 therapy或化學治療的轉移性HER2-positive乳癌患者，與Herceptin及Docetaxel併用作為第一線藥物治療。二、Pertuzumab：適應症&作用機轉 癌細胞對Herceptin產生抗藥性的其中一個原因是HER2與其他HER家族中的受體結合形成dimers，加強了細胞內的信息傳導並促進癌細胞成長與形成，Pertuzumab就是針對此抗藥機轉研發出的新藥。Pertuzumab是一重組的HER2單株抗體，作為一個全新作用機轉分類的藥，是第一個被研發的HER2二聚化抑制劑(HER2 dimerisation inhibitor)。藉由與HER2受體的結合，Pertuzumab阻斷了HER2與其他HER receptor(包括HER1/EGFR, HER3, HER4) 的Dimerization (二聚化)。阻斷HER receptor之間的二聚化可以抑制癌細胞內兩個重要的信息傳導途徑：mitogen-activated protein (MAP) kinase及phosphoinositide 3-kinase(PI3K)，進而終止癌細胞的成長，造成細胞凋亡。此外Pertuzumab還會引起antibody-dependent cell-mediated cytotoxicity(ADCC)。Pertuzumab及Herceptin與HER2受體結合的位置並不相同(前者在Subdomain II，後者在subdomain IV)，因此Pertuzumab不會影響到Herceptin的作用，兩者間更會形成協同作用，增強抗癌效果 三、Pertuzumab：劑量&藥物動力學 Pertuzumab在治療轉移性乳癌的劑量：起始劑量840mg靜脈輸注60分鐘，之後每三週一次420mg的維持劑量輸注30-60分鐘。根據在給予481位病患Pertuzumab之後所做的群體藥物動力學分析所得的結果：Pertuzumab在給予第一次維持劑量後很快就會達到穩定濃度，Pertuzumab的平均清除率是(CL) 0.24 L/day，平均半衰期是18天。在年齡、性別及種族之間藥物動力學並沒有顯著的差異。Baseline serum albumin level 與lean body weight對藥物動力學參數也沒有很大的影響，所以Pertuzumab不需依albumin level 與body weight的改變做藥物劑量的調整。藥物動力分析的結果顯示Pertuzumab在輕度(CLcr 60 to 90 mL/min, n=200)及中度(CLcr 30 to 60 mL/min, n=71)腎功能不全病人的清除率與腎功能正常的患者相似，因此不需調整劑量。在治療期間，如果病患因某些原因須延遲投藥，如延遲的時間大於6週，要繼續投予Pertuzumab時就需從起始劑量840mg再開始。