Innovative if not Transformative ...

• 05.07.2010

From today's edition of the Wall Street Journal and the pen of CMPI board member Mark Thornton:

Three years and more than 80,000 deaths ago I wrote in these pages about a travesty that had occurred at the Food and Drug Administration.

In May of 2007 two unique cancer therapies for the treatment of prostate cancer and osteosarcoma (a type of bone cancer) came under review at the FDA on the same day. Both the new agent for prostate cancer, Provenge, and the new agent for osteosarcoma, Mepact, had shown the ability to prolong lives to a significant degree. And both drugs were summarily rejected. Provenge and Mepact were tossed back to the companies developing them with the directive to do more clinical studies.

This was easy enough for Provenge, due to the return on the risk of investment possible with a new prostate cancer drug and the large number of men with the disease available for another clinical trial. The Dendreon company, makers of Provenge, worked as quickly as possible to redo their already successful trial. The results of the new trial turned out the same as the original, and the drug was finally approved by the FDA last week.

In the three years that it took to duplicate what was already known, upwards of 80,000 men lost their lives to prostate cancer. This is equal to the number of men killed in combat in the Korean, Vietnam and Iraq wars combined.

Those FDA staffers who had a role in preventing the approval of Provenge in 2007 will have to live with this sin of omission. But at least now a powerful new weapon is available to help prostate cancer patients.

Not so for those of us in the American sarcoma community waiting for Mepact. Osteosarcoma effects only 900 Americans, mostly children and young adults, each year. The FDA's stunningly cavalier demand for another clinical trial for Mepact was made with the full knowledge that the repeat effort would require about 900 new patients.

Imagine if a clinical trial for a new asthma or diabetes drug required every single patient in the country to be included not once but twice and you will begin to appreciate the profound predicament those of us in the rare-disease community face when it comes to the FDA's irrational standards.

Recently, hope has emerged that a more humane approach might be taken at the FDA to approve new drugs for exceedingly rare diseases. In an amendment to the 2010 FDA Appropriations law, Sen. Sherrod Brown (D., Ohio) and Sen. Sam Brownback (R., Kan.) inserted language that requires the FDA to explain the unfairness of its policies, which have resulted in about 200 treatments for the over 8,000 diseases categorized as rare.

In March, the new FDA Commissioner, Dr. Margaret Hamburg, appeared before the Senate to discuss the issue. In emotionally moving testimony about her own experiences as a doctor dealing with patients in desperate need of new therapies, she promised "innovative if not transformative" approaches to the problem, saying that "new regulatory pathways could be developed . . . to catalyze activity in areas where there are limited markets." She added that this issue is "of the highest priority in the White House."

In Europe, such creative pathways for regulatory approval exist, and they have resulted in the approval for Mepact in the EU. Mepact is the poster child for all that is wrong at the FDA regarding treatments for rare diseases, and many have hope that Dr. Hamburg is the right leader to address this health crisis.

The approval of Provenge, a revolutionary agent that taps the body's own immune system to fight cancer, ushers in the dawn of the age of cancer immunotherapy. Mepact similarly stimulates the immune system to prolong osteosarcoma patients lives, and it is doing so as we speak for children in Europe with this bone cancer.

Oncologists in the FDA Center for Drugs should show penance for their fatal error and join their European colleagues in approving Mepact without the need for another 10-year long clinical trial. The Americans currently living with osteosarcoma can't wait any longer.

Dr. Thornton worked as a medical officer at the FDA for six years. He is the president of the Sarcoma Foundation of America, which has received modest contributions from a U.S. subsidiary that is owned by the makers of Mepact.

We Are the World

• 05.06.2010

Some patently absurd claims have been made in the wake of health care's passage, but New York Times writer Thomas Friedman and Senate Majority Leader Harry Reid are tied for First Place.

Senate Majority Leader Harry Reid is campaigning in Nevada for re-election and continues to tout the health care law. He recently said, “The most important thing we've done for the country and the world is health care.”

