(孤兒藥開發無研發/僅是買賣?) Jeffrey Aronin: …real impact !

美檢討孤兒藥 台廠快應變 2017-03-13 01:26:52 經濟日報 記者黃文奇／整理 孤兒藥市場過去兩個星期在美國掀起了一場大風波，引起美國國會的高度關注，要求相關單位重新檢視「孤兒藥法規的適當性」，若未來法規對孤兒藥發展的利多減緩，將衝擊到部分台廠與國際大廠合作或授權的談判策略。上個月，美國藥廠馬拉松製藥（Marathon Pharmaceuticals）宣布，將旗下用於治療杜顯氏肌肉萎縮症的產品Emflaza，售價訂定為每年8.9萬美元，這個藥才在2月剛獲美國FDA以孤兒藥資格審核通過，並取得上市許可證；有趣的是，此藥物已在其他多國上市，而一年的藥價約為1,000元美元，雙方價差將近80倍。但由於孤兒藥法令保護，藥商在美國擁有七年獨賣期，因此上述案例天壤差距的藥品價格，其實並不須因為市場競爭而有所調整，不過，馬拉松製藥已在各方的討伐聲下，決定暫緩藥物的上市時間。然而，孤兒藥條款的爭議已經引起政府官員的注意，八位民主黨參議員要求藥廠揭露該商品研發與銷售的細節，包含臨床研發成本及在獨賣期間的預期獲利，而三位共和黨參議員則要求美國政府責任局（government accountability office）全面檢視過去孤兒藥的審核情況，以及為維持立法初衷，此一法規是否有修改之需要。國會要求，此次檢視必須將病人的聲音納入調查範圍。上述案件其實是「壓倒駱駝的最後一根稻草」，今年1月Kaiser Health News（美國非營利組織新聞組織） 已針對藥廠是否濫用孤兒藥法令的議題，提出警示。報告中指出，許多大藥廠利用政府所給予孤兒藥的優惠，將市場上非孤兒藥的藥品多次擴大應用在不同罕病上，以獲得政府所提供的福利及增加藥物在市場上的獨占性。據統計，只有約六成五的孤兒藥物，是用於治療單一罕病，另有約有一成五的孤兒藥，是先以「非孤兒的身分」進入市場。仔細檢視，去年全球排行最佳暢銷藥品的前十名，便有七個藥品也同樣享用孤兒藥的鼓勵與優惠原則。最近，因為偽藥而在台灣聲名大噪的降血脂藥冠脂妥（Crestor），為2016年健保給付藥物申報金額的第一名，台灣一年光在此藥物上的花費就超過23億元，但其卻也享有孤兒藥的獎勵，各界質疑，孤兒藥條款立法的原意，是否已遭到扭曲。孤兒藥資格在生技界被視為進入市場的入場券，在法規的優惠條件下，可以有效降低研發成本，因此，以孤兒藥進入市場再擴大適應症的方式，被許多中小型藥廠視為藥物開發的捷徑。近年來，台廠便有多個藥品成功取得美國孤兒藥資格，對於台廠而言，在資源有限的情況下，孤兒藥的開發，確是一個與國際藥廠策略聯盟的籌碼。市場預估，孤兒藥占全球專利藥營收將從2000年的6%上漲至2020的21%，約為2,000億美元的市場，因此孤兒藥市場背後潛在的龐大商業利益，早已吸引了各大廠商的興趣。五年前，賽諾菲收購健讚，就是看上他的罕病藥物開發能力。但需要擔心的是，若美國緊縮孤兒藥市場的利多，勢必將影響國際大廠對孤兒藥的投資興趣，打亂部分台灣藥廠在國際市場的布局。值得慶幸的是，政府對藥廠在孤兒藥開發上給予獎勵，還是被大部分人認為是需要而正面的。美國總統川普上個月在國會演說中，更讚揚了孤兒藥快速審核機制，因此，未來的法規修改，若不針對初次申請藥證的孤兒藥物，則對於台灣的衝擊會相對減少。(本文由鑽石生技投資分析室提供，記者黃文奇／整理)

Marathon Pharmaceuticals is in the spotlight for drug pricing — again  Jeffrey Aronin, CEO of Northbrook-based Marathon Pharmaceuticals, is photographed in 2015. After the price of his company's Duchenne muscular dystrophy drug came under fire, Aronin said Feb. 13, 2017, that Marathon would pause the commercial launch of the drug. (Andrew A. Nelles / Chicago Tribune) Lisa Schencker Contact Reporter  Marathon Pharmaceuticals is only 6 years old, but this week's uproar surrounding its $89,000 muscular dystrophy drug isn't the first time the company — or its CEO — has faced outrage over drug pricing. Monday, only four days after it received regulatory approval to market a drug to treat Duchenne muscular dystrophy, Northbrook-based Marathon said it would pause the commercial launch of the drug whose price shocked patient advocates and members of Congress. The company, which focuses on rare neurological diseases, attracted similar criticism in 2014 after it raised prices on two heart medications. And in 2008, a separate company founded by Marathon CEO Jeffrey Aronin faced a Federal Trade Commission lawsuit related to drug pricing and competition, though that lawsuit was ultimately dismissed. This time around, it is Marathon's drug deflazacort, which will be sold under the brand name Emflaza, that is under the microscope. While approved only last week by the U.S. Food and Drug Administration, the medication to improve muscle function in those with Duchenne has been available outside the U.S. for years. Some U.S. patients have been importing it from abroad for as little as about $1,200 a year. The drug isn't a cure for the muscle wasting disease, which mostly affects boys who typically die in their 20s or 30s, but it aims to improve muscle function in those with the disorder. Efforts to reach Marathon CEO Jeffrey Aronin were not successful Tuesday, and a Marathon spokeswoman did not respond to a request for comment by deadline. Marathon and Aronin have been criticized in the past for the company's drug prices, in one case by the same lawmakers now asking it to reconsider its deflazacort price. After Marathon acquired two heart drugs, Isuprel and Nitropress, from Hospira in 2013, the prices of both