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The push to create a regulatory framework for generic versions of biotech drugs fizzled last year in Congress, as legislators seemed to lose interest after failing to attach the measure to a major FDA reform bill. But now it’s back, and has gained some unlikely friends in the Bush administration.

The FY2009 federal budget, compiled by the administration’s Office of Management and Budget, for the first time explicitly proposes giving the FDA authority to regulate biogenerics. To recap for those joining us already in progress, biotech drugs — formally known as “biologics” because they’re composed of organic material produced by living cells — currently face no threat of competition in the U.S. even if their underlying patents have expired. The FDA has until now declined to even accept applications for generic biologics, arguing that it lacks the legal authority to do so. (The framework that regulates ordinary generic drugs was required passage of the 1984 Hatch-Waxman Act.)

I’ve written about the subject on several previous occasions. For a general overview, see here. I critiqued the biotech industry’s double standard on biogenerics here, and took on another shoddy argument advanced by a prominent VC here.

In the FY2009 budget, however, the administration proposes a “new authority” for the FDA to approve “follow-on protein products” — yet another buzzword for biogenerics. It’s only a single line in the budget — those inclined to see for themselves can find it in the HHS section of the budget on page 425; the PDF link is here — yet it could be a major turning point in this particular battle.

Of course, the budget doesn’t provide any details, which will have to be worked out in Congress. And there are still plenty of potential pitfalls ahead, as the biotech industry has pushed hard for an explicit term of “market exclusivity” that would fence out biogeneric competition for as long as 14 years (see the Biotechnology Industry Organization’s stand here) even if underlying patents have expired. How all that falls out is largely up to Congress. Still, for anyone who thinks biotech-drug monopolies ought to end the same way they do for ordinary drugs, the administration’s decision is a heartening first step.

(Hat tip to this Chicago Tribune article, which happened to be the first one I saw on the subject, although the budget came out almost ten days ago.)

UPDATE: OK, this makes more sense now — apparently the biotech industry itself is pushing for a biogenerics bill this year, according to this AP story, which suggests that the Bush administration is simply taking industry’s cue. Again. Apparently political momentum for biogenerics has grown to the point that it can’t simply be stonewalled, and the biotech and pharma industries think they’ll get a better deal if they can establish fundamental rules under a Republican administration than they would if a Democrat moves into the White House next year. My prediction: The industry will push hard for a regime that throws up as many roadblocks as possible — not just the market exclusivity issue, although that’s a big one, but also in terms of requiring as much onerous testing of would-be biogenerics as they can get away with.

(UPDATED: See below.)

Medical-device startups are booming these days, as VCs throw money at everything from artificial spinal-disc fillers to implantable weight-control “neuromodulators” to vacuum devices that suck blood clots out of blocked vessels. (That appears to be in sharp contrast to biotech; see the most recent funding data here.) What relatively few people understand, however, is the degree to which the device industry benefits from looser regulations than those covering biotech — and how that might change if safety problems lead to changes at the FDA.

That’s exactly the sort of issue outlined in this story in today’s WSJ (subscription possibly required), which takes a close look at the faulty defibrillator leads recently recalled by their manufacturer, Medtronic. Those leads, formally known as the Sprint Fidelis 6949 (see photo above and to the left), are linked to five deaths over the past three years because the leads were likely to break and to deliver large, unexpected and sometimes fatal electric shocks to heart patients.

As it turns out, many — possibly even most — medical devices aren’t necessarily subjected to clinical trials, because they’re considered straightforward modifications of existing products. (Truly innovative devices are almost always run through such trials.) Similarly, the FDA doesn’t typically require manufacturers to conduct additional tests once devices are approved. Neither does the agency monitor reports of safety problems in a systematic way, instead relying on doctors and companies to file reports when issues crop up.

All of those factors converged in the Medtronic case to delay a final determination about safety problems with the Sprint Fidelity leads for more than six months. Although doctors at the Minneapolis Heart Institute suspected problems back in January, Medtronic didn’t recall the leads until earlier this month. The FDA played a largely passive role, relying mostly on Medtronics’ analysis of its own safety database even as other doctors raised alarms.

The remedy isn’t clear. The FDA, pushed by Congress, is starting to become somewhat more proactive about tracking and analyzing problems with devices and drugs, but its reforms are still in their infancy. Meanwhile, there’s concern — some of it legitimate — that forcing manufacturers to conduct additional clinical trials could slow the pace of innovation in the field. Should that happen, though, the device makers who have taken advantage of today’s lax rules may have no one but themselves to blame.

UPDATE: The WSJ health blog has a good summary of the WSJ story here.

(UPDATED: See below.)