Last month, Friedman posited that passage of the health care law strengthened President Obama’s hand in foreign policy:

“Our enemies surely noticed, too. You don’t have to be Machiavelli to believe that the leaders of Iran and Venezuela shared the barely disguised Republican hope that health care would fail and, therefore, Obama’s whole political agenda would be stalled and, therefore, his presidency enfeebled. He would then be a lame duck for the next three years and America would be a lame power.”

Yes, because I’m sure our health care system is an issue very dear to Iranian president Mahmoud Ahmadinejad.

A majority of Americans stood opposed to the law. More than 20 states have joined in a lawsuit against the federal government challenging the law, with particular emphasis on the individual mandate. And polls continue to show no improvement in public opinion of the health care law.

In this country we don’t pass life-changing domestic legislation so that a president may convey political strength overseas.

With that said, it’s highly doubtful that the legislation had the impact Friedman suggests.

Fidel Castro applauded the health care law as “a miracle.” Castro also said, “It is really incredible that 234 years after the Declaration of Independence ... the government of that country has approved medical attention for the majority of its citizens, something that Cuba was able to do half a century ago.”

Here are some recent pictures smuggled out of Cuba highlighting that medical attention Cubans receive.

After praising passage of health care, Castro then attacked President Obama as a “fanatic believer in capitalist imperialism.”

The goodwill didn’t last long.

Now the World Health Organization Director-General Margaret Chan just returned from North Korea with words of admiration for their health care system. Apparently North Korea does an excellent job of keeping its citizens thin.

“They have something which most other developing countries would envy,” said Chan.

Who would have thought?

Then again, most of the world has been praising Cuba’s health care system for the last 40 years.

At any rate, the point here is that we should not decide health care policy in the US based on the misguided perceptions of our system by other countries. And we should most definitely not use domestic policy as a means of strengthening our influence on foreign policy matters.

Senator Reid and Thomas Friedman ought to know better.

Do Vaccines Cause Autism?

• 05.06.2010

Ed Morrissey at Hot Air has posted an excellent video from Reason TV on the Autism-Vaccine hoopla.

The lesson: Correlation is not causation.

The video is worth checking out:

A Betting Man

• 05.06.2010

Having missed the televised grilling of Goldman Sachs’ executives last week, I just now happened to come across a stunning statement made at the Senate hearings.

Arkansas Senator Mark Pryor went on the attack in front of the cameras accusing Goldman Sachs executives for “betting with other people's money and other people's futures.”

Senator Pryor failed to recognize the blatant hypocrisy in his accusation.

Here is a United States Senator who voted for the health care bill before he voted against it.

In voting against the reconciliation bill in March, Pryor acknowledged the adverse impact of the legislation:

"I believe the package falls short of the criteria of making health care more affordable, reliable, and accessible. As more and more details of the package were released, I spent considerable time weighing the benefits and drawbacks to Arkansas. In the end, I believe this legislation is a step we don’t need to take."

And this man dares lecture financial sector executives?

Where was his concern for “other people’s money” and “other people’s futures” when he voted in favor of the Senate health bill last year?

Mind you, Pryor had a fiduciary duty to his constituents to read and understand this far-reaching and costly legislation. He failed to do that and instead gambled with one-sixth of the US economy.

Some might argue that is far worse than any transgressions by Goldman Sachs.

BIO con brio

• 05.06.2010

At the BIO conference yesterday I had the pleasure of chairing a panel entitled, “Advertising or Freedom of Expression?  Cross-Border Communications and the New World Order.” And a high-powered panel it was.  I was joined by Jack Bierig (Sidley Austin), Marie Kennedy (Baxter) and Ray Kerins (Pfizer). 

An audio recording of the panel can be found on the BIO site (www.bio.org).  

Here are my remarks:

If healthcare is a “right,” then is access to information about healthcare also a right?

Well, where you stand depends on where you sit and, for biopharmaceutical companies, it determines how you act.

And nowhere at BIO 2010 will you find a more lively, engaging, and expert panel to debate this timely and crucial issue than right here and right now.  Welcome to BIO con brio.

What’s going on in the US?  Does the First Amendment still count?  What’s going on in the EU?  Does “information to patients” really mean anything?  In the complex and hyper-bureaucratic world of Brussels, is reform going anywhere beyond just words?

And when it comes to healthcare communications, wither social media on either side of the pond?