drugs increased by nearly 400 percent, according to a letter Sen. Bernie Sanders, I-Vt., and Rep. Elijah Cummings, D-Md., wrote to Marathon in 2014 to request information for an investigation into the prices. Marathon ultimately sold the two drugs to Valeant Pharmaceuticals International. Also, in 2008, the FTC sued Ovation Pharmaceuticals, a Deerfield-based company also founded and led by Aronin. The FTC accused Ovation of violating antitrust laws by acquiring NeoProfen — the only drug in competition with a drug it already owned, Indocin, to treat a congenital heart defect affecting babies born prematurely. Marathon then raised the price of Indocin by nearly 1,300 percent, from $36 to nearly $500 a vial, the FTC alleged. A federal court, however, dismissed the case in 2010, finding the two drugs were in separate product markets, and a federal appeals court affirmed that decision. Ovation ultimately was sold to pharmaceutical company H. Lundbeck in 2009 for $900 million. Aronin served as Lundbeck's CEO and president after the acquisition. Aronin then went on to found Marathon. The Marathon website describes Aronin as a "business leader, life science investor, entrepreneur and philanthropist." He was appointed by Mayor Rahm Emanuel to the board of World Business Chicago and is a founder of Matter, a nonprofit health care technology incubator in Chicago. In a 2015 interview with the Tribune, Aronin said he's focused his companies on drugs for rare diseases because of the difference they can make in patients' lives. "I always worked for those little niches because I felt like I was able to make a big impact on patients' lives, and I felt there was an unmet need," Aronin said. "I was able to really grow those products and see the real impact even though the numbers weren't as big as with the largest brands — they call them blockbuster drugs." Aronin's Marathon has been growing rapidly, especially in recent months. Marathon about doubled its number of employees from 48 in August to more than 100 now, Tim Cunniff, Marathon executive vice president for research and development, told the Tribune last week. In their letter Monday to Aronin, Sanders and Cummings called the $89,000 price for deflazacort "unconscionable." In his Monday letter, Aronin emphasized that the company expected the drug would be covered by insurers, so patients would pay no more than a $20 copay per prescription. He said the company set the price at $89,000 based on the resources it invested to bring the drug to market and complete clinical studies, as well as to fund future research and ensure broad patient access through insurer reimbursement and its own assistance programs. Like Marathon, a number of companies in recent years have faced criticism for increasing prices for drugs they did not create, but rather bought. "Any time you have a drug company raising prices, they're going to talk about their patents and innovation," said Michael Carrier, a law professor at Rutgers University who specializes in intellectual property and antitrust law in pharmaceuticals. "To the extent that this looks like an investment opportunity for a company coming in after all the hard work has already been done then that innovation-based argument seem less persuasive." But Paul Howard, director of health policy at the Manhattan Institute, a conservative think tank, said the Marathon case is unique in that Marathon had to usher the drug through the FDA approval process — it didn't just take an old drug and resell it. "Marathon did something important, and I think that sets it apart from some of the other regulatory arbitrage that … others have done," Howard said.