Personalized medicine — the idea that doctors will one day tailor your medical care based on your genetic profile — has been a long time coming, as I’ve previously written. As it turns out, that’s no fault of the Food and Drug Administration, which has emerged as one of the biggest fans of the concept. Yet the FDA is now pushing ahead with efforts to pair drugs with genetic tests in a way that has alarmed critics, who claim the agency is forging well ahead of the medical evidence, as the WSJ’s Anna Wilde Mathews reports today.

The current controversy involves warfarin, a one-time rat poison now commonly used as an anticoagulant designed to prevent dangerous blood clots from forming. The generic drug was prescribed more than 30 million times last year, but because it can sometimes cause patients to bleed excessively, it also frequently sends people to the emergency room — 43,000 times a year, by one estimate, making warfarin the second-most dangerous drug after insulin.

Roughly a decade ago, evidence began to emerge that genetic differences between patients might explain why some people were more likely to experience bleeding on the drug. In particular, researchers identified two genes that seemed to play a major role in modulating warfarin’s effects. Some variants of the gene CYP2C9, for instance, appeared responsible for breaking down the drug more slowly, meaning that it tended to linger in the blood, effectively mimicking the effects of a higher dose. Variations in another gene, VKORC1, affect how the body processes vitamin K — a crucial finding because warfarin’s activity depends in part on its ability to interfere with vitamin K.

The FDA concluded that patients with some of these genetic variations should probably receive lower initial doses of warfarin — which is exactly the sort of thing personalized medicine is supposed to do. Today, the WSJ reports, the FDA is scheduled to announce changes to the warfarin label that urges lower doses for patients based on their genetics, albeit with a variety of caveats.

Many doctors, however, think the FDA has moved too fast. The genetic tests, which cost between $300 and $500, are covered by Medicare but not many private insurers, and doctors fear that patients who don’t get them and end up with bleeding problems may sue. It also takes time to get results from genetic testing, meaning that doctors aren’t necessarily any better informed when starting patients on warfarin, often following a heart attack, a stroke, or another blood-clot-related problem.

Adding fuel to the fire is the fact that the link between the genetic variations and better patient outcomes hasn’t been fully established by the field’s gold standard of evidence, a prospective randomized, controlled clinical trial. So one of the fascinating aspects of this story is that it pits two of medicine’s emerging trends — personalized medicine and evidence-based medicine (see our coverage here) — directly against each other.

Has the FDA acted precipitously, or is it pushing forward where other parts of the medical establishment fear to tread? Feel free to give us your take in comments.

UPDATE: The FDA statement is now available here (hat tip: Pharmalot).

(UPDATED: See below.)

Catching up on a few life-science related items you may have missed over the weekend:

If you prick a cyborg, does he not bleed? — The WaPo’s Joel Garreau brings us this fascinating story about Peter Houghton, the first permananent recipient of a “left ventricular assist device” — a mechanical replacement for a failing chamber of his heart. Houghton’s heartbeat no longer goes lub-dub — instead, it whirrs as an impeller pushes blood through it. He has an electrical socket in his skull that connects his heart device to a camera bag filled with batteries. Worst of all, he’s become “less sympathetic in some ways,” he tells Garreau. “You’re an invented person trying to cope with it, trying to deal with the emotional context of it…. You become coldhearted. The thought doesn’t agree with me, the fact that it happens. But I don’t know what to do about it.”

The psychological problems of this latter-day cyborg are real, although as the story points out, no one knows if they’re the result of surviving a life-threatening illness, the machinery, the drugs Houghton must take, depression, advancing age or the absence of unknown hormones produced by the heart. Houghton spent some time contemplating suicide, but backed away in part because he couldn’t overcome his fear of actually choosing a method. (Antidepressants also seem to have helped.) He’s writing a book titled Cyborg Life and has even tried his hand at poetry:

A roller coaster.
Better than being dead, I think.
Three days out of five.

Provenge and the private eye — Pharmalot’s Ed Silverstein brings us the interesting tale of a plaintiff’s private investigator who stalked the editor of Cancer Letter, a newsletter that ran leaked letters critical of Dendreon’s cancer vaccine Provenge, which we’ve written about at length here and here. (The FDA asked Dendreon for more Provenge data, despite the previous endorsement of its advisory panel.) The plaintiffs — representatives for patients who want the FDA to reverse its Provenge decision — are now suing FDA officials and one of the two advisory-panel member whose critical letters ended up in Cancer Letter; they’re trying to figure out who leaked them to the newsletter.

Earmarking, a habit that’s hard to kick — The NYT’s Robert Pear reports a nice piece detailing how members of Congress — mostly Democrats, apparently — are steering Medicare money to select hospitals through the practice of “earmarking,” or inserting language that directs funding to a particular lucky recipient. Despite the Democratic leadership’s promise to make earmarking more transparent by listing them openly — something I’ve grappled with in a biotech-related context here — Pear found earmarks worth hundreds of millions of dollars hidden away in a House bill designed to expand health insurance for lower-income children.