Let’s start with a look at what’s going on in Europe.

The situation “over there” can be summed up by James Copping of the European Commission’s Enterprise & Industry Directorate. According to Mr. Copping:

“We have an unsustainable mix of regulations, and the legislation on advertising was largely drafted in the 1980s, before the Internet became a daily feature of many people’s lives.”

In 2006 I debated Mr. Copping. He said, “We must find new ways to regulate healthcare information to patients.” I then suggested that a better way to frame that statement would be to say that “the EU needs to find a better way to facilitate healthcare information to patients.”  To which Mr. Copping replied, “Yes, that’s right.”

Well, that was then and this is now.  But before we see what’s sprouting in pursuant to the shifting of ITP authority from Enterprise & Industry to DG SANCO, let’s turn our attention northwards to Denmark for a disturbing twist and a reminder that “free speech” means something very different in Europe then it does here in the US.

In 2003, Danish journalist Frede Damgaard published information on his website about Hyben Total, a treatment for a wide range of conditions—including gout, kidney and bladder disorders, sciatica, diarrhea, and diabetes. The Danish national regulator in 1999 refused it a marketing authorization. It is still sold as a medicine in Sweden and Norway.

 

Mr. Damgaard’s positive description of Hyben Total’s effects on the symptoms of gout and arthritis led to his being prosecuted in the Danish courts on the grounds that it constituted advertising of a medicinal product whose sale was not authorized in Denmark – and the Danish court specifically cited Article 86 of European Union Directive 2001/83/EC, which defines the concept of medicines advertising.

 

Mr. Damgaard appealed to the European Court of Justice, claiming that his discussion of Hyben Total could not be held to constitute advertising since he had no interest in selling the product, and also that the court decision contravened European Union protections of freedom of expression.  And the ECJ agreed.

 

According to the opinion handed down by the ECJ Advocate General, “a lack of connection between the author of the information and the sellers or manufacturers of the medicinal product and the non-commercial or non-industrial nature of the activity of that independent third party may…be strong indications that a message does not have promotional content.”

 

The advocate general added that this was not an isolated case; similar situations had arisen recently over statements about melatonin in Spain, and in the Czech Republic, over a collection of media features entitled “Yesterday Viagra, today Cialis.”

 

The advocate general concluded that it’s up to individual EU member states “to ensure the correct balance between, on the one hand, the objectives of protecting health and promoting the rational use of medicinal products and, on the other, the right of the party concerned to freedom of expression, taking into account the special protection afforded to the party concerned, if it is established that he is a journalist.”

 

But how do you “establish” who is and who is not a “journalist?”

 

Not a complete victory for the Fourth Estate and uncomfortable silence from the court about free speech for non-journalists. What about free speech for physicians and patients and, yes – even biopharmaceutical companies?

 

And so we return to Brussels.

 

Recent reports have spoken about "renewed optimism" that the EU’s proposed legislation on allowing drug makers to provide information to patients on prescription-only medicines will again start moving through its treacle-like legislative process. The latest thinking, however, is strongly focused on the rights of patients to receive such information, rather than industry's right to disseminate it.

That’s an interesting and important finesse – the rights of a patient to the information but no “right” for industry to provide it.  Hm.

Suggested amendments to the most current consultation document emerged on March 10^th from M.E.P. Christofer Fjellner, who’s reviewing the proposed legislation for the EU parliament's Committee on the Environment, Public Health and Food Safety.

Fjellner’s position is that information on pharmaceuticals should only be made available to patients who are actively searching for it.  In other words, information should be "pulled" by the patient rather than "pushed" by industry.

 

Fjellner believes that companies should not be allowed to provide information on prescription-only medicines on television or in newspapers or magazines. He believes the Internet is the appropriate medium for providing information to patients.

And maybe he's right -- but is there really a difference? 

 

If a pharmaceutical company makes available information on a web page – why is that different than making it available in other media?  And what about patients who do not have access to the Internet -- what about their rights?

 

And what are the ramifications for social media? “The Internet” is, after all, only the substrate.

 

On the upside, Fjellner is calling for patient organizations to be actively involved in implementing the new legislation, working to help create guidelines and a code of conduct. Bravo.

