Summary: Last week, Medicare made the decision to commit to paying $93,000 per patient to cover Provenge, a cancer drug that promises to give the average patient suffering from end-stage prostate cancer  an extra four months–though it doesn’t appear to affect the progress of the disease. 
 For Wall Street investors who had put their money on the Dendreon, the drug’s manufacturer, this represents an enormous win. Cancer researchers also may have reason to cheer:  Provenge could mark a small step forward, opening another door in the long quest to find a cure using a patient’s own immune cells. But it is not at all clear that the government should be paying for the treatment outside of controlled trials. For today’s patients, the danger is that Medicare coverage will give them false hope. After all if the government is willing to pay $93,000, thieir must be a chance that Provenge will save lives, right? Wrong. 

The drug offers absolutely no promise of cure; at best it may extend life for a few months–or lengthen the process of dying, depending on your point of view.  Meanwhile tax-payers and other Medicare recipients are the losers. If Medicare is paying for yet another $100,000 cancer drug that offers only a marginal benefit, it will have that much less to spend on other, more effective, if less exciting treatments.  Finally the decision sets yet another expensive precedent, raising the odds that in the not-so-distant future everyone will have to pay higher Medicare taxes.  At some point, Medicare must just say “No” to drug manufacturers–and begin negotiating for lower prices. 
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Long-time readers may remember Provenge, the cancer drug I wrote about in 2007.  In March of that year an   FDA advisory panel voted 13 to 4 to recommend approval of Provenge. The next day, shares of Dendreon, the drug’s sponsor, doubled. But shareholders did not celebrate for long. Two of the dissenting votes were cast by the panel’s two prostate cancer specialists: Sloan-Kettering’s Howard Scher and the University of Michigan’s Maha Hussain. And they did not just vote “no”—following the hearing, both wrote to the FDA arguing that Dendreon offered no solid evidence that Provenge slow the progression of the disease.

The FDA listened. And it told the company it wouldn’t approve the drug until it had more data. That is when the two oncologists began receiving threatening e-mails, phone calls, and letters. Many were anonymous.

It’s most likely that the hate mail came from investors who had watched Dendreon’s shares climb from $5 in early January to $25.25 in late March—before plunging to $3 and change. One Alabama shareholder expressed his feelings on his MySpace page, where he asked “Hey, Hey, FDA, How Many Dads Did You Kill Today?” while images of Hussain and Scher flash across a backdrop of crooked crosses. Mozart’s “Requiem” plays in the background.

When Scher and Hussain attended the ASCO’s 2007 conference, they brought bodyguards. As I noted at the time, only in a money-driven health care system do physicians who evaluate drugs need paid protection. No doubt patient advocates and some physicians also were disappointed by the FDA’s decision, but very few send death threats to those who disagree with them. My experience at Barron’s taught me that investors are not so restrained.  (See the short post below: “Provenge: A Health Care Story or a Story about a Stock?”) 

In May of 2007 the FDA finally approved the drug– though some cancer experts –such as the American Cancer Society’s Dr. Len Lichtenfield– continued to  expressed misgivings.  I published Lichtenfield’s comments on Health Beat:  “it is important that we keep this development in perspective for what it is,” he wrote, “ one small step in an otherwise complex and still difficult situation.  

“It is not a miracle cure, especially for men with very advanced, symptomatic disease. Inevitably, men (and their families) who have very advanced disease and may actually be near death are going to hear about this treatment and believe that something special has come along in their time of need.  Unfortunately, that is not the case, and their hopes should not be raised as a result of this announcement.” 

 Lichtenfield expressed his hope that Provenge would represent a step, however  small, toward better treatments, but he added: “We cannot ignore the issue of costs. . .  once again Provenge  raises the question of how we spend our increasingly scarce fiscal resources, and whether a 4 month improvement in survival without demonstrated, clear impact on the actual disease itself is giving us what we expect from cancer treatments.”   

