Reputation Counts

Merck has fallen a long way from the days when its CEOs adorned the front cover of Time magazine as respected business leaders (George Merck in the 1950’s) and icons of cutting edge scientific research like the (Roy Vagelos in the 1980s and 1990s).

The image of Merck as the “moral corporation,” the respected leader in innovative pharmaceuticals and research, has suffered blow after blow in the past four years. The most recent hit is a non-admission settlement with the Justice Department and state authorities of charges that the company abused the Medicaid best price rebates and marketing practices. "Non-admission" meaning, "We'll pay the fines, agree to give the government extensive future rights to oversee pricing documents and marketing practices--but we will not admit wrong-doing."

The accumulating financial costs of the bad news events keeps rising: the loss of the $2.5 billion Vioxx franchise; a $4.85 billion agreement to settle liability claims from that product; an 8% drop in total prescriptions in the Vytorin/Zetia group due to the failed ENHANCE trial; and now $670 million in payments to the feds and states to settle the Medicaid case.

But the real cost may be in the future, when Merck takes this new public image with it into efforts to get approval for drugs like the weight loss product, taranabant.

Merck has made some smart hires along the way to prepare for a careful review of the cannabinoid compound including a former senior officials from the FDA review group that will look at taranabant, Robert Meyer, (see here) and the former top FDA drug safety manager, Peter Honig. Their experience should help inform Merck’s handling of the application for the obesity drug and provide solid, knowledgeable advice on ways to assure FDA that the company knows how to address the psychiatric side effects that derailed Sanofi-Aventis’ Zimulti (rimonabant) application.

One of the likely prerequisites for getting an anti-obesity product through FDA, however, is for the sponsor to convince the agency that it will control use of the product carefully and find a patient population for whom the benefits clearly outweigh the risks.

Here is where Merck’s new reputation of pushing in every way it can to extend the market for its products will work against it.

When Merck commanded a high-road image, the company treated its reputation as a corporate asset, a strength that it could use for ambitious but trusted efforts to open new drug categories. The company may have given up some of that strength.

Merck used to have PR people assigned to watch and protect its long-term reputation, paying attention to more than the short-term news cycle and the liability wars. One of those execs, John Doorley, currently the director of NYU’s masters program in public relations, literally wrote the book on “Reputation Management”.

Maybe Merck needs to get a new copy of the book and pay some more attention to rebuilding the trust of the public and regulators before heading into promising but perilous new drug categories.

Read More

The Wacky World of Generics: Fosamax Edition

Today, Merck bids a fond farewell to its Fosamax franchise, as the first generic versions enter the market.

Three generic firms are entering the market: Barr and Teva with approved ANDAs, and Watson with an "authorized" generic supplied by Merck. Next up will be generic versions of the Fosamax D formulation (expected in April) and then numerous additional generics in August when the 180-day generic exclusivity period awarded to Barr and Teva expires.

Authorized generic launches are hardly surprising anymore, as brand firms are committed to maximizing the value of their brands through the patent expiry period. What is surprising is the unusual lengths Merck went to to give Fosamax a send-off in style.

The company ran a promotional campaign in the final months before patent expiration highlighting the upcoming Fosamax generic launches, and even created a website called GoingGeneric.com to promote Fosamax. Merck drove traffic to the site via links on its main Fosamax website as well as through a "multi-channel physician campaign" that included direct mail and journal ads.

We would love to show you the site, which featured a neat animated video of a Fosamax patient on the beach, but Merck has taken it down. The site "served its purpose," a spokesman says. Here is Google's cached version of the page, which has no graphics but at least shows the basic messages Merck was pushing.

The overall theme: Fosamax allows patients to "Save Now and Save Later." In other words, starting new patients on Fosamax rather than a competitor like Boniva or Actonel meant lower copays right away (since most managed care plans had Fosamax on tier 2) and then even lower copays now that generics are available.

In other words, Merck did everything in its power to build a bigger market for the generics that launched today.

What's going on here? Does anyone else remember the good old days when Big Pharma companies would simply shift resources away from brands in their final quarters of exclusivity, jack up the price, and concentrate on new products?

Well, those days are obviously over. "Maximizing the value of the brand" (or, perhaps, milking every drop from a cash cow) is critical business for big pharma at a time when new product launches have slowed to a trickle and cost cutting is the order of the day. At a time when hitting profit targets is a quarter to quarter war of attrition, every penny counts.

That is why Merck not only ran the campaign, but also highlighted it to investors during its December 4 analysts day. "We are prepared for a number of different potential scenarios to insure that we maximize the value of the Fosamax franchise," CFO Peter Kellogg said, and then discussed GoingGeneric.com as an example.