 

But needless to say (and important to share) is the hue and cry this last suggestion elicited from the anti-ITP crowd who immediately objected to the participation of patient groups because of the financial support they receive from “interested parties.  And you know who you are.

 

The environment committee will vote on the patient information proposals this June. After that a plenary vote of all European Members of Parliament will be held in September. It will then go to the Council of the EU for further consideration. Process as proxy for action.

 

The battle lines are drawn. Brussels moves in mysterious ways and “consensus” is a very un-American concept. 

 

EU president Herman Van Rompuy is often referred to as “Haiku Herman” frequently ending his speeches with a composition of this own. And so, in keeping with the transatlantic nature of the topic at hand, let me do the same:

 

Health information.

When will Brussels move forward?

We watch and await.

 

Thank you.

USP's USP

• 05.05.2010

USP also means "Unique Selling Proposition."

Pleased and proud to share the news that CMPI senior fellow Tim Franson, MD has been elected President of the USP Convention.

 

As most of you already know, USP is a scientific nonprofit organization that sets standards for the quality of medicines, dietary supplements and food ingredients. USP’s drug standards are enforceable by the Food and Drug Administration in the United States and USP standards are used in more than 130 countries around the world. USP standards designate the quality, purity, strength and consistency of a medicine, food ingredient or dietary supplement for the benefit of patients, practitioners, manufacturers, and consumers. 

Lynched in absentia

• 05.04.2010

“Cowardice asks: Is it safe?  Expediency asks: Is it politic?  But Conscience asks:  Is it right?”

William Punshon

Strongly recommend that you read “Lynched in absentia” from this week’s edition of BioCentury.Here’s sampler – and it should leave a bitter taste in your mouth.

Based on her performance at last week’s hearing on the safety of Avandia rosiglitazone, Rep. Rosa DeLauro (D-Conn.) would have been quite comfortable in Brezhnev’s Russia, a time and place where political science trumped objective science and public inquisitions were pre-scripted to produce politically correct results.

The focus was allegations that GlaxoSmithKline plc had suppressed evidence about the dangers of its diabetes drug Avandia, and that top FDA officials were too biased by “cozy” relationships with industry or blinded by intellectual myopia to take obvious actions that would have saved thousands of lives. When BioCentury asked DeLauro after the hearing why she hadn’t solicited testimony from GlaxoSmithKline, FDA, or a diabetes expert, she replied that “they probably wouldn’t have wanted to come.” DeLauro, whose subcommittee sets FDA’s budget, noted that the company and agency are engaged in discussions over Avandia, and said she “didn’t want to put them on the spot. When did members of Congress become so solicitous of the feelings of corporate executives they accuse of intentionally killing their customers, or of government officials? Senior management from Goldman Sachs who sweated under the cameras for seven hours at a Senate hearing last week would have appreciated such courtesy.

In fact, GSK spokesperson Bernadette King told BioCentury the company learned of the hearing only a day in advance and “would have welcomed an invitation” to testify. DeLauro also told BioCentury there was no need for other witnesses because she’d invited two “independent experts” — Sidney Wolfe, director of the Health Research Group at Public Citizen, and Harlan Krumholz, professor of medicine and epidemiology and public health at Yale University School of Medicine.

Wolfe may be independent, but he certainly isn’t objective. In over two decades on the job, he’s prided himself on vigorously attacking the pharmaceutical industry and FDA. Krumholtz, a prominent and highly credentialed academic cardiologist, served as an expert witness in litigation against Merck and Co. Inc. over its Vioxx rofecoxib. But he’s not a diabetes expert, nor does he represent the thinking of most cardiologists: he has published comments on Avandia dissenting from a joint American Heart Association and American College of Cardiology Foundation science advisory that concluded the evidence for potential harm from Avandia is “inconclusive.”

DeLauro wasn’t shy about criticizing the agency in its absence, saying that whenever difficult drug safety issues come up it “always appear[s] to act on behalf of the industry.” FDA’s “notion is let us leave this [sic] go on for another several years while people die,” she said. DeLauro and Wolfe repeatedly pointed out that FDA’s John Jenkins had signed the original approval documents for Avandia in 1999 and is now in charge of its oversight, and asserted this somehow demonstrates systemic bias at FDA.

