Latest Drugwonks' Blog
Mistakes are the portals of discovery.
James Joyce
In a wise reversal, the FDA will now allow two hours of open public testimony during the first day of the (June 28-29) Avastin hearing.Smart.
In further news, ODAC will vote on the fate of Avastin's breast cancer indication at the agency's hearing on the proposed withdrawal of the claim, marking the third time in four years that the panel has been formally polled on whether the VEGF inhibitor should be used in this population. It voted against approval the previous times.
The announcement that ODAC will have a voting role contrasts with CDER’s original expectation that committee members would be asked to provide advice and recommendations but not vote.
Karen Midthun explains that since this is an administrative hearing, procedures will differ from those of a typical advisory committee meeting and may bear more resemblance to a court case.
According to Karen, "It may help to think of this as, in some ways, like a trial." Representative and will lead the meeting. Panel members will have an opportunity to question witnesses appearing on behalf of Genentech and CDER.
"As with a typical advisory committee meeting, we will ultimately ask you to vote as a committee on the issues that are the subject of the hearing," the letter states. "There will not be an immediate decision by FDA at the hearing. Instead, as with an advisory committee meeting, FDA will consider the committee's input and will announce its own ultimate decision at a later date."
The Pink Sheet opines that, “The decision to give ODAC a voting role would seem to bode ill for Genentech in light of the panel's previous negative reviews of bevacizumab for MBC.”
But there’s a third option other than yea or nay. FDA is leaving an opening for Genentech to hold on to Avastin's metastatic breast cancer indication even if Commissioner Margaret Hamburg determines existing evidence has not demonstrated bevacizumab's efficacy or safety for this use.
Commissioner Hamburg can decide to retain bevacizumab's accelerated approval in first-line MBC while the company conducts additional studies to confirm clinical benefit even after determining that the grounds for withdrawing the claim have been met.
The Pink Sheet reports that Roche/Genentech is seeking a broad label in metastatic melanoma for the just-filed oral BRAF inhibitor vemurafenib (formerly PLX4032) and priority review, which could possibly enable a U.S. launch at the end of 2011.
It's geared as a treatment for the roughly half of metastatic melanoma patients who test positive for the BRAF V600 mutation. A companion diagnostic to test for the mutation has been developed by Roche Molecular Systems, and has also been submitted for approval.
As a personalized therapy for the tough-to-treat disease, the drug has been widely described as a game-changer in melanoma.
Drug companies should not let overeager sales representatives make do-it-yourself Web videos and post them online without review by compliance experts.
Duh.
Warner Chilcott received for a notice of violation letter for a sales-rep-created-and-produced YouTube video promoting its new osteoporosis drug Atelvia (risedronate delayed-release), which featured a female sales representative talking about the drug to an enthusiastic staff member in a physician's office.
The letter was generated by a "Bad Ad" program complaint, and FDA noted that the video was never submitted via a FDA Form 2253 as required.
Oops.
According to the May 5 NOV letter to Warner Chilcott, which was posted to the FDA Web site May 9, "The video was posted by the sales representative on the website YouTube.com under the direction of a Warner Chilcott district manager."
Please note that this does not mean that YouTube is out of bounds. It's not the channel that's non-compliant, it's the content.
Sins of omission are seldom fun.
Reporters interested in scheduling an interview with the authors of the report should contact CMPI Vice President Bob Goldberg at robert.goldberg@cmpi.org
From the Forest from the trees department, The Wall Street Journal reports:
A federal trial judge on Tuesday acquitted a former GlaxoSmithKline PLC lawyer in a high-profile corporate misconduct case, dealing a blow to the government's effort to target individuals in probes of the pharmaceutical industry.
U.S. District Court Judge Roger Titus in Maryland took the rare move of acquitting former Glaxo lawyer Lauren Stevens without sending the case to the jury.
Judge Titus called his summary move to acquit Ms. Stevens a first in his seven-and-a-half years on the federal bench. "The defendant in this case should never have been prosecuted and she should be permitted to resume her career," he said.
Prosecutors had alleged Ms. Stevens obstructed a Food and Drug Administration investigation into whether Glaxo had improperly promoted the antidepressant Wellbutrin for weight loss, a use not approved by the FDA.
