6/21/2017
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`This $7,800-a-month cancer drug caused rashes and rarely worked. Now Trump could make FDAapprovals even easier - LA Times
`
`| NDE50242-064.01
`List No: 16502
`
`Tarceva”
`Tarceva”
`(erlotinib) (erlotinio)§=Temadiar
`
`Tablets
`Tablets
`(temozolon
`For Oral Administration
`
`
`
`150 mg
`htablet contains
`en magof erlotinib free base:
`
`,
`
`(THON: See enclosed
`Aonerescrbing information.
`29°C(77-Fy;excursionspermedto
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`
`This $7,800-a-month cancer drug caused rashes and rarely worked. Now
`Trump could make FDA approvals even easier
`By MELODY PETERSEN
`FEB. 3, 2017
`
`(Win McNamee/ Getty Images)
`
`n June, pharmaceutical giant Genentech sent doctorsa letter saying they
`should no longerprescribe a blockbuster drug called Tarceva to most
`patients suffering from lung cancer.
`
`A study had foundthat only a small numberof patients — those with a certain
`gene mutation — might be helped bythe drug, the companysaid.
`
`%
`
`#25
`
`Boothwyn, PA
`Population 5,345
`58.6% of Residents are Female
`Posted on Wednesday, June 21, 2017
`
`Next List
`See The Full List >
`
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`This $7,800-a-month cancer drug caused rashes and rarely worked. Now Trump could make FDAapprovals even easier - LA Times
`ale
`o ax =F 1>
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`
`
`IN WASHINGTON. D.C. FROM
`ary
`|otaadnLae
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`= -
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`UC
`en ee BOOK THIS MINUTE
`eee LiTt
`
`The newsupendeda 2010decision by the Food and Drug Administration to
`greatly expand use of the $94,000-a-year drug, despite warnings from a panel of
`experts that said there waslittle evidenceit actually worked.
`
`The FDA’s decision resulted in more harm than the hundredsof millions of
`
`dollars wasted on a drug that wasineffective for 90% or moreofpatients.
`
`Overthe years, thousandsof patients were prescribed a drug that had no chance
`of helping them but could frequently causeterrible rashes covering their faces
`and bodies, accordingto prescription data and adverse event reports. Some
`patients with the most aggressively growing cancersdied before trying other
`treatments that may have lengthenedtheirlives.
`
`Thestory of Tarceva showsthe danger of approving experimental medicines
`beforereliable scientific data show they are effective — which regulators are now
`doing more frequently.
`
`Pressured by powerful pharmaceutical company lobbyists and often dramatic
`testimony by patient groups looking for hope, Congress has repeatedly loosened
`regulations to speed medicinesto sale.
`
`Somedoctorsfear the bar for approvalwill be lowered even more.
`
`The FDA is now examining how to comply with the 21st Century Cures Act, a law
`Congress passed in Decemberto hasten the approval of drugs and medical
`devices.
`
`Andcritics of the FDA whosaythe review processstill moves too slowly —
`including drug companies,their investors and patients desperate for new
`medicines — hopethat President Trumpwill go even further. At a White House
`meeting with pharmaceutical executives this week, Trump promised them he was
`“going to streamline” FDAregulations.
`
`“Every medicine puts youat risk of side effects,” said Vinay Prasad, a
`hematologist-oncologist at Oregon Health and Science University who has
`studied the FDA’s accelerated approval of cancer drugs. “The question is: Are
`those side effects worth it? For manyof these drugs, we just don’t know.”
`
`An FDAapproval doesn’t necessarily mean
`that a drug works.
`— Brian Shields, ex-Genentech sales rep and whistleblower
`
`htto:/Awww.latimes.com/business/la-fi-fda-tarceva-approval-20170204-htmlstory.htm|
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`
`
`sasaiele
`
`Genentech headquarters in South San Francisco. (Paul Sakuma / Associated Press)
`
`In a written statement, the FDA defendedits fast approval of Tarceva and other
`medicines. The agency said lung cancerpatients had few options whenthe drug
`wasfirst approved in 2004.
`
`The FDAsaidit had limited the drug’s approval to the small numberof patients
`who hadthe mutation soon after Genentech released theresults of the study last
`year showingit did not workfor other patients. The agency had requested that
`studysix yearsearlier.
`
`Howthousandsof cancer patients were
`prescribed a drug that couldn’t help them
`
`The Food and Drug Administration frequently speeds experimental medicines
`to sale by approving them before scientific evidence showsthey work.
`
`For a drug called Tarceva, the FDA's decisions resulted in thousands of lung
`cancer patients taking a drug that could not help them.
`
`Twelve years passed before the agency warned doctors in Octoberthat
`Tarceva only worked for a small numberof patients with a rare gene mutation.
`
`Read more
`
`FDAofficials attributed the delay in limiting Tarceva’s approval to the many years
`it can take to perform a meaningfulscientific study.