Merck says it expects Fosamax revenues in the range of $1.1 billion to $1.4 billion worldwide in 2008 (down from $3 billion in 2007). That's a big drop no matter what, but the difference between the high and low ends of the range is $300 million. You can bet Merck would love to have that in revenues rather than make it up in job cuts or other efficiency initiatives.

So, if the going generic campaign helped drive higher brand sales in the first six weeks of the year (and then higher sales of the authorized generic during the spring and summer) it would be a big deal for Merck.

Did it work? Its hard to say. Fosamax revenues increased 1% in the fourth quarter to $522 million. That is not exactly spectacular growth, but it reversed a downward trend in sales throughout the year, and helped Merck hit its goal of $3 billion in global revenue for the brand in 2007.

During Merck's fourth quarter call in January, Kellogg credited Fosamax's strong showing to its favorable formulary position in anticipation of generic entry, but did not specifically comment on whether the Going Generic campaign made a difference. And a Merck spokesman declined to provide any additional details about the performance of the campaign, saying the company didn't want to share any lessons learned with the competition.

Whether or not the campaign itself worked, the idea is here to stay. In today's world, Big Pharma has not choice but to drive sales growth of all its brands through every means possible--even if it means building up the market for its generic competitors.

That may be a sign of desperation for Merck, but it is a nice treat for Barr and Teva who unequivocally benefit from anything Merck did to increase the size of the Fosamax market over the past few months.

Our only question: when will Teva and Barr be launching GoneGeneric.com?

Read More

Deals of the Week: Deal--or No Deal

The debate over Vytorin's medical benefits and, by extension, the utility of all cholesterol meds, continues to rage. Meantime, the Zyprexa marketing scandal reared its head: new this week, the NY Times reports Lilly is in talks with federal prosecutors to settle investigations into its marketing of the antipsychotic. If an agreement is reached, it could cost the pharma $1 billion, the largest fine ever paid by a drugmaker for breaking federal laws governing a medicine's promotion.

And, it was earnings week, with fourth quarter reports from Wyeth (up, but flat forecast for '08 due to generic Protonix), AZ (down), BMS (down, and WSJ's Health Blog highlights concerns that this big pharma may be affected by the sub-prime mess), Novo Nordisk (down, but did beat analysts' expectations sending the stock up), and Merck (down, thanks to Vioxx settlements) among others.

All in all, a crazy week, but not necessarily on the deal-making front. That's prompted this IN VIVO blogger to ponder the deals that happened--and those that did not. Without further ado, the Deal or No Deal edition.

First, a look at the actual deals that got done...

Inverness/Matria: On Monday Inverness announced its third major acquisition in the health management space, buying Georgia-based Matria for $900 million and the assumption of $280 million in debt. Definitely the big money deal of the week, though Wall Street reacted negatively to the news. Inverness continues to build through acquisition: the Matria deal is its twelfth in the past 12 months. (For more on Inverness's acquisition strategy, click here.) The company's recent emphasis on health management suggests another trend we've been following: the expansion of the diagnostic business model to include services not exclusively related to in vitro tests or reagents. Such business activity has muddied the waters stretching the definition of what it means to be a diagnostic company.

Sepracor/Nycomed: A few weeks ago when Nycomed got FDA approval for its inhaled corticosteroid ciclesonide we figured Sanofi-aventis, the original partner of Altana (bought by Nycomed in '06), still had US rights to the drug--we hadn't heard otherwise, after all. So we were a little surprised on Monday when Sepracor picked up rights to the drug (Alvesco) for $150 million upfront plus various development and sales milestones. Nycomed will also receive payments for manufacturing and royalties on sales. Alvesco's route to the US market has been chock-full of speed bumps. Way back in 2002 Altana suggested the drug might be approved in 2003, but an NDA wasn't filed until December 2003. Altana and Aventis received an approvable letter in October 2004 and the drug was launched in 2005 in Europe.

Iroko Pharmaceuticals/ Merck: Specialty pharma Iroko inked a deal with Merck for non-US commercial rights to Aggrastat, a drug used alongside heparin in patients with unstable angina to prevent cardiac ischemic events. Financial terms of the deal were not disclosed. This is the third product Merck has out-licensed to Iroko and the second in the beleaguered cardiovascular space. Last spring the company acquired rights to Indocin, for rheumatoid arthritis, and Aldomet, a hypertension treatment, from the big pharma. As we reported here, the independent futures of many spec pharmas are in question, as product-poor pharmas gobble them up in hopes of fattening their pipelines. Still, primary care remains a popular space for many, especially as big pharma eschews risky products in the cardiovascular and metabolic disease space.

(Clearly someone forgot the briefcase models.)