Amgen’s Sharer called on to resign — Also from Pharmalot comes news of an Internet petition demanding the resignation of Amgen’s CEO, who has overseen a sharp decline in the biotech giant’s stock price amid accusations that the company has pushed overuse of anemia drugs which have been linked to various severe side effects. It’s likely to be about as effective as most Internet petitions, but it certainly doesn’t improve the climate for the embattled biotech.

American life expectancy outpaced by 20% of the globe — This AP story (courtesy of the Boston Globe) reminds us of a major cost of our dysfunctional healthcare system: We’re not living anywhere near as long as people in other countries. In fact, the U.S. has been sliding for years in global rankings of life expectancy. A baby born in the U.S. in 2004 can expect to live 77.9 years, ranking the U.S. 42nd in the world. Twenty years ago, we were 11th. UPDATE: Apparently we’re slipping in other respects as well. This WaPo story notes that Americans are no longer the world’s tallest people, either — the Dutch and other Europeans are now looking down on us. This observation isn’t entirely frivolous, either, since height is a proxy — albeit somewhat indirect, but still meaningful — for general health.

How to get, and keep, health insurance — Those not fortunate enough to work for a large company who provides health benefits already know that the individual-insurance market can be a scary place, at least if you’re not young and healthy. In most states, insurers have no compunction about denying you coverage for a variety of pre-existing conditions or if you take common prescription drugs, such as statins that lower “bad” cholesterol. What’s more, many insurers also ask if you’ve ever been denied insurance in the past, which if you answer truthfully — and lying is a bad idea — makes you a prime candidate for subsequent rejection again.

So it was quite a relief to find this LA Times advice on getting and keeping health insurance. Some of the advice is California-centric — it appears, for instance, that state law may require employers to extend your insurance for up to 36 months if you leave or are fired — but it’s still a good rundown of your rights and the pitfalls you can face in trying to protect your health and that of your family. For non-Golden State residents, there are plenty of other resources available — try, for instance, healthinsuranceinfo.net, which provides state-specific information compiled by the Georgetown Univeristy Health Policy Institute.

Flip switch for stem cells – Three research teams reported a technique for “reprogramming” skin cells into embryonic stem cells, those primordial bits of protoplasm that can propagate themselves indefinitely and, under the right conditions, transform themselves into any type of cell in the body. Deriving embryonic stem cells normally requires destroying an embryo — the main reason research with the cells remains limited, as does federal support for the work.

Teams from Kyoto University, MIT and a Harvard-UCLA collaboration all confirmed a report last year out of Kyoto that skin cells could be reprogrammed by implanting four genes that produce proteins called transcription factors, which control the effects of other genes. Adding those four factors kicked off an intracellular chain reaction that reverted the skin cells to a primordial, “pluripotent” state characteristic of embryonic cells.

There are, of course, a number of caveats, the most significant of which is that the work so far has only succeeded in mouse cells. Extending it to human cells may be tricky, in part because they will likely require additional transcription factors. What’s more, at least one of the transcription factors used in the mouse experiments appears to contribute to cancer; so may the type of virus used to transfer the transcription-factor genes into skin cells. As a result, it’s not yet clear whether the embryonic stem cells produced this way could be used to help regenerate damaged tissue or organs in humans, such as dopamine-producing neurons for Parkinson’s patients or insulin-secreting pancreatic cells for diabetics. All that said, it’s a very encouraging step forward, both in terms of advancing understanding of stem-cell biology and the potential for altering the ethical landscape for the work.

For more, see the WSJ and the NYT.

The trials of Avandia, continued — The fracas over the controversial diabetes drug continued to throw shrapnel in all directions, leaving almost no one unscathed. Avandia’s maker, GlaxoSmithKline, published interim data from a large trial of the drug in the New England Journal of Medicine and touted it as evidence of the drug’s safety — only to find it accompanied by three editorials nitpicking the data and arguing that the data did little to allay doctors’ concerns. In congressional hearings today, a diabetes expert said he was berated by a company official and threatened with a lawsuit for raising questions about Avandia’s safety several years ago. Then the FDA commissioner told Congress that the agency would require strict new warning labels on Avandia and a similar drug.

The FDA, meanwhile, faced charges that one of its drug-safety officials was reprimanded after earlier recommending exactly those warnings for Avandia. And congressional Republicans went after Cleveland Clinic cardiologist Steven Nissen, who first raised the alarm about Avandia almost three weeks ago, suggesting that he had colluded with Democrats to embarrass the FDA and to enhance his chances of one day becoming FDA commissioner himself. As if all that weren’t enough, the NYT also asked if GSK’s efforts to promote Avandia to African-Americans may be backfiring.