`
`“This process of gaining new knowledge about disease and drugefficacy — which
`can significantly modify or even contradict results on which previous drug
`approval decisions were made — is the essenceof scientific advancement,” the
`agencysaid.
`
`Genentech declined to makeexecutives available for interviews. The company
`andits marketing partner OSI Pharmaceuticals instead sent a brief statement.
`
`“Clinical trials answerspecific questions aboutthe safety andefficacy of a
`medicine, but also lead to new hypothesis-generating information,” the statement
`
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`said. “It is not uncommonfor a medicine’s approvedindications to change over
`time.”
`
`Oneof Trump’s possible selections to head the FDA — Jim O’Neill, a Silicon
`Valley venturecapitalist with no education in medicine or science — hasraised
`the idea of approving drugs with notests of their effectiveness.
`
`“Let’s prove efficacy after they've been legalized,” O’Neill said in an August 2014
`speechat a biotech conference.
`
`That would mean morepatients would becomepart of a continuing experiment
`andbe prescribed medicinestheir doctors knowlittle about.
`
`Tarcevais not the only medicinethat doctors are nowprescribing that may not
`workfor mostpatients. In a study, Prasad andhis colleague found that of 36
`cancer drugs approved by the FDA between 2008 and 2012,onlyfive had been
`shown to actually extend survival by 2015.
`
`Someineffective drugs have eventually been taken off the market, but it can take
`years. A drug called Mylotarg was pulled from pharmacyshelves in 2010 — 10
`years after the FDA approvedit for acute myeloid leukemia, a bone marrow
`
`cancer.
`
`A scientist works in a Genentech laboratory in South San Francisco in 2006. (Paul Sakuma/ Associated Press)
`
`Scientists designed Tarceva to block an enzymeassociated with epidermal growth
`factor receptor, or EGFR,a protein believedto playa role in the formation and
`growthof cancer.
`
`In 2004, researchers discovered a gene mutation tied to EGFR,creating a way to
`find those patients morelikely to respondto the drug.
`
`Manypatients with the mutation have lived for monthsor even years while taking
`Tarceva.
`
`Yet for years, Genentech and OSI downplayed the importanceoftesting for the
`mutation orlevels of the protein and avoided using thosetests to narrow the pool
`of patients. Instead the companies’ early trials — and promotion of the drug —
`were aimedat all patients with non-smallcell lung cancer whether they had the
`mutation ornot.
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`Former Genentech scientist Paul Waring explained more aboutthe executives’
`decisions in a presentation at the Walter and Eliza Hall Institute in Australia in
`2014.
`
`Hetold the crowdofscientists that in 2006 Genentech’s commercial team had
`
`estimated the company would lose $150 million a year in Tarcevasalesif in its
`next trial — whichit was planningto look at early-stage lung cancer — it stopped
`acceptingall patients and instead restricted enrollmentto those testing positive
`for the protein.
`
`“Westruggled — boy, did we struggle — with this decision,” Waring told the
`crowd. “The companywasobviously keen to protect its revenue base.”
`
`Yet by keepingall patients in the trials, even though otherresearchers had shown
`10% or less might respondto the drug, the corporate scientists were having a hard
`time showing Tarceva offered an advantageoverthe placebo.
`
`Instead,in thetrials, the few patients who improved dramatically boosted the
`survival results for the overall pool of volunteers taking the drug.Atthetrials’
`end,the group taking the drug lookedjust slightly better than those taking the
`sugarpill.
`
`In essence, eachtrial was a lottery. Only a small numberof patients won even
`
`though the companies sold hundredsoftickets.
`
`Tarceva packagesat Johns Hopkins Hospital in 2005. (Win McNamee/ Getty Images)
`
`WhenGenentech and OSIwent back to the FDA in 2009 andaskedthat Tarceva’s
`approval be expanded,their newtrial showedthe drugincreased survival by a
`month.
`
`The FDAhadinitially approved the drug in 2004 as a treatmentfor severelyill
`patients who hadfailed chemotherapyandhad few other options. Now the
`companies wantedit to be prescribed as “a maintenancetherapy”for patients
`whowerenotas ill and had responded to chemotherapy.
`
`OSIChief Executive Colin Goddardtold investors in July 2009 that the expanded
`approval could add morethan $500 million to Tarceva’s annualsales in the U.S.,
`more than doubling them.
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`To bolstertheir case at a hearing on the proposal, the companiespaid for several
`patients to fly to the FDA’s offices outside Washington, D.C., to testify about how
`Tarceva had savedtheirlives.
`
`Twopatient advocacy groups, which hadreceivedpart of their budgets from
`Genentech and OSI, also pleaded for the expanded approval.
`
`“Mycanceris being controlled by this drug, which I am so thankful for,” said
`Mary LouFisherof Fortuna,Calif., in a statement read at the hearing.