BiogenIdec/Genmab: Perhaps we should say "No deal, yet." This week BiogenIdec was once again in the news thanks to manueuvers by Carl Icahn to install three supporters onto the company's board. Also swirling in the ether, rumors that BiogenIdec intends to buy Genmab. Certainly, such a deal would scupper any attempts by Icahn to sell the company to another entity. Adding Genmab's pipeline would go a long way to securing an independent future for the Cambridge, MA-based biotech. But such a deal won't come cheap. In part, because it seems likely that GSK might up the ante. The British pharma, after all, has three partnerships with Genmab, including a very rich co-development, co-promotion deal for the biotech's HuMax-CD20, an antibody to treat cancer and rheumatoid arthritis. Until now, GSK's had no real reason to bring Genmab in-house--it's already got rights to the antibody cow's milk, after all. But it may not be willing to stomach the risk associated with a change in Genmab ownership, deciding its worth the hefty price tag to nail down its rights to its partnered products.

Lilly/Gastrotech: Deal or No Deal? Here's an odd one for you. On Jan 28, Denmark’s Gastrotech Pharma announced it was in-licensing Lilly’s GLP-1 analog GTP 010 for IBS and functional dyspepsia. That’s a deal, not a non-deal, surely? Well, depends on how you look at it. Simply turn it over and you get….a non-opt-in by Lilly.

Lilly and Gastrotech had been collaborating on GTP 010 since 2004, when Gastrotech took over Phase II trials of this Lilly compound in IBS and dyspepsia (in part thanks to the biotech’s ownership of some use patents for GLP-1 analogs in IBS, according to chairman Hans Schambye, though no, that wasn’t mentioned in the release).

That—four years ago--was arguably the real licensing deal. And that was also when Lilly received an option to later take over development and commercialization of the compound in return for milestones and royalties.

This week's news is that Lilly didn’t take that option, which means Gastrotech gets to keep the compound, instead, paying Lilly royalties. “Sure,” Schambye acknowledged to IN VIVO Blog, “you could look at it both ways. Either party could have licensed the drug.”

See? Hmm, exactly. Now ok, we know that small biotechs need all the positive spin they can get, but we're getting pretty close to "Press Release of the Week" territory here. Perhaps Gastrotech will do something big with 010, who knows (Lilly did take an equity stake). But please, a bit of clarity and objectivity wouldn’t go amiss.

Read More

Deals of the Week: Beyond Vytoringate

The sky is falling! The sky is falling! It sure seems that way this January Friday morning. Global markets slid early in the week thanks to a certain R-word and its association with the US economy. Meanwhile, in pharma land the brouhaha over Vytorin data--or lack thereof--has officially morphed into a scandal, with the addition of the "gate" suffix. (Take our poll!)

As of Thursday, both houses of Congress had initiated investigations, pressing Merck and Schering-Plough for information on the timing of executive stock sales in the wake of the delayed release of results from the so-called ENHANCE trial. Adding to the bad news, comes this New York Times report, which draws the American Heart Association--remember, the group came to the defense of Vytorin just last week--into the scandal thanks to financial ties to both companies.

In the wake of such scrutiny, it's not surprising that Vytorin prescriptions have fallen. Any doubt that these two pharmas have a serious image problem should be erased by this spoof from YouTube, where the omniscient narrator voices, "Nobody knows if Vytorin is safe or effective, but with enough scientific fraud, we can sure make it look like it is."

2008 is off to a great start. Thank goodness for Deals of the Week, where we promise not to mention Vytorin, Merck, or Schering Plough again--at least in this edition.



Teva/Cogenesys: On Tuesday, the Israeli generic drugs company announced it's acquisition of Cogenesys, the albumin fusion technology play spun out of Human Genome Sciences in 2006, for $400 million. Yet again, proof of a trend we've detailed several times: pharmaceutical firms continue to bulk up their large molecule capabilities. But for generics giant Teva, this deal is as much about deepening its stake in the ill-defined, yet surely valuable, follow-on biologics arena as is it about biologics capabilities per se. And that got us thinking. How much different is this deal, really, than Glaxo's take-out of Domantis, BMS's buy-out of Adnexus, or Wyeth's acquisition of Haptogen? Pharma's made a tremendous amount of money on next-generation (or me-too) small molecules. Stands to reason that as these firms jump into biologics, this might be just the space to play in--after all, new technologies allow the pharmas the opportunity to create IP-protected versions of existing large molecules that have largely been derisked. (Note: It's probably a good thing for Cogenesys that Teva inked the deal Tuesday not Wednesday. On Wednesday came news that HGS's own albumin-fusion protein, Albuferon for the treatment of Hepatitis C, may have adverse lung-related side-effects when dosed at the 1200 microgram level. HGS says it will shift patients in the Phase III trial to a 900 microgram dose biweekly and still expects to have late-stage data on the drug by spring 2009, with a marketing application to follow later that year.)