Whew.

In research, where you stand depends on who’s paying the bills – An unusual report in the journal PLoS Medicine found that research studies sponsored by drugmakers were 20 times more likely to favor the companies’ products than trials with no disclosed funding source. Conclusions drawn by the research scientists involved — apart from the data itself, that is — were 35 times more likely to favor a sponsor’s drug, the PLoS Medicine study found.

The study looked at nearly 200 published trials of the cholesterol-lowering drugs known as statins to gauge what effect the source of funding had on the results. The research team noted that several factors could account for the tremendous slant in favor of sponsors’ products, including the fact that drug companies might squelch negative studies instead of publishing them and the possibility that trials might be deliberately designed in order to skew the results. For more, check out this San Francisco Chronicle story.

Cancer drug news – The year’s biggest cancer meeting, the annual gathering of the American Society for Clinical Oncology, took place in Chicago over the weekend. Here are a few highlights you might have missed:

• Meeting focus shifts from new drugs to new applications for old drugs (Business Week)
• New drugs show promise for liver cancer (WSJ)
• Biotech Telik reveals that its ovarian-cancer drug Telcyta not only didn’t work, it apparently killed women five months sooner than those receiving standard treatment; FDA orders halt to current Telcyta studies (Bloomberg, TheStreet.com)

California pension fund, private-equity money chase healthcare “cost-cutting” – Calpers, the largest pension fund in the U.S., invested $700 million in Health Evolution Partners, a private-equity fund run by a former Bush administration health official that aims to find ways to reduce the cost of healthcare. According to the NYT, the fund will focus on new ideas such as remote monitoring of elderly or demented patients in order to keep them out of nursing homes longer, telemedicine, chronic-disease management and genomics-based “personalized medicine” that tailors treatments to individual genetic profiles. One thing the fund will not be looking at, though, is electronic health records, which HEP founder David Brailer championed for two years in the Bush administration without much impact; he terms the field “a saturated market.” (See also this story in the SF Chronicle.)

I laid out some early thoughts on high-tech approaches to the healthcare crisis in this piece on Andy Grove’s reform crusade. In general, many of the things Brailer is interested in strike me much the same way Grove’s ideas did — that is, as worthy but woefully insufficient efforts if you expect them to actually reduce healthcare costs. Truly tackling the problem of costs means addressing structural failures of the system, including the current fee-for-service system that rewards doctors financially for doing more procedures or prescribing more drugs regardless of whether or not they help patients. In addition, it wouldn’t hurt to find out more about which medical treatments help patients most — which the NYT’s David Leonhardt addressed here and which I wrote about here — which probably also ultimately means restricting the use of the treatments deemed less effective.

Viewed against that backdrop, Health Evolution Partners and Calpers may be doing little more than spitting into the wind.

Speaking of healthcare reform – The WSJ weighed in with this piece on why the subject of healthcare reform doesn’t send politicians fleeing anymore. The usual suspects — rising health-insurance premiums and out-of-pocket costs, the growing numbers of uninsured Americans — make their obligatory appearance, but the really interesting nugget is how the insurance industry is angling to co-opt reform rather than opposing it outright as it did with the Clinton plan in 1993-94. That alone speaks volumes as to how thoroughly fed up many Americans have become with the ramshackle mess we call a healthcare system.

And while we’re on the subject – One of the major Bush administration healthcare-reform initiatives — besides the smashing success of electronic medical records, that is — was to push Medicare to institute financial incentives that would reward doctors for providing better care. Such “pay for performance,” however, seems to be falling short, according to a pilot study published in the Journal of the American Medical Association and described by the WSJ. In that study, 54 hospitals in the “pay for performance” plan did no better at improving medical practices than 446 hospitals that weren’t offered the incentives.

Gates to measure global public-health performance – No, not all by himself. The Bill and Melinda Gates Foundation, however, gave the University of Washington a $105 million grant to track the impact of public-health programs on a worldwide basis. From the WSJ article:

The new institute will be headed by Christopher Murray, a professor at the University of Washington, who previously served as director of a public-health program at Harvard University and as an official at the World Health Organization. The institute’s missions will include collecting and analyzing data on health trends, such as the prevalence of major diseases and the availability of health services, as well as conducting independent evaluations of the effectiveness of health programs.

The plan reflects the Gates foundation’s strategy of using statistical measures to determine the effectiveness of its grant-giving. The institute will disseminate the information it gathers about global health issues, programs and giving, officials said.

Institute officials pointed to the dearth of available statistics in global health, contrasting that to business, which runs on clear results. “It would seem strange that we would need an institute like this,” Dr. Murray said. But in public health, “we’re so far behind the norm in other sectors.”

