Stakeholders in Consumer Genomics, Read This

Noting a flurry of recent commentaries in peer-review journals, our February Science Matters column in START-UP (link here, free access) discussed how the personal genomics company 23andMe has accelerated the consumer genomics debate through its dust-up with FDA over the lack of evidence and documentation supporting its Personal Genome Service, which FDA warned falls under its definition of a medical device.

The commentaries, in Nature, NEJM, and JAMA are a reminder that genomics is rapidly becoming incorporated not only into the clinic, but into everyday life. It is forcing FDA and other agencies to take a stand on critical technical, legal, and ethical issues, which will influence the strategies of medical diagnostics and pharmaceutical companies as well as labs performing tests directly for the consumer. As we wrote, those regulatory decisions should be made with the awareness that at some point, barriers to consumer access to these data will come down.

In researching the column, we were directed towards a draft report by the Presidential Commission for the Study of Bioethical Issues, “Consuming Genomics: Regulating Direct-to-Consumer Genetic and Genomic Information.” Its authors call the 86-page document “one of the first to analyze the effect of the 23andMe Warning Letter on the industry, to focus on the bifurcation of genetic interpretation and information as an independent medical device, and to analyze future regulatory approaches available to FDA.” Forthcoming in the Nebraska Law Review, a draft is available here.

The report provides a clear, detailed, up-to-the-moment summary of the the regulatory, ethical, and legal issues around DTC genetic testing. It also lays out what FDA considers a laboratory-developed test, what it considers a clinical device for commercialization, what it considers a research exemption, and why. It's a great read for those of us trying to keep straight FDA's thinking on LDTs, its jurisdiction, and the possible dividing lines between regulated and unregulated products, as well as the history of the consumer genomics field. -- Mark Ratner

Note: This post originally stated that the report is from the Presidential Commission for the Study of Bioethical Issues. The authors, Kayte Spector-Bagdady and Elizabeth Pike, work for the Commission. However, the report was written in their personal capacities.

Tweeting Around Europe's DTC Ban: Bayer Named and Shamed

A press release about a new drug launch is ok; a tweet isn't.

That appears to be the conclusion of a months-long saga over drug firms' -- in particular Bayer UK's -- use of social media to allegedly 'promote' its drugs in Europe, where DTC advertising remains a no-no.

Never mind that tweets don't respect geography. Bayer will be named and shamed in various medical journals (The Nursing Standard, 17 Aug; BMJ and The Pharmaceutical Journal, 20 Aug.) for tweeting about new UK drug launches earlier this year, according to the PMCPA, which administers the UK drug industry's (the ABPI's) Code of Practice.

The German conglomerate in March tweeted on the launch of "first and only melt-in-the-mouth erectile dysfunction treatment" (Levitra), following a similarly promotional tweet the year before about multiple sclerosis drug Sativex, according to the Digital Pharma blog.

The company claimed at the time that it was issuing only 'factual and non-promotional' information, linked to approved press releases. It also said at the time that guidance from the PMCPA on the use of social media was 'far from clear'.

The guidance has been updated to include what amounts to a ban on tweeting about prescription medicines, however. But Bayer would not comment specifically on whether it now found the guidelines clearer, saying only that "as a member of the ABPI, Bayer recognises the industry Code of Practice and, as a company, is absolutely committed to compliance with all laws, regulations and good business practices."

Of course it is. And that -- could we call it contrition? -- is the effect that the watchdogs wanted this naming game to achieve. Any companies perceived as attempting to circumvent Europe's DTC ban via social media networks like Twitter had better think again, or risk being brandished as, per the ABPI code, 'bringing discredit upon' the pharmaceutical industry.

This case will almost certainly fuel the ongoing debate around a stalled piece of EU legislation attempting to harmonize and update the region's policy on information to patients (what's allowed, what isn't).

Meantime, notwithstanding the name-and-shame ads, we bet that the @bayerukireland twitter account may have picked up a few more followers-- if only to keep tabs on them. Whatever its intention, Bayer did effectively circumvent the DTC ban in the case of Levitra: plenty of non-medical professionals know what's available as melt-in-the-mouth.

image by flickrer fanie used under creative commons

You Can Be A Star!

We at the IN VIVO Blog know this is a tough time for plenty of folks in biopharma companies (almost as bad as it is in journalism) and we always try to do what we can to help people who are between jobs. So, when the following casting call came across our desks, we figured we should open it up to as many possible candidates as possible.

Here is it is:

[AGENCY NAME] is seeking talent for a NATIONAL SAG commercial for LIPITOR. We are seeking the following types of talent. Actors and non-actors are welcome to apply:

· Males who are 50-65 years of age
· ALL ethnicities
· Currently taking LIPITOR for at least 6 months
· You do NOT have to have had a heart attack/cardiovascular event
· We are only looking for NEW talent that have not already auditioned for this project in any market/with any other casting company (your tape is already on file).

If you would like to be considered, please send an email with your headshot/snapshot.

No Phone Calls Please. Thank you.

If you think you meet the criteria, drop us a line and we'll provide you the contact details--though we MAY ask you to write up your experience too ... and we don't pay as well as Pfizer...

A "Sophie's Choice" for Pharma in Tax Policy: R&D or Marketing?

The tax write off available for pharmaceutical marketing costs has been a popular political target for industry critics for more than 20 years—and all the moreso in the era of broadcast direct to consumer advertising. Many in Congress want to ban DTC ads outright; that almost certainly won’t pass First Amendment scrutiny, so making advertising more expensive by changing the tax code is an appealing alternative.

Still, while it makes a good talking point, advertising critics have never succeeded in pushing the idea through to enactment.

Now the Democratic leadership in Congress is considering a new twist, a proposal to give pharma companies a choice: write off R&D costs or write off marketing costs. Not both.

That, according to Polsinelli Shugart public policy group Chair Jim Davidson during his update to the DTC National Congress April 15, was an idea offered by former Rep. Rahm Emanuel during a closed door meeting with some advertising types last year.

The idea sure sent a ripple through the 400 or so pharma, ad agency and media attendees at the DTC Congress.