Roche/Ventana: Requited love--isn't it romantic? On Tuesday,came the news that after attempting to pledge its troth five times--and upping its share price to $89.50--Roche finally won Ventana's hand. We advised Ventana to take the outsized $75-a-share price late last summer, as $3 billion for a company with no near-term products seemed an outrageous return. Looks like we were wrong. That extra few months of wrangling won Ventana shareholders an extra $400 million in value, with the purchase price coming very close to the $90-per-share target Ventana CEO Gleeson had been gunning for all along. But even this happy news hasn't quelled the on-going rumor-mill. Forbes is reporting that although Ventana’s board has approved the deal it was over the objections of Chairman Jack Schuler and Vice Chairman John Patience. Neither have agreed to sell their shares to Roche. That’s 12% against the deal. Larry Feinberg, manager of the $1 billion Oracle Partners hedge fund owns another 8% of Ventana’s stock. He started buying in 1999 and tells Forbes: “My strategy has been to go along with those guys.”

Estee Lauder/Allergan: Last week the self-help guide "How Not to Look Old” made its debut on the New York Times best-seller list at No. 8 in the advice and how-to category, proof that the quest for eternal youth remains a constant in our society. This week comes news that Estee Lauder Cos' Clinique Laboratories is teaming up with Allergan to develop and market a new up-scale skin care line that will only be available from physicians. The new line will be priced at a premium compared to both Clinique's retail products and Allergan's physican dispensed offerings, which include Prevage MD and Forte. "The big idea here was: How do we become a leader in skin care?" says Allergan's CEO David Pyott. Allergan, is of course, the company that brought the world Botox, and has been a leader in showing the world how lucrative it can be to blend cosmetics with aesthetic medicine.

Forest/Novexel: Forest Laboratories plans to shell out $109.5 million in up-front fees to license North American rights to Novexel's preclinical intravenous beta-lactamase inhibitor, NXL104, which is being developed in combination with Forest's ceftaroline. (For those who don't remember, Forest acquired that product as a result of its 2006 acquisition of Cerexa.) If development work bears fruit--the combination is scheduled to enter the clinic in 2009--Forest will owe an additional $109.5 million. In addition, Forest also won first negotiation rights on another combination antibiotic--NXL104 plus ceftazidime, another cephalosporin with a slightly different activity spectrum compared to ceftaroline. This is the seventh major in-licensing deal for Forest in the last two years. While other pharmas have looked to biologics and other novel technologies to rejuvenate their pipelines, Forest is proving it has the know-how to license and succeed with primary care products, from anti-infectives to hypertension medicines such as Daiichi Sankyo's Azor to irritable bowel syndrom drugs such as Microbia's linaclotide. In other words, this spec pharma is proving it can succeed in big pharma's sandbox. For more on Forest's efforts in the primary care space check out this article from the December issue of The RPM Report.

Read More

The Best Defense Is a Good Offense, Or Something Like That

Merck and Schering-Plough put out a release a few minutes ago responding to critics of ENHANCE and the trial results' fallout:

WHITEHOUSE STATION, N.J. & KENILWORTH, N.J.--(BUSINESS WIRE)--Merck and Schering-Plough said today that they strongly object to mischaracterizations about the ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia) trial. “While the ENHANCE trial was time consuming and took longer than originally anticipated to complete, our companies acted with integrity and good faith in connection with the trial. We took numerous actions to assure the quality of the reading of the ultrasound images,” said Thomas Koestler, Ph.D., president, Schering-Plough Research Institute.

And from there it gets more defiant. So, dear readers, what do you think? Read the whole release. Is this an effective defense for Merck and Schering-Plough? Please take our poll:

Read More

Vytorin: In this Case, Best to Ignore History

Are the experts right? Or is this another example of the wisdom of crowds?

Analysts are pooh-pooh’ing the Vytorin/Zetia affair. Tim Anderson of Sanford Bernstein wrote that ENHANCE will “likely only have a muted impact on Vytorin prescription trends given the limitations of the study, but some prescriber business may be lost on the margin contingent on much negative coverage ENHANCE continues to receive.” Catherine Arnold at Credit Suisse in a note on Friday talked about investors reactions as “excessive and disengaged from the fundamentals.”

So far, the market isn't listening. Merck’s stock was down last week 10%; Schering-Plough’s 23%.

Docs aren’t paying attention to the analysts either. Daily data from ImpactRx show steep declines in new scrips. Notes ImpactRx analyst Bob Caprara: if you look at 2-day averages, Vytorin has lost 75% of its new patient starts and was still trending down last Friday. If you continue to draw that line, Vytorin could easily lose 35% of its 2008 projected sales, he says.