The grant is the foundation’s second aimed at gathering better global public-health information.

The first time you hear it, “evidence-based medicine” sounds like one of those goofily redundant phrases like “animated cartoon” or “past experience.” Aren’t doctors always carrying out studies of one sort or another? Isn’t medicine evidence-based already?

Well, no, not really. One of the biggest and least-understood problems in the U.S. healthcare system is that where many new drugs, medical devices and surgical techniques are concerned, there’s relatively little data as to which benefit patients most and under what circumstances. (See, for instance, today’s NYT column from David Leonhardt.) In part, that’s because there are relatively few incentives in today’s healthcare system for anyone to carry out such studies. For instance, it’s taken well over a decade to learn that unblocking partially clogged arteries fails to prevent heart attacks anywhere near as well as inexpensive drug treatment.

In principle, then, evidence-based medicine, which aims to scientifically measure and ultimately standardize medical practice systematically, sounds like something just about everyone could get behind. In practice, though, it all depends on whose ox — or ideology — is being gored by the evidence.

To see that, you don’t need to look any farther than the controversies that rage whenever the FDA rejects or postpones a drug approval for lack of sufficient evidence. Earlier this week, for instance, the NYT reported that two researchers who served on an FDA advisory panel received threatening e-mails and other messages after they opposed the approval of Provenge, a new type of “cancer vaccine” designed to trigger the body’s defenses against prostate tumors.

The researchers — Howard Scher of Memorial Sloan-Kettering Cancer Center and Maha Hussain of the University of Michigan — were concerned that the data offered by Provenge maker Dendreon didn’t actually prove that the vaccine worked. Although Scher and Hussain were in the minority when their panel voted to recommend approving Provenge, the FDA eventually concurred with the dissenters and said it would withhold approval until Dendreon produces more data.

To judge by the reaction, you’d think the FDA was having men with prostate cancer lined up and shot. My former WSJ colleague Marilyn Chase reported that “stunned” patient advocates vowed to deluge the agency with protest e-mails and to continue pushing for early access to the drug. One typical reaction came from Steve Fleischmann, a prostate-cancer survivor and advocate. “I feel very, very let down,” he told the WSJ. “What does this say to men who have prostate cancer and want to stay alive?”

Those were the measured reactions. A Sloan-Kettering spokeswoman told the NYT that Scher received phone calls and e-mails, including one titled “your murder.” Another letter writer told Scher, “You should get cancer.” Commenters on the WSJ Health Blog, whose three items on the FDA decision drew an outpouring of vitriolic attacks on Scher, Hussain and the FDA, accused the researchers of unethical behavior and FDA officials of shorting Dendreon’s stock or colluding with hedge funds. One commenter called the FDA decision “MASS MURDER” because it denied patients a promising drug.

It’s impossible not to empathize with people who consider Provenge the last hope for their loved ones or themselves. On the other hand, the evidence that Provenge actually works is slim indeed, while Dendreon seemed determined to spin it as hard as possible. (For a recap of the company’s incredible sloppiness with those clinical trials, see my earlier piece on Provenge.) In other words, Dendreon opportunistically took whichever path seemed to offer the quickest path to approval, even if it meant heaving a Hail Mary pass at the end. If patients really want to get angry at someone, they might want to take a closer look at Dendreon management — particularly CEO Mitchell Gold, who coincidentally sold off a big chunk of stock virtually the moment Dendreon shares bounced up on the positive advisory-panel vote.

Still, the patients consistently ask one question that deserves answering: Why not approve a drug that seems relatively safe, as Provenge does, and let it stand or fall in the market? While there’s a practical answer — the FDA is legally bound to ensure both the safety and effectiveness of drugs — a better response is both moral and economic.

No one wants prostate-cancer patients to die agonizing deaths. Allowing an unproven and undoubtedly expensive treatment like Provenge onto the market, however, means that its costs will be picked up by taxpayers and anyone who pays health-insurance premiums — again, in the absence of proof that it will help anyone. That seems like a bad gamble at a time when healthcare costs are already rising far faster than inflation. And since those skyrocketing costs are also boosting the ranks of the uninsured — partly because employers are scaling back coverage — you have to ask if providing an unproven treatment to a small group of cancer patients is worth the additional misery in store for ordinary people who lose or can’t get health insurance as a result.

In addition, once a treatment is available, it’s far more difficult to figure out whether it actually works or not. Patients aren’t likely to volunteer for controlled clinical trials in which they might end up receiving a dummy shot if they can be assured of getting the real thing from their doctor. While it’s still possible to compare marketed treatments to other marketed treatments, the logistics and expense can be hairy.