The government's defeat points to the difficulty of prosecuting individuals over alleged wrongdoing at large corporations, where teams of people may be involved in a matter and it is hard to show that executives intended to break the law.
Despite calls for prosecution of top Wall Street figures in the wake of the 2008 financial crisis, the Justice Department has brought only a handful of cases against individuals, and lost some prominent cases.
Ms. Stevens's sudden acquittal could hurt other government efforts, including the long-running investigation of Glaxo for marketing issues related to several drugs, said defense attorneys. They said the Justice Department and the Department of Health and Human Services may have to review their larger strategy of targeting executives and lawyers at pharmaceutical companies.
The Justice Department cannot appeal Tuesday's acquittal. "We believe these charges were well-founded and that the jury should have been allowed to deliberate and decide this case," a department spokesman said.
Pharmaceutical companies have paid billions of dollars to settle various marketing-related charges with the government, but only a few executives have pleaded guilty to any crimes.
Government officials have said they decided to go after more individuals to create a stronger deterrent and prevent companies from viewing fines as merely "a cost of doing business."
Prosecutors alleged Ms. Stevens falsely denied that the company had promoted Wellbutrin for unapproved or "off-label" uses, despite knowing that the company had sponsored programs with doctors' groups involving Wellbutrin. Companies are barred from off-label marketing but doctors can generally prescribe an FDA-approved drug for any condition.
Defense lawyers for Ms. Stevens said she provided legitimate and zealous representation of Glaxo and relied in good faith on the advice she received from an outside law firm.
The judge agreed, saying it would be a "miscarriage of justice" to let the case get to the jury.
"We did not have a bad five minutes in that courtroom; if it had been a prize fight, they would have stopped it," said Ms. Stevens's lawyer, Reid Weingarten, who has represented Cabinet secretaries and corporate chiefs.
It is rare for the government to charge a lawyer over advice given to a client, because such conversations are generally protected unless the lawyer is helping the client commit a crime.
Judge Titus's ruling is likely to make such prosecutions rarer still. "There is an enormous potential for abuse in allowing prosecution of an attorney for the giving of legal advice," the judge said.
The government has long been investigating Glaxo over various allegations related to sales of antidepressants Paxil and Wellbutrin, as well as its former popular diabetes drug Avandia. Glaxo hasn't been charged with wrongdoing in these cases, but the investigation is continuing, according to people familiar with the matter.
Its outside counsel, King & Spalding LLP, didn't return calls requesting comment.
The government hasn't said whether the prosecution of Ms. Stevens was part of an effort to push Glaxo into a plea deal. It said in court documents in December that the Stevens case was part of an "ongoing underlying health-care fraud investigation" looking at her and "potential criminal activity by others."
The company has declined to comment on the cases, and it hasn't said under what terms Ms. Stevens left the company last year.
It said Tuesday that it was "pleased" with her vindication.
"The acquittal certainly strengthens Glaxo's hand in negotiations with the government about a corporate resolution of their case," said John Fleder, a defense attorney with Hyman, Phelps & McNamara PC who wasn't involved in the case.
FDA officials and the inspector general of the Department of Health and Human Services have said that the government wants to make more use of an administrative option to punish executives by excluding pharmaceutical company leaders from the industry. That option may look more attractive after the failure of the criminal case against Ms. Stevens.
Companies that employ an "excluded" executive can be prevented from selling products to the U.S. government—which almost all pharmaceutical firms do. In essence, the step can force a company to dump its chief in order to do business with Medicare or the Veterans Administration.
In April, the HHS inspector general created a firestorm in the drug industry when the agency said it intends to exclude the longtime chief executive of Forest Laboratories Inc, Howard Solomon. The company has protested the move and said Mr. Solomon had nothing to do with marketing violations for which the company agreed to pay more than $300 million in civil and criminal fines.
Gary Schwitzer's HealthNewsReview Blog (fully funded by the for profit HealthDialog, a point I raise only because Schwitzer makes a federal case about pharma funding of researchers) runs healthnewsreview.org. He has never found a new drug or treatment worth paying for. Which raises the question of whether or not he would accept the state of medicine in 1980.