Emanuel has since left Congress to serve as chief of staff to President Obama, which does nothing to blunt concerns among advertisers about the potential for the tax policy proposal to slip into legislation this year, especially in the context of finding new revenues to cover costs of expanded health care coverage. (Read more about Emanuel’s recent statements here.)

Coalition for Healthcare Communications Director John Kamp noted the threat of Emanuel’s proposal, describing it as presenting a “Sophie’s choice” to industry by asking, in effect, whether companies love their marketing departments or their R&D organization more. It is a classic divide-and-conquer maneuver, Kamp says, since it is sure to exploit the tensions that already exist within pharma companies over that very question.

“Think about your own companies,” Kamp told the brand managers in the audience.

Well, it certainly got us to thinking…and quickly got us thinking that maybe this “Sophie’s choice” wouldn’t be all bad.

Now, let’s be clear: biopharma companies will fight this proposal, as will advertising and media companies. And, if history is any guide, they will win. Pharma, in particular, has a good track record in working the intricacies of tax policy. No reason to expect a different outcome here. Nor do we seriously think pharma should support a tax hike on itself in any event.

It is just that this could be a case where a policy threat would force a healthy business adjustment.

The new tax policy would, in effect, force pharma companies to choose between a reduced return-on-investment from their R&D or a reduced RoI on marketing, since the elimination of the tax deduction in effect amounts to a reduced return on the dollars devoted to the affected activities.

So the first step would be to force senior management to take a stand on which actually delivers a better RoI in the first place.

In some cases, it is easy. Most biotech companies, for instance, only wish they had marketing costs to write off, and even those that do wouldn’t have too much trouble choosing to keep writing off R&D. On the other hand, “specialty” companies like Forest or Ovation would surely want to write off marketing costs, since they tend to in-license late-stage projects rather than shoulder the full R&D burden themselves.

But what would Pfizer do? The company spends billions on R&D and billions on marketing, and so could ill afford to accept higher taxes on either front.

Surely one option would be to divide into smaller companies that more clearly fit the biotech (R&D-first) or specialty (commercial-first) models. That happens to be exactly what some of us have been suggesting for a long time now.

Indeed, one way to view the Pfizer/GlaxoSmithKline HIV partnership is as a baby step (or maybe a toddler step) in that direction. Glaxo/Pfizer HIV Inc. would surely choose to keep its R&D deduction. (As would, presumably, a stand-alone Pfizer oncology unit.)

Pfizer itself, on the other hand—if it indeed continues to consolidate towards a GE style health care marketing colossus—would probably end up protecting the deductibility of its marketing costs. In fact, its hard to see how R&D fits long term in that GE model anyway. (You can read coverage of Roger Longman’s latest take on this topic in “The Pink Sheet” here.)

See how fun it is to play what ifs?

And that’s the point. Pharma companies are right to oppose the policy, but there is surely value in playing out this “Sophie’s choice” anyway. It may turn out to be good business for pharma to focus on one side or the other of the great pharma divide between R&D and marketing, even if Congress doesn’t force that choice upon them.

More Information to Patients in Europe? Not Really

The industry dared to be optimistic, but was disappointed. Drug chiefs were hoping for more opportunities to communicate directly with patients in Europe, as part of much-needed change to marketing and selling models. (Read more on that in the forthcoming issue of IN VIVO).

Sadly, the European Commission's pharmaceutical legislation package, presented today to the Council of Ministers and European Parliament, "doesn't make a huge difference" to information provision in the UK, according to Richard Barker, Director General of the Association of the British Pharmaceutical Industry.

The proposals allow information which "does not go beyond the elements of the summary of product characteristics," plus "related information about non-interventional scientific studies," according to EC documents published today. And this information can be disseminated only via specialist publications and websites--no active distribution allowed. "It's a pull-model," summarized Barker--in other words, just about as far from DTC as it could possibly be.

Not that DTC was what the industry was after; it knows that doesn't work particularly well anyway (and some CEOs apparently hate it with a vengeance). But a little more freedom to communicate might have been nice. So would more clarity on whether information must be vetted pre- or post-dissemination: a summary memo released prior to the full documents states that "in general information will be subject to monitoring after it has been disseminated."

The full text, though--and what was picked up in this Reuters piece--says that "monitoring should be based on the control of information prior to its dissemination, unless the substance of the information has already been agreed by the competent authorities or if there is a different mechanism in place to ensure an equivalent level of adequate and effective monitoring." [our ital.]

Hmm. Assuming that last bit means that pre-vetting can be avoided (communication may prove highly burdensome if not) the proposals at least "don't take us backwards," adds Barker. In the UK, limited information is already available to patients via sites like medicines.org.uk. Like anything coming out of the EC, the package is a compromise between opposing positions. UK and Scandinavian attitudes to patient information contrast with that of France, for example, which remains highly sensitive to any sort of direct channel between manufacturer and patient.

Patient information is just one part of this story. Pharmacovigilance and counterfeit drugs feature too--though the branded sector missed out on a complete ban on the re-packaging of pharmaceuticals, which would have crippled parallel traders. (They rely on this to re-sell drugs bought in low-priced country A to higher-priced country B.) The finalized plan, unlike earlier drafts, states explicitly that "re-packaging remains possible"--a big nod in the direction of the parallel traders' lobby.

This set of legislation is tabled as a "renewed vision" for the European drug sector. But for Barker, it represents only a very small step, albeit in the right direction. "We need to go well beyond these measures to give a real boost to an industry's that's packing up and leaving Europe," he warns.

It's not enough to "launch reflections," as the EC is doing, on ways to improve market access and boost R&D. Aggressive action is needed if Europe isn't going to slide further behind, in particular given the rise of investment in developing markets. But aggressive action isn't what the EC does--or can--provide.

Burns Lambasts DTC

What's the single worst event to have happened to the US pharma industry? You or I might come up with a list of a dozen or more candidates. For Bill Burns, CEO of Roche’s pharmaceuticals division, it's direct-to-consumer (DTC) advertising.

Speaking at the FT Global Pharmaceutical and Biotechnology conference in London yesterday, Burns vigorously decried DTC as having led to a “lower understanding of the industry by the US population.” Citing the withdrawal of Merck’s highly-DTC’d Vioxx, he declared that “people in the US feel that the industry has let them down. There’s a lack of credibility.”