Patients, of course, aren’t the only ones grousing about the costs and delays that result from waiting for evidence that a given treatment works. Right around the time the FDA postponed approval of Provenge, for instance, the WSJ editorial page featured two pieces in which biotech-industry executives effectively argued for setting aside hard statistical evidence in favor of wishful thinking.

The first piece was by Richard Miller, the CEO of Pharmacyclics, a company that has been notoriously unsuccessful in proving that a drug called Xcytrin works against tumors in the brain the way it is supposed to. Miller’s complaint is that while clinical trials suggested that Xcytrin works, the data failed tests of “statistical significance” designed to distinguish actual results from random chance. Similarly, in a May 14 piece, a former FDA official named Mark Thornton lamented the day the agency postponed approval of Provenge and another cancer immunotherapy, calling it “Black Wednesday” and accusing the FDA of “kneeling before the altar of statistics.” (Oddly, the WSJ didn’t see fit to note that Thornton is currently a vice president at GenVec, a gene-therapy biotech that might also benefit should the FDA relax its statistical standards.)

The two men do have a point: The significance level required by the FDA is indeed arbitrary. The problem is that you have to set that bar somewhere, and Miller’s argument that it should depend on vague notions like “context” and “very real advances in science and medicine” is simply incoherent. (Thornton’s notion that “solid immunology science” should trump statistical significance isn’t any easier to understand.) My favorite part, though, is when Miller argues that “[s]tatistical standards, of course, should not be set aside” — this right in the middle of an article pleading with the agency to grant a statistical exemption for Xcytrin.

Such “up with patients, down with pointy-headed statisticians” sentiments have a politically conservative underpinning that isn’t hard to find. Check out, for instance, DrugWonks, a blog run by the Center for Medicine in the Public Interest. There, conservative pundit and former Manhattan Institute official Robert Goldberg criticizes the FDA’s “deadly decision to delay Provenge” and its advisors’ dedication to the “probabalistic priesthood” in language virtually identical to that used by Miller and Thornton — almost as if they’d all been reading from the same script. Ultimately, it’s hard to escape the impression that these folks are less concerned about patients than they are about the freedom to market drugs without all that pesky FDA interference.

On the other hand, every drug-safety scandal that erupts over treatments like Vioxx and Avandia helps make the case for the importance of good medical evidence. Among other encouraging signs that evidence-based medicine is slowly getting some traction are these articles on a House bill that would provide $3 billion for evidence-based studies by the federal Agency for Healthcare Research and Quality. AHRQ has fallen on hard times over the past decade, a trend that might be about to reverse itself. More on that in a future post.

The Senate passed a bill that requires the FDA to monitor the safety of drugs more rigorously once they’re on the market, but punted on other proposals that would have allowed the legal import of drugs from other countries and bolstered the agency’s ability to regulate drug advertising aimed at consumers.

The drug-safety measures incorporate many suggestions from an Institute of Medicine report last year that critiqued FDA’s ramshackle efforts to track side effects and other problems associated with drugs such as Merck’s painkiller Vioxx once they have run the regulatory-approval gauntlet. The bill would more than double the staff assigned to the FDA office responsible for monitoring drug safety, establish a computerized registry to track drug side effects, and allow the agency the power to order new clinical trials, limit drug distribution and change drug labels if problems emerge (the FDA must now negotiate such changes with a drug’s maker). It requires drugmakers to mention safety problems clearly in their advertising and orders the federal government to establish a public database of drug-related clinical trials that should, in principle, make it easier to detect drug-safety problems in the first place.

All of these measures were wrapped together with a renewal of PDUFA — the law that authorizes the FDA to collect user fees from industry that fund roughly half of its drug-review apparatus. That law expires Sept. 30, so the reauthorization bill — considered “must pass” legislation since the FDA would have to make drastic staff and operations cuts if it lapses — has become a vehicle for a variety of reform measures. Many of them, however, fell by the wayside as the bill moved through the Senate. The bill now heads to the House, which hasn’t yet taken up its own user-fee renewal measure.

Most of these safety-related changes are long overdue, despite the uncertainty they may now create for biotechnology companies. Concerns about drug safety are real and rising — witness what Amgen is going through with its anemia franchise — and in the end it will be better for industry if a more safety-minded FDA has the hard data and fine-tuned policy tools it needs to make nuanced judgments about future safety risks. Of course, it’s almost impossible for a bill like this to pass without at least one completely symbolic measure — here, I’d nominate the doubling of fines for drug-safety violations to a piddling $2 million — not to mention unrelated constituent-service items that legislators just can’t seem to resist. (For an amusing — or horrifying — list, check out the WSJ Health Blog.)

For more on the Senate PDUFA bill, see the NYT, the WaPo, the LAT, and the WSJ.

