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.

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?

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?)

When DDMAC Attacks

Insomnia drug Rozerem's Your Dreams Miss You advertising campaign may have crossed the line into Nightmare for its marketer, Takeda. (if we can find a copy of the problematic spot, we'll post it here. meanwhile, enjoy Rozerem's pitch in happier times.)

Abe & the beaver, in better days

Admired for their off-beat and clever take on the results of insomnia (and questioned for being too convoluted for the average consumer), the ads, say the FDA, may have gone too far this time.

The agency's division of drug marketing, advertising, and communications (DDMAC) slapped the drugmaker with a warning letter for one of its ten-second reminder ads. For such a short spot, the ad broke a ton of rules. Some of DDMAC's more serious allegations point out that while Rozerem is not indicated for use in children, some of the language in the ad is misleading:

The combination of these statements ("Back to School") and images of school-aged children and school-related objects suggest that Rozerem is indicated for and can be safely used in the pediatric population. The presentation in the TV ad is especially concerning given that the PI for Rozerem includes the following Precaution regarding pediatric use: "Safety and effectiveness of ROZEREM in pediatric pateints have not been established. Further study is needed prior to determining that this product may be used safely in pre-pubescent and pubescent patients." (FDA's emphasis)

That study is warranted because of Rozerem's known affect on reproductive hormones in adults--decreased testosterone levels and increased prolactin levels. Making matters worse, Takeda failed to submit the ad to FDA "at the time of initial dissemination" as required by current regulations.

Yikes, Honest Abe would not be happy. Takeda, go sit in the corner. You're in a time-out.

Incidentally, it makes one wonder who's next ... perhaps the FDA will crack down on Osama bin Laden's endorsement of the erectile dysfunction drug Levitra?