He’s right, of course (though DTC, if important, isn’t the only issue behind the industry’s image problem). And Burns isn’t first to outline DTC’s limitations: the rest of the industry recognizes, too, that this form of advertising isn’t raking in the returns it used to. Self-imposed restraint on the more overt campaigns began a couple of years ago amid political uproar over erectile dysfunction drug ads (see this and related stories in The RPM Report).

But Burns’ belligerent anti-DTC outburst must surely be one of the loudest and most explicit yet. Perhaps as a result it left a lingering whiff of higher-moral-ground hypocrisy under some noses in the room. “That might be his line here [in the UK] but it’s not what Roche executives follow [in the US],” noted an SVP from a rival firm.

Still, Roche isn’t exactly top of the DTC spending ranks: it sells mostly specialist drugs, after all. And DTC ads probably did more to batter rather than boost sales of one exception, fat-buster Xenical--are you thinking of oily-stools yet?

We know where Burns is coming from. But we, sadly, find it harder to imagine US public perception approaching where he’d like it to go: the gilded, pharma-friendly society in Roche’s native Switzerland, where “seven out of ten people are proud of the industry’s achievements.”

Not that Burns was claiming Switzerland—or Europe—had the answers, though. There, it’s the other extreme, “we can’t even talk to patients. That’s wrong, too.”

Pharma executives expect Europe’s ban on DTC to ease—possibly through a set of wider pharmaceutical legislation proposals that the European Commission was due to publish this quarter. The notion of allowing companies to pass on information directly to patients “is now more acceptable to European authorities,” claimed AstraZeneca’s CEO David Brennan at the same meeting. “It’s a question of when, not if, in my opinion,” he concluded.

But the 'what' won’t be drug-ads in bus-stops, on buses and on TV. If it’s anything at all (the EC package has been delayed indefinitely), it’ll likely be more general information on recognizing particular diseases and how to deal with them. No drug names; nothing that will whip up quite the same fury as US-style DTC.

image from flickr user lecourrier used under a creative commons license

A Wolfe In Wolf's Clothing

No one expects Sidney Wolfe to sit on his hands at an FDA advisory committee meeting, and at his first outing as a permanent member of the Drug Safety & Risk Management Advisory Committee, he didn’t disappoint.

During a two-day meeting last week to consider the approvability of two abuse-resistant pain medications, Wolfe took a few minutes to grouse about one of his favorite topics, direct-to-consumer advertising, and specifically Purdue’s $600 million fine over misleading advertising and promotion of OxyContin. Here’s what he said:

“The gorilla, or donkey or elephant in the room is advertising and promotion. If OxyContin was that dangerous ... maybe it would be off the market. The number-one culprit—and the number two, three, four, five, six and seven—and the reason for the $650 million penalty was misleading advertising and promotion.”

Wolfe also couldn’t help but take a dig at the two products up for approval decisions: Alpharma’s abuse-resistant form of morphine, Embeda, and Pain Therapeutics’ abuse-resistant form of oxycontin, Remoxy. (Neither drug won kudos from advisory committee members; you can read our coverage on those meetings here and here).

“Any company that wants to develop...a product that is novel and has significant benefits over existing products—something I haven’t seen over the last couple of days—is going to spend a huge amount of money advertising and promoting,” Wolfe said.

It’s true that advisory committee members sometimes go off the reservation on issues like pricing and insurance coverage. And we don’t necessarily disagree with what Wolfe is saying—we’ve also suggested that industry take a hard look at DTC advertising and whether it’s really worth all the potential political and legal headaches.

But for companies with products slated to go before Drug Safety & Risk Management Advisory Committee—and given the ubiquitous nature of REMS, there will be many—those are the type of comments to expect out of Wolfe. In the case of Embeda and Remoxy, his comments only reinforced the direction the committee was headed in anyway. That may not be the case next time.

What’s next for Wolfe? The next meeting of the Drug Safety & Risk Management Advisory Committee is two-day discussion on the safety of long-acting beta agonist inhalers in December. That’s big-name products like GSK’s Advair, AstraZeneca’s Symbicort and Schering-Plough’s Foradil. Stay tuned.

While you were winning/losing some

This weekend saw two major sports upsets, though neither was as shocking as the deep six of the global financial markets just a week ago. At last, the US finally won back the Ryder Cup, ending nine years of European domination; meanwhile, NFL fans not rooted in the six New England states cheered as the Miami Dolphins absolutely obliterated the Patriots defense with an annoyingly-simple-yet-hard-to-beat "Wildcat play" that snapped the Patriots 21 straight regular season wins. (The last loss was Dec. 10, 2006, coincidentally against the Dolphins.)

No financial crisis will slow down the consolidation of the generics pharmaceutical companies, according to this report. Of course, we've been reporting on the rise of generics for some time. At the same time, we're seeing a slowdown of the overall M&A market for pharma companies. (Check out the extensive report here or in this month's Start-Up.) Nevertheless, the Royal Bank of Scotland recorded a level number of buyouts this year, valued at more than $25 billion, an 80 percent increase over last year. Teva Pharmaceuticals' $9 billion buyout of Barr Pharmaceuticals certainly helped drive up that number, and Teva's chief executive for North America, Bill Marth, says more deals may be following the Barr buy. "It doesn't leave us in a position where we won't do more acquisitions that are complementary, it will just change the focus of those acquisitions," Marth told reporters Friday.

Speaking of generics, Ranbaxy, Indian's largest drugmaker and a recipient of a smackdown by the FDA, has recruited one-time GOP presidential (and vice presidential?) candidate Rudy Guiliani to take on its fight. The former Hizzoner will push to lift the ban the FDA put on more than 30 Ranbaxy medicines after finding deficiencies in Ranbaxy's plants. The company says the FDA's concerns are baseless. The Economic Times says other Indian pharmaceutical companies aren't overly concerned about selling in the U.S.

It ain't Lehmans Brothers, but things aren't looking well for Atherogenics, according to Pharmagossip, which linked to an article from the Atlanta Business Chronicle. Noteholders in the company filed a petition to put the company into Chapter 7 bankrupty.