No nukes in lymphoma treatment – Two innovative biotech drugs that target tumor cells for destruction by tiny radioactive particles are struggling in the marketplace, in part because cancer doctors are simply too specialized to make proper use of them. The drugs — Zevalin (pictured at left), from Biogen Idec, and Bexxar, now produced by GlaxoSmithKline — consist of bioengineered antibodies that carry fragments of radioactive material directly to lymphoma tumors in the bloodstream, where the localized radiation can kill cancer cells with fewer side effects than traditional radiation or chemotherapy.

Although both drugs seem to work well, fewer than 10 percent of eligible lymphoma patients receive either one, the AP reports. One main reason: Oncologists don’t usually work with radioactive materials, and so must send patients to nuclear-medicine specialists instead, something many are loathe to do. Demand for the drugs is so anemic that Biogen Idec announced in December that it will try to sell off Zevalin to another company. It’s an interesting tale of how some innovations can fall completely flat when they don’t neatly fit modern medicine’s specializations.

Vaccinating infants — or cows — for E. coli – Those are two possible steps that might protect people from food poisoning by the bacterium Escherichia coli, which was responsible for two major outbreaks last fall, one involving bagged spinach and the other contaminated lettuce served in chain tacos. At the moment, doctors have few options for treating E. coli-related illness, but have begun considering ways to vaccinate children against the bug and to test possible therapies. Canada last year approved an agricultural vaccine for cows that can limit, but not eliminate, E. coli in the animal’s manure. (Cows and their waste are the primary source of the microbe.) The NYT has the story.

New eggs from old ovaries – In a fascinating fertility-medicine development, women can now have small strips of their ovaries frozen, then thawed and re-implanted years later to produce youthful-seeming eggs — even if they have already reached menopause. The technique is most commonly used when medical treatments such as chemotherapy threaten a woman’s fertility, although some women simply hope to improve their odds of bearing children in later years. Check out the WSJ story here.

Ballooning costs of biotech drugs – In five years, biotechnology treatments could account for a full quarter of all prescription-drug spending, according to a study by pharmacy-benefits manager Express Scripts. Spending on biotech drugs is rising far more quickly than for traditional pharmaceuticals, largely because many biotech drugs tend to be vastly more expensive, imposing costs that can range into the tens of thousands — or even hundreds of thousands — of dollars per year. Overall spending on biotech drugs rose 21 percent in 2006, compared to a 5.9 percent increase for traditional pills. By 2010, the company predicts, biotech drug spending will rise to $99 billion and will account for 26 percent of all drug costs, almost double the $54 billion spent in 2006. New drugs for cancer, arthritis and other inflammatory conditions are expected to account for the bulk of that growth. (Hat tip: Reuters, via the San Diego Union-Tribune.)

Additional signs of life among early-stage biotechs – Solace Pharmaceuticals today said it raised $15 million in an early venture round, providing further evidence that investors’ interest in younger biotechs may be perking up. The Boston-based company is developing new pain treatments; its investors include Polaris Venture Partners and InterWest Partners.

Doctors and sales reps, entangled again – A federal court struck down a New Hampshire law that barred the sale of physicians’ prescribing patterns to drug companies, information that drug reps use to tailor their approach to particular doctors. According to the NYT account, the decision may impact several other states that have considered similar laws. Separately, the NYT reports that some doctors are starting to just say no to free drug samples.

Prospects for “biogeneric” legislation may be dimming – Several reports suggest that momentum behind the push to allow cheap generic-style competitors to expensive biotech drugs is slowing, largely because the Senate failed to include the bill in a package of proposed laws that include various FDA reforms and renewal of the program under which drug-industry fees help pay for drug approvals. The biogenerics bill may still move separately, but the conventional wisdom seems to be that its odds were much better as part of the FDA package. The NYT has more on that FDA-reform package here.

(Note: This item has been copied over to the Life Sciences page from its original location on the VentureBeat main page. To view it in its original context, with comments, click here.)

A second legislative fight for the biotech industry is shaping up in Washington over whether to give the Food and Drug Administration authority to approve “generic” versions of biotechnology drugs whose patents have expired.

Measures that would grant FDA that authority, introduced separately in the House and Senate, are billed as a natural cost-saving measure by supporters. They note the high cost of many biotech drugs and the fact that several best-sellers are expected to go off-patent over the next few years. To biotech’s biggest companies and their lobbyists, however, the effort could jeopardize public safety and the incentives that lead companies to spend vast sums in search of new drugs in the first place — at least unless the copycat products are required to go through the same arduous and expensive clinical trials as their brand-name counterparts.