They didn’t note that in 1999 Jenkins was director of the Office of Drug Evaluation II, a position that gave him ultimate sign-off authority on approvals of new molecular entities. Nor did they note that Avandia decisions have been bumped up to Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER).

Wolfe did attack Woodcock, who like Jenkins was not present. The consumer activist said he’s “had many conversations talking with Dr. Woodcock about [drug safety] and she’s just uncomfortable being a regulator,” a charge that would be news to the companies that complain bitterly about FDA’s regulatory actions.

Wolfe, who has called for Woodcock’s dismissal, added that “being uncomfortable being a regulator is incompatible with being the head of the center.”

Wolfe supported this assertion by noting that Saudi Arabia — not usually on the list of the most advanced drug regulators — has banned Avandia. “FDA has more employees [working on] drugs than the rest of the world combined,” but less sophisticated regulatory agencies “are more attuned to public health than the FDA,” he charged.Wolfe conveniently failed to note that the European Medicines Agency has looked at the evidence and decided Avandia can remain on the market.

Star Chamber proceedings featuring half-baked reform ideas and populist attacks on regulators are wrong-headed and ethically challenged. In a better political world, FDA would ignore them.

“Conscience and cowardice are really the same thing.  Conscience is the trade-name of the firm.”

Oscar Wilde

The complete BioCentury commentary can be found here.

Maggie Backtracks on Provenge, Sort Of

• 05.03.2010

Maggie Mahar got beaten up so badly because of her mindless, anti-Provenge stance that she posted this on her blog May 1:

May 01, 2010

The American Cancer Society’s Dr. Len Lichtenfield on Provenge & Prostate Cancer:

Of course, all progress against cancer is in small steps.  But you wouldn't know that from any of her previous posts which consist of one big thumbs down (or another finger) in the face of cancer patients....

True Grid

• 05.03.2010

According to the Pink Sheet, “FDA is designing a five-item grid as a management tool to explain its risk-benefit decisions in a new more concise format. The model that it has created as a working template confirms a truism about its drug approval tendencies that industry has suspected for years: the baseline for FDA approval is a high rating of the severity of the disease being treated and the medical need for the product.”

The agency is developing a grid of the five basic factors that need to be addressed in any decision on the commercial availability of a drug. The top two are the seriousness of  the condition addressed and the need for a new treatment of the condition. Then comes the traditional heart of the NDA package: analyses of clinical data on the benefits of the drug and the risks associated with its use.

Significantly, the fifth fundamental factor is explicitly the level of risk management associated with the product. FDA is going to take it into consideration in every decision; sponsors who ignore or underplay the identification of who should use the product and who might use it will have a gap in their filings.

The grid proposal does not call for a fixed mathematical formula behind each approval. The agency has not tried to reduce the judgments in an approval decision to a rigid calculation.

Judgment?  You mean FDA decisions aren’t black and white?  Egad! Someone had better tell Rosa DeLauro.

In the words of John Jenkins, disagreement "happens a lot in the decisions that we have to make. Very few of the decisions that we make on drugs are easy. Very few of the drugs we see have a dramatic overwhelming benefit with relatively no risk. We see that most drugs have marginal to moderate benefits on a population basis and they have general safety but they have the risks of serious toxicities at some low levels." In other words, every decision is "very complex."

Key take-away is that the FDA is officially moving risk management (REMS anyone?) into the list of key factors affecting new products. And, for better or worse, "judgment" is in the eye of the beholder.

Maggie Mahar Hates New Cancer Drugs

• 04.30.2010

Provenge, the immunotherapeutic vaccine for patients with advanced (terminal) prostate cancer was finally approved.  Maggie (Too Many Cancer Drugs)  Mahar is not happy.  Here's why:  they are made by for-profit companies who can manipulate the FDA in order to market worthless drugs with serious side effects anytime they want.  According to her, making drugs is the easier thing in the world, especially cancer drugs.  Let's go back in time to one of her more lucid postings:

http://www.healthbeatblog.org/2008/02/the-wall-street.html

February 21, 2008

The Wall Street Journal Is Wrong on Avastin

......But focusing only on progression-free survival, i.e. how long a patient can go without a disease getting worse, is no better. As The Moss Report, an online cancer newsletter, notes, progression-free survival means that “a drug may change the shape of the patients' survival curve, but not alter the ultimate outcome. Treated patients may die on average at the same time as those who were not treated; sometimes they may even die sooner.”