Happy Birthday to Bayer Corp. The U.S. subsidiary of Bayer AG marks its fiftieth year in the US, according to an article in the Pittsburgh Post-Gazette. The paper had a sit down with Gregory Babe, who is to become the first American-born executive to head the subsidiary.

Direct-to-Consumer advertising continues to draw fire. The Guardian reports that the British Medical Association and the Royal College of Physicians are among nine medical organization to opposed the introduction of direct-to-consumer medicine. The group's contend that the NHS's eleven billion pound annunal drug cost would skyrocket if pharma comapnies could pitch their product directly. Meanwhile, on this side of the Atlantic, the FDA heard from two physicians who want the FDA to expand its oversight of direct-to-consumer ads to include medical devices. The docs--an orthopedic surgeon and cardiologist--who say drugs and devices should stand on equal footing when it comes to DTC ads, therefore putting the devices under greater scrutiny.

Viagra and Mad Men: A Match Made in Heaven...

Forget "wild man." Viagra may have found the perfect marketing tie-in, at least on our local cable provider in DC: as the sponsor of "On Demand" replays of AMC's Mad Men.

If you are not a fan, Mad Men is a show about an advertising firm circa 1960 (Ad men+ Madison Avenue=Mad Men). It revels in depicting the corporate culture of that era: three-martini lunches, chain smoking executives, and sexual harassment as office sport.

What better vehicle to promote the quintessential product of the direct-to-consumer advertising era than a program about the invention of Madison Avenue itself?

The placement of Viagra on the season two premier was even more perfect. The episode in question, entitled "For Those Who Think Young," is set on Valentine's Day. And the ad break came after a pivotal scene. Here is how the episode summary describes the action:

Upstairs in their hotel room, Betty emerges from the bathroom, in heels, stockings, and a bustier. "Wow," says Don (pictured above), although later he can't pull the trigger in the midst of lovemaking. "I wish you'd just tell me what to do," Betty says afterwards. They order room service and watch Jackie Kennedy’s televised White House tour.

Cue "Viva Viagra."

There is one other reason why this sponsorship may be perfect. Mad Men's entertainment relies on the almost over-the-top behavior of its ad men--but it also makes unflinchingly clear that the world was most definitely not a better place in those "good old days."

We can't help but think that one day industry may look back on broadcast TV ads in the same light. It seemed fun at the time, but was it really the right way to do things?

While You Were Saying Goodbye to Summer

going, going, gone.

Outta here like a Ryan Howard shot to deep right field, vanished like Keyser Soze, Summer 2008 is now just a memory. Hey, at least football season has begun, right? Below, our roundup of what you might have missed while enjoying that last BBQ of the season.

• European Society of Cardiology: News came thick and fast out of this annual meeting in Munich. The results of a potentially important study of stents vs scalpels in treating clogged arteries are in, and surgery has come out on top. Lilly and Daiichi's prasugrel got a boost in diabetics prior to its 26th September FDA deadline. An analysis of the previously released Triton-Timi 38 trial showed that prasugrel was more effective than standard-of-care clopidogrel (Plavix) in that patient population, reports Reuters. Pronova/GSK's Omacor (fish oil) met both primary endpoints in a Phase III outcomes study in patients with heart failure, who were 9% less likely to die than patients given placebo. AZ's Crestor didn't fare as well in a similar population. Finally, Bayer said it would speed up development of rivaroxaban--putting a little extra pressure on Pfizer/BMS, whose rival candidate apixaban hit a snag last week, as we wrote about here. For more news out of the meeting, click here.
• Shionogi & Co. is the latest in a pretty long line of Japanese pharmaceutical companies buying up cheaper American firms to help expand into western markets. Shionogi bought Sciele Pharma for $1.1 billion ($31/share, a 61% premium to the stock's previous close) plus the assumption of $325 million in debt, the companies announced on Monday. Atlanta-based Sciele had revenues of more than $382 million in 2007, and specializes in women's health, cardiovascular disease, diabetes, and pediatrics. For more on Japanese Pharma appetites, see here, and look for a feature on these trends in an autumn issue of IN VIVO.
  
• Oncology expert Prof. Karol Sikora of CancerPartnersUK diagnoses the ills of the country's NHS and writes this prescription in The Sunday Times: "Radical structural change to the NHS is vital. Competition and choice drive up quality and access, so leading to greater value, just as we’ve seen in other consumer areas such as mobile phones, budget airlines and the high street. Sensible incentives linked to performance and outcomes are essential. Drastic reform, not more money, is now needed."
• Novacea, which begun a strategic review in May after Schering-Plough canceled an alliance around its entered an agreement to merge with Trancept Pharmaceuticals (nee TransOral Pharmaceuticals, click here for our admittedly old 2003 profile of the firm). The latter company, a privately-held specialty pharma that specializes in tweaking the pharmacokinetics of CNS compounds, has raised more than $70 million in venture funding but--surprise, surprise--has been unable in this climate to tap the public markets. If investors buy into this reverse merger, TransCept backers will hold 60% of the combined company, which, the companies say, will have enough cash to pursue FDA approval for and launch its Intermezzo lozenge formulation of the insomnia drug zolpidem (the now-generic Ambien).
• Lipitor ads are back after six months off the air, but you mean nasty bloggers won't have Dr Jarvik to kick around any more! According to the WSJ, Jarvik's out and heart attack survivor John Erlendson is in. What are the odds that he's a rower?
• In the latest installment of its A1 "The Evidence Gap" series, The New York Times asks why more than three million people still take Vytorin/Zetia every day, and notes that some prominent cardiologists are now calling for it to be taken off the market.
  
• The Guardian adds up the challenges facing Big Pharma and, well, that's pretty much it. Would have been nice to see some answers in there too.
  
• Speaking of The Guardian, Ben Goldacre's Bad Science (the book) is on shelves now (at least in the UK). Go on, buy one. And if you haven't already, click the link to his web site in our blogroll to the right to get a preview.
  

It's Not DTC, It's HBO

GlaxoSmithKline Consumer Healthcare and its team that promotes the over-the-counter weight loss drug alli have to be rooting for HBO’s recently announced pilot “Fat Sells” to make it to the air.