Here, the industry relies on an argument that is one part science and one part misdirection. Biotech drugs generally consist of large, complex proteins that are much more difficult to understand than the relatively straightforward active chemical ingredients in traditional pills. The industry argues that it’s impossible to analyze copycat biotech drugs thoroughly enough to know whether or not they’re identical — or at least close enough — to a name-brand version. Which, of course, leads to the demand that copycat biologics run the same human-trial gauntlet as name-brand drugs, a requirement that might run up development costs so high that a “generic” biotech drug wouldn’t necessarily be any cheaper than its rival.

The problem here is that some biotech-drug proteins aren’t so complex as to defy analysis. The FDA, for instance, already approved a copycat version of human growth hormone called Omnitrope a year ago, after a variety of laboratory and limited human tests allowed FDA scientists to determine that it was “highly similar” to its name-brand cousin. That sort of testing isn’t possible for all biologic proteins, but as analytical laboratory technology gets better, so will the FDA’s ability to correctly assess the similarity of even complex protein drugs. Last month, in fact, FDA Deputy Commissioner Janet Woodcock testified before Congress that the agency already has the skills to make those assessments in some cases. Since the bills in question simply give the FDA the authority to authorize copycat versions of biotech drugs when the evidence warrants it, it’s hard to see what all the shouting is about.

Except, of course, that this fight — like most such Beltway brawls — is at heart about money. Unlike Big Pharma, which has to brace itself for generic competition every time a billion-dollar drug approaches the end of its patent lifetime, biotech companies face little threat of pricing pressure even when patent protection lapses on their cash cows (such as Amgen’s Epogen, a version of the erythropoietin molecule pictured above). Given that annual costs for many best-selling biotech drugs run into the tens of thousands of dollars — even hundreds of thousands in some cases — the green at stake is truly astonishing.

As for the innovation argument, it helps to remember that patents are limited, artificial monopolies created for public-policy reasons that are written into the Constitution itself. If innovation in the biotech industry really depends upon perpetual monopolies over incredibly expensive drugs — well, let’s just say that this is not an argument you’re likely to hear explicitly from a biotech representative any time soon.

A second legislative fight for the biotech industry is shaping up in Washington over whether to give the Food and Drug Administration authority to approve “generic” versions of biotechnology drugs whose patents have expired.

Measures that would grant FDA that authority, introduced separately in the House and Senate, are billed as a natural cost-saving measure by supporters. They note the high cost of many biotech drugs and the fact that several best-sellers are expected to go off-patent over the next few years. To biotech’s biggest companies and their lobbyists, however, the effort could jeopardize public safety and the incentives that lead companies to spend vast sums in search of new drugs in the first place — at least unless the copycat products are required to go through the same arduous and expensive clinical trials as their brand-name counterparts.

Here, the industry relies on an argument that is one part science and one part misdirection. Biotech drugs generally consist of large, complex proteins that are much more difficult to understand than the relatively straightforward active chemical ingredients in traditional pills. The industry argues that it’s impossible to analyze copycat biotech drugs thoroughly enough to know whether or not they’re identical — or at least close enough — to a name-brand version. Which, of course, leads to the demand that copycat biologics run the same human-trial gauntlet as name-brand drugs, a requirement that might run up development costs so high that a “generic” biotech drug wouldn’t necessarily be any cheaper than its rival.

The problem here is that some biotech-drug proteins aren’t so complex as to defy analysis. The FDA, for instance, already approved a copycat version of human growth hormone called Omnitrope a year ago, after a variety of laboratory and limited human tests allowed FDA scientists to determine that it was “highly similar” to its name-brand cousin. That sort of testing isn’t possible for all biologic proteins, but as analytical laboratory technology gets better, so will the FDA’s ability to correctly assess the similarity of even complex protein drugs. Last month, in fact, FDA Deputy Commissioner Janet Woodcock testified before Congress that the agency already has the skills to make those assessments in some cases. Since the bills in question simply give the FDA the authority to authorize copycat versions of biotech drugs when the evidence warrants it, it’s hard to see what all the shouting is about.

Except, of course, that this fight — like most such Beltway brawls — is at heart about money. Unlike Big Pharma, which has to brace itself for generic competition every time a billion-dollar drug approaches the end of its patent lifetime, biotech companies face little threat of pricing pressure even when patent protection lapses on their cash cows (such as Amgen’s Epogen, a version of the erythropoietin molecule pictured above). Given that annual costs for many best-selling biotech drugs run into the tens of thousands of dollars — even hundreds of thousands in some cases — the green at stake is truly astonishing.

As for the innovation argument, it helps to remember that patents are limited, artificial monopolies created for public-policy reasons that are written into the Constitution itself. If innovation in the biotech industry really depends upon perpetual monopolies over incredibly expensive drugs — well, let’s just say that this is not an argument you’re likely to hear explicitly from a biotech representative any time soon.