Given the guest blog by "Harold DeMonaco, director of the Innovation Support Center at the Massachusetts General Hospital and one of Schwitzer's most active expert story reviewers on HealthNewsReview.org, my guess is he would be delighted to have stopped progress in it's track in 1980. DeMarco said: "Can we afford to continue to pay for treatments that provide what many would call a marginal benefit? Can we afford not to? Although the increase in survival was only 4 months (from 21 months to 25 months), some men survived longer."I am shocked at how uninformed the rant against Provenge and other medical breakthroughs was. In 1980 the average cost for treating colon cancer was $20K, about $42K in 2010. In 1980 the average five year survival rate for colorectal cancer was 50 percent for people age 45 and over among patients whose cancer had spread to lymph nodes Today the average cost of colon cancer therapy is $40K with a 5 year survival rate at a similar stage is 70 percent. The age-adjusted death rate was 17.6 per 100,000 men and women per year. These rates are based on patients who died in 2003-2007 in the US.
Advances in interceding years provided, as you described Provenge (which has extended the life expectancy of end stage prostate cancer patients by 2 years) marginal benefit. That’s on top of a decline in mortality rates from previous treatments and increase screening.
David Cutler noted that “age-adjusted cancer mortality increased by 8 percent between 1971 and 1990, twice the increase from 1950 through 1971. However, between 1990 and 2004, age-adjusted cancer mortality fell by 13 percent. This drop translates into an increase in life expectancy at birth of half a year--roughly a quarter of the two-year increase in life expectancy over this time period and a third of the increase in life expectancy at age 45.” Similarly, Murphy and Topel estimate that a 1 percent reduction in cancer mortality would be worth $500 billion. Since the death rate from prostate cancer has decline by 37 percent since 1992, the worth of that reduction is $18 trillion.
So would you not have spent more money on increasingly more expensive drugs because at that point in time the benefits were marginal.
That begs the question: would he forfeit the gains in health derived by increased screening and better drugs over the past 30 years to buy more of the kind of cancer care we had in 1980. Or his just willing to forfeit gains going forward.
I will let Fox News' Jim Pinkerton who also runs the Serious Medicine Strategy blog introduce our new paper on the human cost of comparative effectiveness research:
Editor's Note: This is an important piece on Comparative Effectiveness Research from the Center for Medicine in the Public Interest, a leading voice in the struggle to improve our national health through the expansion of personal freedom and the advancement of Serious Medicine."
seriousmedicinestrategy.blogspot.com/
Our thanks to Jim Pinkerton for taking our research so..seriously!
The Obama Watch
Hard on Drug Execs, Soft on Dictators
I was in Israel for two weeks hearing nothing but how the Obama administration is tougher (in action and language) on Israel than it has been on the Muslim Brotherhood (the White House seder included a Tahrir Square salad) and Syria's dictator Bashir al-Assad.
Now it turns out that Team O is tougher on drug company CEOs than it is on brutal dictators and a movement whose goal is wiping out Israel. The administration is applying a little used government approach to knee-capping executives it doesn't like by threatening that HHS won't allow Forest Laboratories to sell medications to Medicare, Medicaid, and other government health programs (which means every health plan under Obamacare) unless it tosses the company's CEO, Howard Solomon. According to news accounts, the action is being taken because government lawyers claim that just fining the company billions isn't stopping illegal behavior. But neither Mr. Solomon nor Forest has been found guilty of any wrongdoing. Here's the WSJ account:
The Health and Human Services department startled drug makers last year when the agency said it would start invoking a little-used administrative policy under the Social Security Act against pharmaceutical executives. This policy allows officials to bar corporate leaders from health-industry companies doing business with the government, if a drug company is guilty of criminal misconduct. The agency said a chief executive or other leader can be banned even if he or she had no knowledge of a company's criminal actions. Retaining a banned executive can trigger a company's exclusion from government business.
Can you imagine the administration using this tactic against health IT firms, unions, the New Black Panthers, ACORN, or investment banks? For different reasons for each, the answer is "No."