But if FDA approval of Provenge marked only a tiny step forward for cancer research, it represented a leap of hope for Dendreon investors. And this week, their faith was rewarded when Medicare officials announced that they have decided to shell out $93,000 for the new cancer treatment.  Medicare’s decision was crucial for Dendreon because most prostate cancer patients are 65 or older: this is the company’s market.  This week, analysts surveyed by Bloomberg projected that Medicare coverage will help Provenge generate $2.3 billion in sales in 2014. 

Over the past five days Dendreon shares have shot up by more than 10 percent; the stock is currently trading at a little over $37. Analysts are predicting that ultimately it will go as high as $55.    
Medicare will seek comment on its proposal before issuing a final version by June 30. But Wall Street doesn’t seem worried that comment from the public will derail coverage.  Meanwhile 15 local Medicare and Medicaid plans currently are paying for the drug. Supplies have been limited, but Dendreon aims to open new plants this year. Private sector insurers have indicated that they, too, plan to cover Provenge. (These insurers usually follow Medicare’s lead.) 

Medicare Hesitated Before Committing to the $93,000 Drug 
To be sure, the path to Medicare approval was not without obstacles.  Medicare is legally prohibited from considering price when deciding whether to pay for a new treatment, and in most cases Medicare automatically rubber stamps any drug or device cleared by the FDA. But last year, Medicare bravely announced that it was going to “review” Provenge before making a decision. 

The decision enraged Provenge shareholders (as well as some patients, patient advocates and physicians) who said the government was looking for a reason to avoid reimbursing for the pricey drug. 

"It's impossible to put a dollar figure on a human life, especially when you're talking about a drug that has such mild side effects," said Jim Kiefert, a prostate cancer patient and advocate who was part of the Provenge study. "Of all the treatments I've had — with surgery, radiation and hormone treatment — Provenge had fewer side effects than any of them."  

On the other side of the argument, an AP story published last week noted  that “bioethicists who study health care decisions say Medicare's ruling on Provenge mirrors the bias of the overall U.S. health system, which emphasizes expensive treatments over basic medical care. Health care costs account for nearly one fifth of the U.S. economy, more than any other country.” 

"We tend to put our health care dollars into very high-tech interventions that produce very marginal improvements,"  Steven Miles, a professor at the University of Minnesota's Center for Bioethics told the AP. "The problem is that we have created a health care system that is uniquely inadequate in terms of access to primary health care, which is where you get the most bang for your buck." 
 

Prostate Cancer Specialists Still Uncertain About Benefit 
When the FDA was considering Provenge, FDA advisor Dr. Scher pointed out that there was no proof of an antitumor effect. "Specifically, there were no data provided of a favorable effect on [prostate-specific antigen], regression or stabilization of soft-tissue or bony disease radiographically, or health-related  development of pain," he wrote (The Cancer Letter 33, 2007). 

Prostate cancer specialists who spoke with Oncology News International a few months ago echoed some of Dr. Scher's concerns. "I'm not sure any clinician can tell who, exactly, will benefit from [Provenge]and it may be difficult to tell on an individual basis if anyone has benefited from it—even as time progresses," said Steven Clinton, MD, PhD, professor of medical oncology at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in Columbus.  

"We do know from the clinical trials that there's at least an estimated four months’ survival benefit associated with Provenge” Dr. Clinton acknowledged. "What we don't have in these clinical trials, though, is any other biomarker evidence that we can use to help us understand who is responding. We don't really see declines in PSA or reduction in the size of measurable tumor masses on bone scans or other imaging.” 

On the other hand, Provenge is a  novel vaccine which use a patient’s own immune cells.  In retrospect we may realize  that it marked a turning point in cancer research , what Dr. Philip Kantoff, and his colleagues described in the New England Journal of Medicine as “the beginning of a new era in the treatment of cancer, one in which a patient's own immune system is harnessed to fight the disease," 
Dr. Clinton agrees: "If one looks at the positive of this, what we have for the first time, after decades of research, is an immune-based therapy for a cancer that has traditionally been marching ahead without responding to any of our immune therapies. This is like getting your foot in the door. I think this is going to open up a great deal of interest by clinical investigators and basic scientists in [determining] how we are going to be better able to harness this knowledge and create even more effective immune-based interventions for this disease." 