Admittedly, Caprara notes, that’s a big if. Schering and Merck might be able to counter the negative press. Arnold argues that “there are no sound historical comparisons for a drug coming under this much fire for a disappointing efficacy study, especially when the study looked at an unvalidated surrogate endpoint, tested the drug against a strong active comparator and showed equivocal results.”

Maybe. Other drugs have faced a barrage of criticism and recovered – most notably, as Arnold points out, AstraZeneca’s Crestor. But we’d submit the Vytorin situation is no Crestor redux, and Crestor’s antagonist, FDA's internal gadfly David Graham, is no Steve Nissen (we blogged about one of Nissen’s attacks on the drug here). In the first place, Graham could point to no single trial to define his point. Vytorin’s critics now can. And that woefully-late-to-report trial looks to those with a suspicious caste of mind (including the New York Times editorial page and US legislators) like it was suppressed.

Then there’s the lower-is-better argument that the drug industry has used so effectively to boost one statin over the previous while driving sales in the category beyond the wildest dreams of its creators – first Merck, with Zocor over Bristol-Myers’ Pravachol, then Pfizer, with Lipitor over Zocor, then AZ with Crestor over Lipitor; and now Merck and Schering with Vytorin over Lipitor and Crestor. When you think about it, there ain’t all that much data comparing head-to-head outcomes data on the most powerful drugs – Vytorin’s IMPROVE-IT trial vs. Zocor won’t report out till at least 2010; the Crestor vs. Lipitor study not until 2011. And while Arnold is right that the ENHANCE study focused on a surrogate endpoint – atherosclerosis as measured by intima-media thickening – it’s an endpoint a lot closer to a real clinical endpoint than mere cholesterol reduction.

But whether Vytorin sales slump permanently or not, the real message is that primary-care risk is now off the charts, exacerbated by Big Pharma’s addiction to DTC advertising. In fact, we think the risk will bite a virtually permanent discount from the share price of firms whose earnings now or will flow largely from primary care products, particularly those – like Vytorin – which treat asymptomatic diseases.

There are several reasons why. First, with the general lack of head-to-head outcomes data – and understandably little appetite among Big Pharma for financing it pre-approval –payors will increasingly look to switch their insured populations towards generics. And this is particularly easy with asymptomatic conditions like hypercholesterolemia because patients have very little practical reason to care. Their disease doesn’t hurt; the drugs provide a merely theoretical benefit. At least diet and exercise make you look better.

Second, these drugs are the easiest ones to attack. There are no patient cholesterol or hypertension or diabetes lobbies that can compete with breast cancer or AIDS or Alzheimer’s. The makers of the big primary-care drugs are easy targets for politicians – and evidently more frequent targets, too (thanks in part to the backswing of the double-edged DTC sword Big Pharma has been wielding so aggressively). Merck and Schering will be asked to explain themselves to Congress (and no doubt FDA will be obliged to hold an advisory committee as well). That means more headlines and more questions. As we wrote here, it won’t help that the Energy & Commerce Committee, which is investigating Vytorin, is also investigating Pfizer’s Lipitor DTC campaign.

And you add those headlines to the fact that the drugs don’t actually make people feel better – and a compliance problem the drug industry has always struggled with will grow worse.

Let us return to Catherine Arnold’s point: “there are no sound historical comparisons for a drug coming under this much fire for a disappointing efficacy study.” Exactly. History -- the rear-view mirror -- isn’t where we should be looking to understand the meaning of the Vytorin story.

Photo 'Crowd listening to T.R. speak, Chicago' from Library of Congress, via Flickr

Read More

While You Were Losing Your Resolve

Allegedly this is the time of year that most of us begin to let those New Year's resolutions slip. (Already? Weak!) Trip to the gym or grab a beer to watch the conference championship games? We watched football--but then again we were smart enough not to make any resolutions this year. Pack and Charger fans, better luck next year.

Just a couple notes from a cold and quiet Sunday. If you're taking the day off in observance of Martin Luther King Jr. Day, enjoy the long weekend.

• Start saving for a super bowl ad: Merck and Schering-Plough defend Vytorin and Zetia in some full-page ads on Sunday. Will doctors and patients respond? We'll have some data on their early reactions to the Enhance kerfuffle later today.


• Lupus, unmasked: Scientists writing in the New England Journal of Medicine and Nature Genetics describe unearthing genetic variants in at least six distinct regions of the genome related to the autoimmune disease systemic lupus erythematosus. Reuters' roundup is here.

Read More

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.

Read More

Nissen Weighs in on ENHANCE

You know what he's going to say ...



Remind you of this?