The cable network will air “Fat Sells” (get it?), a “one-hour family drama set in the world of the $46 billion herbal supplement weight loss industry,” with Academy Award winner Forest Whitaker to executive produce.

"Everyone is looking for that Magic Pill to change their lives ... We're taking a world not regulated by the FDA and breaking it wide open," says co-creator Dave Broome.

According to a report from Variety, the story “will center on the head of a weight loss behemoth (and his family) and how his life starts to unravel when the FDA begins investigating the company's claims.”

We can only hope the show can even begin to capture the excitement of a real-life FDA inspection.

Depicting weight-loss supplements as being sold as “magic pills” fits right in with Glaxo’s pitch for alli, our colleagues at “The Tan Sheet” report here. But we’re predicting we won’t see any product placement.

Glaxo, which launched alli (an Rx-to-OTC switch of orlistat, Roche’s Xenical in the prescription market) in 2007 has marketed the drug as part of a program that includes lifestyle changes such as diet and exercise. Glaxo positions alli as as “the only FDA approved” OTC weight-loss product, and an alternative to products in the supplement market that do not have to go through pre-market approval and that make more aggressive weight-loss claims.

In fact, in a move back in April that would take a large number of competitors off the market if successful, Glaxo filed a citizen petition in May asking FDA to require pre-market approval for supplements making weight-loss claims. Read about that here.

Supplement firms likely won’t be happy if Fat Sells airs, considering creator Broome, also an executive producer, has already called it an unregulated industry, an impression widely repeated in the press, and one that companies and trade groups are constantly trying to correct. And from the description of the show, it sounds like the firm depicted will be exactly the kind of company that mainstream supplement industry members have been working hard to distance themselves from, via self-regulation and public relations efforts.

On the other hand, if the show is the next “Six Feet Under,” supplement firms –and hopefully FDA – could see the same kind of uptick in job applicants that the funeral industry saw from that show.

Meanwhile, we’ll be here trying to pitch HBO some follow-on hits from the exciting world of FDA-regulated products. Keep an eye out for “The Detailers,” “Hoodia Love” and “GMPs: Miami.”

--Christopher Walker

Viagra for All: The Political Backlash Continues

Interesting item in the National Journal that caught our eye: the Congressional vote in 2005 to cut off federal funding for erectile dysfunction therapies has become an issue in the Missouri governor's race.

Rep. Kenny Hulshof, one of the candidates vying for the Republican nomination in Missouri, was among the minority who voted to continue paying for Viagra and the other ED therapies in Medicaid and Medicare. State Treasurer Sarah Steelman is using that vote against him, including in this campaign ad.

As we wrote at the time of the vote, the debate over federal coverage of Viagra is more than a slap in the face to the companies in that market. It is also an object lesson in the consequences of the backlash against direct-to-consumer advertising, as well as the impact of Congressional meddling in federal coverage policies now that pharmaceuticals are included in the Medicare program.

Three years later, the political potency (no pun intended) of the issue is undiminished. And Big Pharma's reputation continues to be intertwined with the ED market to an extent that should make almost everyone uncomfortable.

Bear in mind that these are two Republican candidates, neither of whom is defending the proposition that taxpayer money should support the ED market. As the Journal reports, Hulshof is fighting back against Steelman by arguing that she also voted to support Medicaid funding for Viagra at the state level.

Was it really less than a decade ago that Bob Dole was doing commercials on behalf of Pfizer about ED, and effectively defining the market as medical--not recreational? Dole, we think, is still a Republican hero in the heartland. Of course, he is from Kansas.

The Heat is On...The Hill

It may be springtime in Washington, but things just keep heating up for FDA and the pharmaceutical industry on Capitol Hill.

Heparin safety, the overseas inspections process, DTC advertising, FDA's budget and the integrity of the agency's scientific mission have all been the subject of one or more hearings so far this year.

Indeed, one influential member of Congress alone—Energy & Commerce Oversight & Investigations subcommittee chairman Bart Stupak—has already held four hearings related to pharmaceutical regulation. That doesn’t count his hearing today on DTC advertising and a crowded schedule in 2007, which included a two-part series on drug safety and a four-part series on food safety.

Center for New Drug Evaluation & Research director Janet Woodcock has shouldered more than her fair share of that hearing burden, testifying several times already this year, most recently on the heparin crisis and drug safety in general. She acknowledges the stress of the schedule she’s been keeping on Capitol Hill, but hopes that her testimony has helped put some issues to rest.

“We’ve had a good show for ourselves, at least at CDER,” she says. “We can get criticized, but I think we have answered the criticism, and that’s what we need to keep pressing on.”

One positive outcome may be more money for FDA: Sen. Ted Kennedy (D-Mass.) supports increasing FDA's fiscal 2009 appropriations by $375 million over FY 2008, with larger increases for the next five years. Commissioner Andrew von Eschenbach may have dampened enthusiasm for that big of an increase, however, by telling the Senate Appropriations Committee April 15 that FDA could absorb an additional $100 million in funding in FY 2009.

But the attention isn't all upside: We’ve said it before, but when FDA officials are hauled up to Capitol Hill and bashed over the head for doing a poor job, that doesn’t reflect too kindly on the industries it regulates. Woodcock expressed hope that the attention will start to shift to other issues. “They will continue to have oversight hearings,” she said, but “Congress will become more interested in the electoral process very soon.”

Well, not quite yet. FDA isn’t appearing at Rep. Stupak’s hearing on DTC advertising—executives from Pfizer, Merck/Schering Plough and Ortho Biotech are testifying today. But that doesn't mean they won't be next. We hate to say it, but this is exactly the kind of attention that we (ahem) predicted would happen following the Vytorin/Zetia kerfluffle. Given Rep. Stupak’s preference to hold multiple hearings on a single topic, you can bet it won’t be the last word.

White House Tries to Jump-Start Follow-On Biologics

The Bush Administration seems to think it’s time for FDA and Congress to get back to work on developing a follow-on biologics approval pathway.