In this case, we know that, any additional time comes with significant side-effects. In other words, the FDA’s stance is not just a question of time, but of quality.

Indeed, progression-free survival has the potential to be more devastating than standard deterioration. Imagine if, after two months of cancer stabilization, your loved one died at the same time as another patient who had been in worse shape for longer—that would be quite a blow.

The Moss Report points out that “patients who believe their disease is being controlled can feel an even greater sense of loss and disappointment when the disease again progresses than do those without any illusions about being cured of the disease.” Often abruptly dashed hope is more painful than a longer process, because the latter gives us time to prepare and come to grips with loss. If the Journal really wanted to think holistically about survival and benefits, it would be arguing against FDA approval of Avastin—not for it.

Yet the paper says that the FDA’s reluctance is symptomatic of an obstructionist “bureaucratic culture” bulwarked by “political pressure from Congress, where Members know they can always get headlines by calling for a crackdown on Big Pharma or exploiting public safety anxieties.” This isn’t fair. If we really want to make sure we maximize the benefits of medical science, we need to think hard about the incentives of drug companies—not just those of public officials.

The basic logic of the pharmaceutical industry is as follows: (1) a manufacturer creates a drug and runs trials, showing that it confers some benefit, either large or small. (2) The drug is approved by the FDA for a given use, and eventually for a wider array of conditions so that (3) use of the drug can proliferate across patient populations—thus allowing market share to grow. This leads to (4) increased profit, which leads to (5) nice, shiny Porsches.

These steps—or at least, one through four—make up the fundamental business model of prescription drug companies. All the cost is concentrated in steps one and two—research, development, and haggling with the FDA to get to market. To maximize profit, drug companies want to cut these costs as much as possible.

Now, if the FDA concedes that progression-free survival is enough to warrant approval, it essentially sets the bar very low for these early stages. The message is that manufacturers should go for the low-hanging fruit and focus on maximizing the number of ways to apply existing medications—rather than developing truly innovative new ones. The standard of proof is lower—so why not try and push through existing products, rather than incurring the costs of ground-up development?

No business in its right mind would say “no” to this opportunity. Already, drug companies spend more on promotion than on R & D because the effort is less and the financial reward is at least as promising—if not more so—than that attached to development. "

Of course, because it is so easy to develop cancer drugs.  I am sure Maggie is already planning her foray into the field.  After all, with the bar so low, how could she not...

Speaking of low bars... Why did Provenge developer Dendreon and prostate cancer patients had to wait another 3 years for the FDA to approve the product?

And why do most  developers of cancer drugs lose money?  And as for companies spending more on "promotion" than on R&D, it is a tribute to Mahar's ability to even get the small things wrong:  Drug companies spend 20 percent of their sales on R&D and, according to the CBO, devote 10 percent to promotion.   Last time I checked that's less.  

In any event, here's her 'reasoning' for being against drugs like Provenge and Avastin:

"Are you comfortable with the idea that the extra few months would be available to the wealthy, but not to the rest of us?

Also, if the patient has to pay for the very expensive drug that provides only a minimal benefit, there will be too few customers for the drug, and probably the drug company would stop
manufacturing it.

The only way that drugs like this stay on the market is if taxpayers (who pay more than half of all health care bills) continue to pay extremely high prices for drugs that provide a very small benefit."

On the one hand she writes -- in the very same post -- No business in its right mind would say “no” to this opportunity. Already, drug companies spend more on promotion than on R & D because the effort is less and the financial reward is at least as promising—if not more so—than that attached to development. "

But on the other hand, since the drug really doesn't work -- except for a few --  the company will stop producing it, except if the government also covers the medicine for people who are less well off? 

Should new drugs not be made available because they are expensive and only benefit a few people?  Is she against every orphan drug?

And here are Maggie's warm wishes for those now able to finally access Provenge