Read More

The Stakes Increase on Comparative Effectiveness

When the Congressional Budget Office released its long-awaited report on comparative effectiveness last month, its overall conclusions were pretty much what were expected, based on director Peter Orszag’s public previews.

A comprehensive, national effort on comparative effectiveness will eventually save the US health system money, CBO determined. But for the next 10 years or so, more money will be spent implementing the program than will come out the back end in savings. And, as Orszag stressed in public comments leading up to the release of the report, success will be largely enhanced if the results are tied to financial incentives.

The RPM Report has written extensively about the potential for a national effort on comparative effectiveness—you can read our stories here and here. So is this bad news or good news for the pharmaceutical industry? Well, that largely depends on who you talk to, and, dare we say, what products are in the pipeline.

Merck is one of the more outspoken supporters of comparative effectiveness, dating back at least a year to an editor’s note from CEO Richard Clark (pictured here) in The American Journal of Managed Care. In fact, Clark is so on board that Merck redefined its approach to R&D and marketing based on a “value proposition.” Importantly, he wrote, “it is no longer enough to say that a drug has a new mechanism of action.”

Clark echoed that sentiment with investors during last week’s Morgan Stanley CEO’s Unplugged conference, selling comparative effectiveness (or “health economics,” as he put it) as a way to address FDA’s higher approval standards for new products.

Merck acknowledges its endorsement of comparative effectiveness isn’t winning any popularity contests among its peers. Indeed, other pharma companies have been somewhat less receptive. During a recent Kaiser Permanente Health Policy Forum, Sanofi-Aventis public policy director Jean-Paul Gagnon argued that the lifespan of a comparative effectiveness review is only three to five months. Beyond that, he argued, any findings should be considered suspect, given the changing science. That’s not exactly a ringing endorsement for comparative effectiveness. (In fact, using that philosophy, you might ask whether it’s even worth it.)

But maybe comparative effectiveness is easier for Merck to push as a priority right now, given the flush state of its pipeline. With the failed development of Arcoxia safely behind it, Merck can point to products like the type 2 diabetes drug Januvia (thought to have fewer side effects than existing products) and Gardasil (the first approved HPV vaccine) as “breakthrough” products worthy of winning a comparative effectiveness test.

Merck is smart to be ahead of the curve. The CBO report endorsing comparative effectiveness is an important political step in creating a national effort. But Clark is right: comparative effectiveness will be the wave of the future regardless of whether Congress creates a national agency, for one simple reason: FDA’s approval standards will demand it.

Read More

Deals of the Week: New Year's Resolutions

It's day four of the New Year and you've already broken that resolution to exercise, eat better, or spend more time with the family. Hey, it's okay. Those are tough ones to keep.

So how about an easy one: tune in every Friday for a run-down of the week's most interesting biopharma deals. It's a quick, easy way to stay on top of the industry's events, leaving more time for the kiddos or the gym, or your blackberry.

Once again, we bring you:

(Aren't you glad we aren't on strike?)

Admittedly, deal-making activity has been lighter than usual this past week. We surmise that's because execs are shining their shoes, amassing their business cards, and honing their laser pointer skills in preparation for the biotech's annual coming out party, aka the JPM conference. (The burning questions: 1. Can a company's success be correlated to its executives' neckwear preferences? 2. What color will the famous tote bag be this year?)

Sepracor/Bial: Specialty pharma Sepracor inked a much-needed licensing deal with Bial on Wednesday for the Portunguese drug maker's Phase III anti-epileptic compound BIA 2-093. (Naturally enough for Sepracor, the drug is an enantiomer, (S)-licarbazepine, a metabolite of an analogue of the off-patent anti-convulsant carbamazepine.) Last year the company lost the bidding war for Kos Pharmaceuticals to Abbott Labs and analysts began raising questions about the company's pipeline beyond its insomnia drug Lunesta. (For more, read here.) Under the terms of the agreement, Sepracor will pay Bial a $75 million up-front fee, plus an additional $100 million in development and regulatory milestones for rights to the compound in the US and Canada. In addition, Sepracor will also file the compound's new drug application with the FDA, which should occur late this year or early in 2009. "Strategically, BIA 2-093 further strengthens our existing central nervous system portfolio, which includes Lunesta for the treatment of insomnia, as well as earlier-stage candidates for various central nervous system disorders," said Adrian Adams, President and Chief Executive Officer of Sepracor in a company press release.