The president’s $2.4 billion fiscal year 2009 budget request for FDA lays out an agenda for an abbreviated approval process on follow-on, or “generic,” biologics. “The budget proposes a new authority for FDA to approve follow-on protein products through a new regulatory pathway that protects patient safety, promotes innovation, and includes a financing structure to cover the costs of this activity through user fees,” the request says.

During a conference call, FDA deputy commissioner for operations Jim Dyer said the agency would work with Congress to submit legislation authorizing an abbreviated pathway for follow-on biologics. That’s not really news; the agency has been in discussions with Capitol Hill and industry stakeholders for some time, and has testified in congressional hearings that it has the scientific expertise to support an approval process.

Legislation authorizing a follow-on biologics pathway came close to being attached to the drug safety/user fee bill last year, but was pulled at the 11th hour. For more coverage on the bipartisan negotiations—and what the final deal looked like—click here and here. Subscribers to The RPM Report can read the content for free, or you can sign up for a 30-day free trial.

Practically speaking, the mention of follow-on biologics in the budget request won’t result in much. Finalizing something as controversial as an abbreviated approval process for follow-on biologics during an election year is more than a little optimistic; any real work probably won’t get underway until there is a new president in the White House in 2009.

But the budget request does set the president’s agenda for FDA for the next fiscal year, and lays out what the White House hopes to see the agency accomplish. At the very least, the mention of follow-on biologic user fees will trigger a score from the Congressional Budget Office, which, should it demonstrate savings to the health care system, would be handy during the next round of negotiations.

The request also includes a call to revive user fees for pre-reviews of direct-to-consumer advertising television commercials. A program was enacted as part of the FDA Amendments Act, but Congress killed it off by refusing to fund it in the omnibus appropriations bill. (For more analysis of that story, click here.)

So the Administration, at least, hasn’t given up on that program. Of course, we already knew FDA and industry were eager to make it work—it is Congress that has been of two minds on the DTC program—enacting it in September and killing it in December.

So don’t get too excited about follow-on biologics or DTC user fees. The President’s budget keeps hope alive for action on each this year. But it doesn’t change the basic truth that both issues depend primarily on the priorities of a Democratic Congress in an election year—not the final budget from the outgoing Administration.

Vytorin: Two Sources of Angst for DTC

Rep. John Dingell is one source of cholesterol nightmares for Big Pharma advertisers

Schering-Plough and Merck are halting their direct-to-consumer television ads for Vytorin, surely a sound decision given what appears to be a continuing free fall in use of the combination cholesterol therapy after the disclosure of the ENHANCE study results.

Advertisers are worried about the impact on regulation of DTC in general. An excellent piece in Advertising Age spells out some of the concerns.

But just as the ads themselves highlight the "two sources of cholesterol," we think there are really two sources of concern about DTC raised by Vytorin.

The first is regulatory. Attacks on DTC are not going away, so advertisers are right to worry that any ammunition used against one ad can threaten tougher regulation for all. In this case, the Energy & Commerce Committee is already asking the sponsors and FDA to explain why the ads continued running long after the ENHANCE trial was complete.

But the second is more fundamental: the impact that the DTC advertisements themselves had in turning the failed ENHANCE trial into a commercial disaster for the sponsors. You can debate the medical significance of the ENHANCE findings all you want, but you can't debate this: the very success of the DTC campaign in establishing Vytorin as a consumer brand helped make the failed trial much bigger news than it might have been.

Congress doesn't open investigations of drugs no one has heard of. And national newscasts don't cover equivocal study results for drugs no one knows either.

DTC advertising is expensive and controversial. It also can be highly effective at building a brand and driving prescription growth. Any accurate calculation of the risks and benefits to a particular brand, however, has to consider the potential that an advertiser can be a victim of its own success. That surely is one of the lessons of Vytorin.

Bio-Rad Salutes You

In the unlikely event you haven't seen this over at the WSJ Health Blog today, we felt the need to post this here as well. Bio-Rad has raised the bar. How 'bout it, Applied Biosystems? Whatchoo got?



HAT TIP: WSJ Health Blog, where you can read the back story.

The Man Pharma Loves to Hate

It’s the headline lay media outlets love to report: “High-Cost Cholesterol Drug Combo Shows No Benefit Over Lower-Cost Generic Statin.” From a health care reporter’s perspective, nothing is more juicy than a study that shows that a cheap generic drug is more effective than a expensive new medicine. Especially when the study is sponsored by a drug company.

And that story is made even better is when Steve Nissen goes on national television to say things like this: “My advice to physicians is to not use these drugs...for first-line indications anymore. These should really be relegated to drugs of last resort until we have some evidence that they produce a health outcomes benefit.”

But that’s exactly what happened to Merck and Schering-Plough’s hot new cholesterol combo, Vytorin. The drug, which combines another relatively new drug, ezetimibe (Zetia) with generic simvastatin, was found to have no effect on the accumulation of plaque in the arteries, and may even increase plaque growth.

Yikes. No wonder Schering and Merck waited two years to release those findings. Wall Street certainly showed its displeasure: Schering’s stock price fell 8% yesterday, and Merck’s shares slipped 1.3%. And Merrill Lynch downgraded its rating on Schering’s stock, from “buy” to “neutral.”

But Merck and Schering aren’t just in hot water with investors. The companies released the data after Bart Stupak (D-Mich.), chairman of the House Energy & Commerce Committee, opened an investigation into the delay. Now Stupak is sure to haul Merck and Schering executives up to Capitol Hill to testify at what surely will be a very public, very messy hearing.

“In light of today’s results, which were released nearly two years after the Enhance trial ended, it is easy to conclude that Merck and Schering-Plough intentionally sought to delay the release of this data,” Stupak said in the statement. Stupak, of course, was the man behind the Ketek hearings last spring, when FDA’s David Graham returned to Capitol Hill to revive his role as a drug safety whistleblower. So he’s not exactly friendly with Big Pharma.

That’s all bad enough for Schering and Merck. But Nissen, head of cardiology at the Cleveland Clinic, twisted the knife in a bit deeper, appearing in virtually all major news outlets to blast the efficacy of Vytorin and Zetia. (In fact, we would challenge anyone to find a major news story that didn’t quote Nissen.)