`
`The committee of experts advising the FDA was not swayed. They voted 12-1
`against expanding Tarceva’s approval.
`
`“I think there’s uncertainty, substantial uncertainty, about what the actual added
`benefit is,” said ThomasFleming,a biostatistics professor at the University of
`Washingtonin Seattle, in explaining his vote, according to a transcript.
`
`“Wewerepresented with a single study... that has some design flaws showing
`some very modest or even minimalbenefit,” added Ron Richardson, an
`oncologist at the MayoClinic whoalso voted against the approval. “I don’t think
`the sponsor answered the question on the valueof this drug.”
`
`The FDA did nottake the experts’ advice.
`
`The agency employee signing the 2010 approvalletter was Robert Justice, a
`former Genentech seniorscientist.
`
`The approval further fueled Tarceva’s globalsales to nearly $1.5 billion in 2011,
`according to QuintilesIMS,a consulting firm. American doctors wrote 119,047
`prescriptionsthat year.
`
`In sales brochures, Genentech and OSI touted Tarceva for having “a proven
`survival benefit” and working “in a broad patient population.” Oneflier showed
`an older man reading to a young boy. “For momentsthat matter,” the tagline said.
`
`Brian Shields, a former Genentechsales rep, said he complained in a 2010
`meeting of the Tarceva marketing team that the company was promotingthe drug
`to patients it could not help. His boss dismissedhis concerns,hesaid,telling him
`he “was not a team player.”
`
`Shields later filed a lawsuit as a whistle-blower underthe federal False Claims
`
`Act, which the governmentjoined. The suit claimed Genentech and OSI had
`illegally sold the drug, including by sending doctors and nursesto attendall-
`expense-paid retreats at resorts where they were “groomed”totell others about
`how Tarceva could extend survival in “a broad rangeof patients.”
`
`to wie the widen player
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`This $7,800-a-month cancer drug caused rashes and rarely worked. Now Trump could make FDAapprovals even easier - LA Times
`
`Brian Shields, a former Genentech sales representative, filed a whistle-blower lawsuit, saying the company sold Tarceva to patients that the drug
`could nothelp.
`
`The companiesalso recruited patients whose cancers had respondedto the drug,
`and thentrained andpaid them totalk to others in whatit called the “Patient
`AmbassadorProgram,” his lawsuit said.
`
`The companies discouraged doctors from testing patients for the mutation, the
`lawsuit said, because they knewit would reducesales.
`
`“This is a failure of the system,” Shields said in an interview. “An FDA approval
`doesn’t necessarily mean that a drug works.”
`
`On June 6, 2016, the U.S. Justice Department announced that Genentech and
`Astellas Pharma, a companythat acquired OSI in 2010, had agreed to pay $67
`million to settle the lawsuit.
`
`For bringing thecase to authorities’ attention, Shields received about $10 million
`of that amount.
`
`As you lowerthe regulatory standards you
`open the flood gates to moreof these ineffective
`drugs.
`— Vinay Prasad, Oregon Health and Science University
`
`Three weeks later, the companies sent physicians an “Important Correction of
`Drug Information.” They warned doctorsto stop prescribing the drug except to
`the minority of patients with the mutation. Theletter revealed the results of the
`study the FDA had requestedsix years earlier. It showed that patients without the
`mutation died at the samerate whetherthey got Tarcevaor the placebo.
`
`Genentech andAstellas said they believe their promotional practices were
`“entirely proper and in compliance with the law.” They said they settled the
`lawsuit only to avoid morecostlylitigation.
`
`“It takes years to design clinicaltrials, recruit patients and evaluate results,” the
`companiessaid in a statement. “As we learned more aboutdisease biology, we
`worked with the FDAto design a study that looked at Tarceva in people with
`EGFR mutations.”
`
`Waring, the former Genentechscientist, said in an interview that he believed the
`company had movedasquickly as it could in determining the drug only worked
`for those with the mutation.
`
`“We wereall on a steep learning curve,” he said.
`
`But Prasad, the Oregon Health and Science professor, said the FDA’s lax approval
`standards, combinedwiththesix-figure prices companies can charge for
`unproven or marginal medicines, have encouraged the industry to take marketing
`shortcuts rather than spendresearchdollarsto find true breakthroughs.
`
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`This $7,800-a-month cancer drug caused rashes and rarely worked. Now Trump could make FDAapprovals even easier - LA Times
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`Prasadpointedto a study that found the average gain in survival for the 71 cancer
`drugs approved from 2002 to 2014 wasjust 2.1 months.
`
`“That’s not good enoughfor the people I see in myclinic,” he said. “As you lower
`the regulatory standards you opentheflood gates to moreof these ineffective
`drugs.”
`
`melody.petersen@latimes.com
`
`Follow @melodypetersen on Twitter
`
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`
`Copyright © 2017, Los Angeles Times
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