Merck/Addex: In terms of "biobucks", the Merck/ Addex agreement was the week's biggest splash. As we wrote yesterday, the two companies announced an exclusive licensing agreement centered around the Swiss biotech's ADX63365, an allosteric modulator currently in preclinical development for schizophrenia and other undisclosed indications. The deal terms are potentially rich: Addex could see up to $680 million in downstream development, regulatory, and sales milestones, but that would require an unlikely alignment of the R&D planets. Guaranteed money was not quite as generous, but the solid upfront of $22 million for a non-clinical compound does suggest Merck is taking the idea of allosteric modulation seriously, and is roughly an order of magnitude greater than the company's previous discovery deals ... so who knows what a deal around its lead Phase IIb candidate might look like (you'll have to wait til next year to find out). For more on Addex and allosteric modulators check out this profile of the company from the January 2006 START-UP.

Sanofi-Aventis/IDM Pharma: Bad news for IDM Pharma this week. On Monday, the company learned that its partner since 2002, Sanofi-Aventis, would no longer help develop its dendritic cancer vaccine, Uvidem, which is currently being tested as a melanoma treatment. No reason was given for the move, but cancer vaccines have had a tough go in recent months, especially after the FDA required one of the field's leading lights, Dendreon, to submit additional efficacy data for the approval of its immunotherapy Provenge. IDM noted in a release that it will continue to evaluate the Uvidem clinical program, which recently completed Phase II trials "with promising results." But already, restructuring plans are in the works, involving "staff reductions in the Company's workforce and a review of the assets and costs associated with products under development." The news comes just weeks after the biotech issued a press release with updated news about its pipeline and a promise to investigate "strategic alternatives."

Sanofi Pasteur/Crucell: On Thursday, Dutch antibody maker Crucell and Sanofi Pasteur, the vaccines division of Sanofi Aventis, announced they were teaming up to develop next-generation rabies biologicals to be used in association with a vaccine for post-exposure treatment against this fatal disease. Under the terms of the agreement, Sanofi will pay Crucell 10 million euros following the deal's execution; Crucell could receive an additional 66.5 million euros in milestones as well as an undisclosed percentage on sales of the final product if the rabies antibodies pan out. To date, Crucell has developed a combination of two rabies mABs that are well tolerated and provide immediate neutralizing activity in Phase I clinical trials. Crucell expects to enter Phase II clinical trials in the first half of this year. If approved, peak sales of the rabies antibody cocktail could exceed $300 million.

Read More

Addex Ups Dealmaking Ante

Addex Pharma today took a step up the dealmaking ladder, partnering its pre-IND positive allosteric modulator ADX63365 and back-up compounds with Merck & Co. for $22 million upfront plus milestones and royalties. Addex can also opt to co-promote resulting products in certain EU countries.

63365 targets the metabotropic glutamate receptor 5 (mGluR5), which Addex says has shown antipsychotic properties improvement of cognitive dysfunction in preclinical studies.

The worldwide exclusive license deal comes on the heels of the two companies' $3 mllion up-front December pact, a discovery deal around positive allosteric modulation of a related receptor, mGluR4, which could lead to products to treat Parkinson's and other diseases. Addex inked an earlier discovery deal in 2005 with Johnson & Johnson around positive allosteric modulators of mGluR2.

Addex's allosteric modulators bind to sites on drug targets that are distinct from the target's active site, where endogenous ligands or conventional drugs bind, offering a variety of potential advantages. Positive allosteric modulators (PAMs) can potentiate the effects of endogenous ligands or conventional drugs, while negative allosteric modulators (NAMs), such as Addex's lead compound ADX10059, can dampen the effects of endogenous ligands (see above).

Enthusiasm for today's deal may be tempered a bit with news that ADX10059 did not reduce acute anticipatory anxiety in a small Phase IIa study in patients with dental anxiety, also announced this morning. Addex has previously reported successful Phase IIa results for 10059 in GERD and migraine, however, and the biotech aims to partner the candidate post-Phase IIb.

Ladder photo from Mayhem & Chaos Photo Blog used under creative commons license

Read More

ENHANCE Interrogation Technique

So what was our colleague Ramsey Baghdadi's "little birdie" talking about when s/he said to expect "something big" to get released this week?

Maybe it was yesterday's encore public throttling of Avandia in the Journal of the American Medical Association. That study concluded that older (age 66+) patients on Avandia had "an increased risk of congestive heart failure, acute myocardial infarction, and mortality when compared with other combination oral hypoglycemic agent treatments."

But we're not so sure--the sequel is rarely as good as the original, and why would anyone be whispering to a journalist about a study that was probably available on an embargoed basis anyway.

Perhaps instead our avian friend was referring to the latest chapter in the ENHANCE saga? Yesterday Schering-Plough's Fred Hassan and Merck's Dick Clark got some mail from the House Committee on Energy and Commerce, and it wasn't a Christmas card.