Nissen became the go-to guy on cardiovascular drug safety following his unauthorized meta-analysis of GlaxoSmithKline’s Avandia data. With Vyotrin, he adds the mantle of Dr. Efficacy. Here’s what he told NBC’s Today show: “It was a shocking result for the medical community, and it suggests that this mechanism of cholesterol lowering produced by Vytorin and Zetia is simply ineffective at providing any benefits to patients.”

It was comments like those that led to the anti-Merck and Schering “hysteria” on Wall Street, according to Sanford Bernstein analyst Tim Anderson. “In isolation,” Anderson says, “the results probably would have led to a share price rise for SGP and MRK, but largely due to negative comments from prominent cardiologist Steve Nissen, share prices declined.” (Well, either that or analysts underestimated, and continue to underestimate, how bad these results really are--particularly for Schering-Plough, and especially as those same analysts estimate that "about 70 percent of Schering’s earnings depend on Zetia and Vytorin," according to this morning's New York Times.)

Either way, the reaction confirms our belief that Steve Nissen has become a pretty powerful force, and why our colleague, Ramsey Baghdadi, labeled him as a “serial drug killer.” (For Ramsey’s profile of Nissen in The RPM Report, you can find it here. Those who aren’t yet subscribers can sign up for a free trial to read the story.)

There is an important distinction in Nissen’s role in Avandia and Vytorin: he isn’t taking down Vytorin with his own analysis, but using the visibility gained from Avandia to publicize what he sees as a drug that provides minimal efficacy. But given the sharp drop-off in Avandia prescriptions after Nissen got involved, you can guess where Vytorin and Zetia scripts may be headed—especially once AstraZeneca (Crestor) and Pfizer (Lipitor) start using the data in sales calls.

And finally, for those of you that thought the DTC advertising nightmare was somewhat over, think again. Here’s Nissen on Katie Couric’s “Eye to Eye” last night: “We see no evidence of benefit from this very heavily advertised, very heavily used medication.” If that's not an open invitation for more attention from Capitol Hill, we don't know what is.

DTC User Fees Shot Down; Advertisers Face More Perilous Future

Let’s hear it for the United States Congress. They aren’t too proud to change their minds—at least, not when it comes to tackling the question of how best to respond to those pesky TV commercials for prescription drugs.

In September, Congress enacted a new user fee program to fund pre-reviews of direct-to-consumer television ads, on the premise that both industry and society would benefit by ensuring that the Food & Drug Administration could offer constructive feedback on ads before they air.

The program, part of the FDA Amendments Act, set some tight timelines for FDA and industry to get the system up and running. Together, they got their acts together, crossed all the Ts and dotted the Is, and got the program up and running. FDA even began doing pre-reviews pursuant to the guidelines.

All for naught. In December, Congress changed its mind. In the omnibus appropriations bill signed the day after Christmas, Congress did not fund the new user fee program, and instead gave the agency $4 million in additional money from the Treasury to cover the cost of pre-reviews.

Since FDAAA sets a hard stop to the user fee program—FDA must collect the first round of fees before the end of January—there is now essentially no chance that the Pay TV program (as we liked to call it) will happen.

You have to feel bad for the industry and FDA negotiators who had to herd all the cats to hammer out the new user fee agreement.

Still, on paper at least, this turn of events is great news for advertisers. Rather than paying a fee of over $80,000 per commercial to get FDA’s feedback, they can get it for free. And, in theory at least, FDA can hire just as many new reviewers, but at the taxpayer’s cost—not industry’s. So the agency should be able to provide timeline and predictable responses as planned under Pay TV.

What’s not to like?

Quite a lot in fact. First, there is the thorny question of what happens next year and beyond. Unlike the user fee program, which was intended to run for five years and would have built a reserve fund to ensure stable funding for the ad review group, there is no guarantee that Congress will continue to provide additional funding to support the pre-review program.

That in turn may make it hard for FDA to follow through on its hiring plans. The agency doesn’t want to hire new reviewers this year only to have to lay them off in September when the current fiscal year ends. And even if FDA decides to take that chance, will they agency be able to recruit enough people willing to take a job that could turn out to be short term?

The agency has not decided yet how it will proceed, but promises it will explain its plans soon. (Our guess: FDA will wait until the FDAAA deadline to collect the fees—January 28—and then make the announcement as part of a formal withdrawal of the notices creating the new fees.)

Bear in mind that while pre-reviews are technically voluntary, we think advertisers would be very wise to use that process rather than risk facing the new enforcement actions Congress gave FDA under FDAAA.

Consider the dilemma advertisers will be in if FDA cannot or simply does not provide timely responses. Run an ad and risk a hefty fine? Or wait for an answer—and in effect surrender the right to advertiser that industry fought so hard to protect during the FDAAA debate.

The collapse of the user fee program doesn’t change two important facts for advertisers. First, FDA now has a much stronger hand in shaping TV ads—both in determining if products are advertised as well as what ads look like. (Subscribers to The RPM Report can read more here. Not a subscriber? Sign up for a free trial.)

More importantly, no matter what FDA does in 2008, you can bet that this issue is coming back in 2009. President Obama (didn’t I read yesterday that he had won?) or whomever takes over the White House will select a new FDA commissioner and you can bet DTC will remain a hot button issue.

The Energy & Commerce Committee offered a timely reminder of that fact by opening an investigation into Pfizer’s Lipitor commercials. Those commercials have been held up as examples of the new, more responsible approach industry is taking to DTC. (You have to ask yourself: has the committee seen Pfizer’s new “Viva Viagra” ad?)

DTC User Fees Clear First Hurdle; New Era for Advertisers Ready to Begin

An update on an item we reported last week: the status of the new direct-to-consumer advertising user fee program created as part of the huge Food & Drug Administration Amendments Act enacted in September.

As of November 26, FDA had received commitments from advertisers to submit at least 130 television ads for prescription drugs for pre-review by the agency.

That is well above the 68 commitments the agency needed to get by November 26 in order to launch the program. It is also way more than the 47 commitments the agency had received when Division of Drug Marketing Advertising & Communications Director Tom Abrams provided an update during a Food & Drug Law Institute conference 10 days earlier.