In other words, while this particular drug may provide only a minimal clinical, benefit, it might teach researchers part of what they need to learn to develop other vaccines that could represent a major breakthrough in cancer research. For that reason, it would seem to make sense to continue studying the drug in large randomized clinical trials in order to better understand how it work.  But if Medicare agrees to cover it outside of trials researchers won’t get  the information that only a controlled experiment can yield.

The High Cost of Cancer Drugs 

As the Associate Press observed this week when announcing Medicare’s decision:  “A growing number of biologically engineered cancer drugs are being priced in the $100,000 range, including therapies from Roche and Eli Lilly & Co. Last week, Bristol-Myers Squibb Co. received approval for a new melanoma drug that will be priced at roughly $120,000 per patient.” 

I would argue that, at some point, the government is going to have to step in and tell drug-makers that they cannot charge desperate patients whatever they think the market will bear. When someone is dying, the market will bear quite a bit, but neither Medicare nor taxpayers should shell out exorbitant prices for such drugs.  Medicare will have to begin negotiating with drug-makers for lower prices.   
The Veterans’ Administration  has been doing this successfully  for years. Of course, if you negotiate, this means refusing to cover over-priced drugs that provide little benefit. In every other developed country in the world, governments tell drug-makers: “This drug isn’t that much better than the drugs we already have for the same disease. And you want to charge $30,000 more for a year’s treatment? It’s just not worth it.” 

The government and the company then negotiate back and forth. Sometimes the drug-maker won’t back down, and the government refuses to include the drug in its “formulary” of drugs that are covered. It is worth noting that the Mayo Clinic and Kaiser also have formularies. They don’t cover every product out there, though exceptions can made if a patient fits a medical profile which shows that he or  cannot tolerate a less expensive, equally effective drug. The VA also lets doctors go “off-formulary” if medical evidence shows that for this patient, the more expensive medication is needed. But when a doctor prescribes a drug that is not on the list, usually a second doctor has to sign off on the exception. 

Ultimately, if Medicare makes it clear that it will not pay six-figures for drugs that may extend the life of the average patient for just a few months, drug-makers will invest their research dollars in drugs that offer greater benefits.  These may be “orphan drugs” that help relatively few patients, but if the manufacturer can demonstrate that they actually save lives Medicare should and will pay for them.  But drug-makers must learn that they cannot hope to reap Jackpot profits by putting a gun to the head of dying patients.             
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Provenge– A Health Care Story or a Story about A Stock? 
Hat tip to the cancer network’s Jonathan Batchelor for this brief history of  Provenge’s “Wild Ride”

‘Provenge’ Park

If author Michael Crichton, MD, were alive today, no doubt he’d have a field day with the drama surrounding Provenge. Here’s but a sample of the conspiracy theories that are worthy of a medicolegal thriller:

• During a 2005 show, Mad Money host Jim Cramer (CNBC) declared the FDA had rejected Provenge—two years before Dendreon even submitted the product for approval. Two years later, Mr. Cramer advised his viewers to sell Dendreon stock, the night before the FDA advisory panel recommended approval.

• In 2007, separate hedge funds allegedly linked to Bernard Madoff, prostate cancer survivor Michael Miliken, and the Gambino organized crime family were blamed for short-selling of Dendreon stock. Mr. Miliken was an investor in Novacea, a biotech firm dubbed a major Dendreon competitor (www.marketrap.com, July 24, 2009).

• Howard Scher, MD, and Maha Hussain, MD, FDA advisors who took a public stance against Provenge, attended ASCO 2007 accompanied by bodyguards after they received threats (New York Times, June 7, 2007).

• Provenge advocacy group CareToLive accused the FDA of destroying documents related to the vaccine as part of a conspiracy to jettison its approval (www.bnet.com, February 5, 2010).

• A short-selling scandal causes Dendreon’s stock to dive 65% in 75 seconds. The matter is under investigation by the Securities and Exchange Commission (www.bnet.com, March 3, 2010).