Health IT firms are the favorite sons of HHS, the New Black Panthers, of municipal officials who milk pension funds and funnel money to their pet projects, unions are -- well enough said -- and investment banks would never be touched because that would trigger panic in the bond markets upon which the administration relies to finance the mounting debt.
So picking on the CEO of a company that has already paid out $300 million in fines to avoid a government lawsuit regarding marketing practices makes political sense, even if Pharma supported Obamacare. My guess is that it will lead companies to be much less likely to make products available to government programs. Or maybe the administration will force sales at specific prices in exchange for a "promise" not to rough up CEOs. That is as close to government extortion as one can get. This, from an administration that promised to be more business friendly.
Meanwhile the threat against Forest and its CEO is more draconian than actions the Obama administration is taking against Assad. The dictator who has slaughtered his people, aided Iran, built a uranium-enrichment facility, staged the Hezbollah takeover of Lebanon, and whose country is soon to be part of the UN Human Rights Council has received a stern warning from the president but nothing more.
As for the administration's toothless response to Assad (well captured by the brilliant Barry Rubin) note how an administration official in quoted in the New York Times on these points:
Administration officials say that while they lack many effective economic tools, they believe Mr. Assad is sensitive to portrayals of his regime as brutal and backward. "He sees himself as a Westernized leader," one senior administration official said, "and we think he'll react if he believes he is being lumped in with brutal dictators."
Is this for real? How cannot one be sarcastic and hypercritical when leading U.S. officials think that a ruthless dictator -- in fact, the most cleverly ruthless dictator in the Arabic-speaking world -- really cares if people in the West say mean things about him."
The administration only picks on people and enterprises it can bully for show, without thinking through the consequences. Meanwhile it avoids taking on real evil or illegal activity when it suits the political goal of the moment and fits those naive narratives shaping the administration's actions. Forest and its CEO paid their debt in full. The effort to can Solomon is gangster government that serves a short-term political purpose while the administration's inaction towards Syria emboldens a chief executive of whom Rubin writes:
It would be impossible to find someone more eager to be a brutal dictator and who does not see himself as a Westernized leader. If this were the "Godfather," Bashar would be Michael, not Fredo.
If the Obama Administration doesn't understand this, it understands nothing. Yes, that's the point. It understands nothing.
A new survey released yesterday by the Massachusetts Medical Society reveals that fewer than half of the state's primary care practices are accepting new patients, down from 70% in 2007, before former Governor Mitt Romney's health-care plan came online. The average wait time for a routine checkup with an internist is 48 days. It takes 43 days to secure an appointment with a gastroenterologist for chronic heartburn, up from 36 last year, and 41 days to see an OB/GYN, up from 34 last year.
As the Wall Street Journal opines, “Combined with insurance regulations that suppress innovation and competition, this reality helps explain why Massachusetts premiums are among the highest in the U.S. The current physician shortage was inevitable without new doctors.”
Massachusetts health regulators also estimate that emergency room visits jumped 9% between 2004 and 2008, in part due to the lack of routine access to providers. The Romney-Obama theory was that if everyone is insured by the government, costs would fall by squeezing out uncompensated care. Yet emergency medicine accounts for only 2% of all national health spending.
Another notable finding in the Medical Society survey is the provider flight from government health care. Merely 43% of internists and 56% of family physicians accept Commonwealth Care, the heavily subsidized middle-class insurance program. The same respective figures are 53% and 62% for price-controlled Medicaid. Government health insurance may be great, but not if it can't buy actual health care.
The Medical Society also finds "a continued deterioration of the practice environment for physicians in Massachusetts."
Mitt happens.
From the pfolks at PhRMA, some interesting state and national data on biopharmaceutical economic contribution to the US economy.
Here’s an interactive map presenting state economic impact data. The data reflect analyses conducted by Archstone Consulting.
To see select thumbnail information, click on an individual state. Subsequent landing pages provide more detailed information, with links to two-page Archstone fact sheets, which include state-specific data on employment, economic output and research and development activity, as well as Battelle fact sheets on states’ efforts to attract and develop a local biosciences presence.
The U.S. fact sheet with national economic impact data is available here.
Now that's a stimulus package.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