The program was designed with the assumption that there would be about 150 pre-reviews per year. That looks like a pretty sound estimate. FDA may be a little short of that number in advance commitments, but sponsors can decide later in the year to submit ads (albeit with a higher fee as a penalty).

“The next steps are to tally the number of ads and establish the fee per ad,” FDA says. The agency plans to “issue a Federal Register Notice stating the fee and will also invoice the participating companies.” The law requires FDA to have the money in hand by January 26, so there may still be some nervous moments early in 2008 while the agency waits for the checks to come in.

FDA is authorized to collect $6.25 million in fees to fund reviews in 2008, plus another $6.25 million to establish a reserve fund for future years. So if the agency ends up with exactly 130 commitments, the fee for a review will be just under $100,000.

That may sound like a lot to pay for the privilege of having a regulator criticize your ad before it airs.

But it is a pretty small price to pay compared to the alternatives. FDAAA didn't just authorize the new user fee program; it also gave FDA new authorities to punish advertisers that the agency thinks cross the line. Ads pre-reviewed by FDA are safe, as long as the sponsor made all the changes suggested by the agency. The new fines for violative ads start at $250,000 for a first offense, and increase to $500,000 for repeat violations. That’s not a ton of money, but then you have to factor in the cost of being made an example of by the agency.

More importanly, the pre-review program is probably the last chance for industry to fend off more draconian measures to restrict or even ban DTC ads. An outright ban is unlikely to survive Constitutional review by the courts, but that doesn’t mean Congress won’t find other ways to make advertisers miserable.

Now the question is: what exactly will FDA do with its pre-reviews? The agency has always been willing to make comments on ads prior to broadcast, but it has never before had enforcement tools to punish companies that decline to take its advice. We think that change in the balance of power will make a significant difference. You could read more of our thoughts on that in “The New Era of DTC,” from The RPM Report in October.

DTC User Fees: Will This Program Fly?

A new program to allow prescription drug advertisers to pay for a pre-review of TV spot by the Food & Drug Administration is struggling to get off the ground.

With about a week to go before the first critical deadline to create DTC user fees, FDA has gotten commitments from industry to submit 47 ads. That is about 20 short of the absolute minimum necessary to get the new review system up and running—and way short of the 150 ads used as the benchmark in creating the plan.

The new user fees were created by the FDA Amendments Act signed into law September 27. The program allows advertisers to buy a pre-review from the agency; sponsors are free to advertise without paying the fee, but if they want the agency’s feedback before the ad airs, then they have to participate.

The logistics of the program are a bit convoluted. Because the fee is voluntary, the agency first needs a commitment from sponsors to participate; then it calculates the fees and sends out invoices. Sponsors are supposed pay up front; they can change their minds later and pay a penalty to participate.

But if everyone waits, the entire program will shut down. The law stipulates that FDA must collect at least $11.25 million to get the program up and running by January 25. Since there is a cap set on the fee, that means FDA must get commitments from industry for 68 ads in order for the program to take off.

Time is tight. The program was designed with the hopes that everything would be in place ahead of the start of the fiscal year on October 1. That obviously went out the window when FDAAA--which includes groundbreaking drug safety provisions--took most of the summer to complete.

In October, FDA published a notice seeking commitments from sponsors by November 26. During a Food & Drug Law Institute meeting on FDAAA implementation November 16, Division of Drug Marketing Advertising & Communications director Tom Abrams provided an update.

First the good news: FDA is already doing the ad reviews and meeting the goal of responding within 45 days. Abrams says FDA has already gotten 12 ads under the program, and has provided feedback on 4. The agency is comfortable it will answer the next eight within 45 days as well.

But there is reason for concern. The agency has commitments for 47 ads so far, Abrams said. The division director is confident that sponsors are interested in making it happen; he said he understands that the challenge is getting sign off within corporations to make the commitment to participate.

But, he stressed, time is running out. FDA needs answers by November 26 so it can calculate the fee and collect the money.

WilmerHale attorney Scott Lassman, who helped negotiate the new user fee program on behalf of the Pharmaceutical Research & Manufacturers of America, underscored that concern. The new user fee “is in some jeopardy,” he told FDLI.

Assuming companies are able to turn around their commitment notices in time, there will still be some nervous weeks ahead, Lassman pointed out. That is because the deadline for FDA to collect the money is firm: January 25. It is not good enough for the agency to have commitments or even to have invoices out. The law says it must “receive” a total of $11.25 million by then -- or shut down the program.

Oh, and one other thing. Even if FDA does collect the money for the pre-reviews, it can’t actually spend it unless or until Congress passes an appropriations bill for the agency for 2008. FDA is currently operating under a continuing resolution—an issue that hangs over every aspect of implementing FDAAA.

There is a silver lining. As Lassman points out, lower than expected participation should mean faster reviews. Assuming FDA collects enough money to meet the January trigger point--and assuming Congress finishes an appropriation bill in some reasonable timeframe--FDA will be able to hire 27 new staffers just for TV ad reviews. The goals set in the program were based on having 150 ads to review; if the agency only has to review half that many, it should be able to do virtually all of them within 45 days.

The stakes are high, Lassman says. “This is industry’s opportunity to show a voluntary program works,” he told FDLI, noting that there was a big push in Congress for a blanket moratorium on ads for new drugs. Still, he acknowledged, “there are legitimate reasons to deliberate.”

The betting here is that industry will come forward and make it work. Why? Because the “voluntary” user fee program sure looks a lot better than the alternative. As we discussed in The RPM Report last month, the new law also gives FDA the authority to require pre-review of DTC ads whenever it chooses. And, more importantly, it gives FDA the power to impose fines on ads it deems violative.

Anyone who obtains a pre-review from FDA (and makes all the changes requested by the agency) is protected from fines. FDA can still change its mind about an ad, but it must give the sponsor a chance to change the ads before it can levy fines. So the pre-review is really a form of insurance, and one that looks relatively cheap.

So if you plan to run TV ads in 2008, it probably makes sense to get that notice in to FDA before heading out for the Thanksgiving holiday. It may seem odd to be thankful for the chance to pay more money to FDA, but given the alternatives that is probably the right spirit.

Now, who gets the wishbone?