The letter, from committee chairman John Dingell (right) and subcommittee on oversight and investigations chair Bart Stupak, both Michigan Democrats, questions the companies' delay in releasing data from the ENHANCE study, which concluded in April 2006. ENHANCE was designed to compare the efficacy of Vytorin (ezetimibe [Zetia] plus simvastatin) and simvastatin alone.

Merck and Schering-Plough have five billion reasons to hope Vytorin does a better job of preventing plaque buildup in the arteries than now-generic simvastatin, and a combination of the significant and multiple delays in releasing data from the 720-patient trial, a delay in registering the trial with clinicaltrials.gov, and the apparent manipulation of the trial's primary endpoint drew the Congressional attention.

As the WSJ's Health Blog reports, both companies are still reviewing the letter and have yet to repond. For now, they say the data will be released at next March's American College of Cardiology meeting. Meanwhile, Dingell and Stupak contend the pharmas have some explaining to do.

But who knows, maybe that little birdie has something else up its sleeve.

Read More

Deals of the Week: It's the End of the World as We Know It

Been reading the news this week? Apparently the sky is falling in pharma land. The WSJ reports that pharma's golden age is on the wane thanks to looming patent expirations and a poor track record in product approvals. (Hmm. Where have we heard that before?) BMS is the latest pharma to announce lay-offs--yesterday it announced 10% of its workforce would go. China's drug manufacturing capabilities pose a national security risk according to the Kansas City Star. Poor Carl Icahn: it looks like Henri Temeer and Genzyme will elude his clutches after all. (For more on Genzyme's strategy, make sure to watch for our upcoming IN VIVO feature.) And an FDA advisory panel nixed the use of Genentech's Avastin for breast cancer, sending the company's stock price plunging. (C'est la vie. You can't win 'em all right?)

Yep, it's the end of the world as we know it. And I feel fine. (Thanks to Deals of the Week, of course.) Without further ado:

• Novartis/Morphosys: First up: we tip our hats to Morphosys for their avoidance of pure "biobucks" figures in telling the world what they stand to gain in milestones from their latest HuCAL alliance with Novartis, announced Monday. Revolutionary! Now on to the deal, which for Morphosys is a bit revoluationary itself. Novartis will pay the antibody specialists $600 million over ten years in committed payments (roughly 50/50 technology license fees and research support), with an additional $400 million (non-biobucks) in predicted milestone payments. Morphosys basically consolidates its discovery partnership program into this one deal--as older deals come up for renewal, they'll just expire; for example the biotech's deals with Bayer-Schering and Centocor, scheduled to expire at the end of the year, will do so. Interestingly, Morphosys is maintaining more than a small amount of independence. Novartis remains the biotech's largest shareholder, but hasn't upped its stake beyond the 7% it already held, and does not get a seat on the Morphosys board. Morphosys won't be doing any more discovery deals, but will be able to do product-focused outlicensing deals at its leisure. Novartis gains a fully human antibody discovery engine without breaking the bank.
• Merck/Addex: Not a huge deal, cash wise, but the kind of deal Addex's investors were hoping for. Addex gets $3 million upfront from Merck & Co. plus milestones and undisclosed royalties. The companies are targeting the mGluR4 receptor to develop treatments for Parkinson's disease and other indications. Addex's allosteric modulation platform essentially allows modulation of GPCRs without binding to the receptor's active site, leaving that prime real estate open for the receptor's endogenous ligand.
• Pfizer/Adolor: On Wednesday, Adolor signed a deal with Pfizer worth $30 million up-front and $232.5 million more in milestones for two compounds for pain conditions, ADL5859 and ADL5747. Both compounds belong to the delta opioid receptor agonist class, a class of pain drugs related to morphine and oxycodone, but potentially without their debilitating side-effects. As part of the deal, the two companies will split revenues and expenses in the US 60/ 40 with Pfizer taking the lion's share and Adolor retaining co-promotion rights. This is the third big deal this year for Pfizer in the pain space. This summer the company added to its pipeline, signing a $195 million deal with Hydra Biosciences for its TRPV3 antagonists and a $1 billion-plus deal with Icagen for a sodium channel modulator (For more coverage of the pain space see this 2006 IN VIVO story.) This is some much needed good news for Adolor. The company's stock was decimated earlier this year when the FDA put the brakes on the company's mu-opioid receptor antagonist Entereg because of concerns about its lack of and potential CV side-effects. (For more on this product and other GI-related opioid compounds check out this November IN VIVO feature.)
• Lilly/Aveo: Precision Therapeutics wasn't the only diagnostic company making news this week. (For more on Precision's merger with Oracle Healthcare Acquisition Corp. check out this IN VIVO Blog post.) Cancer biomarker play Aveo Pharmaceuticals announced Tuesday it had struck a deal with Lilly to help the pharma identify patients who respond to one of its cancer drugs under development. Aveo's famous for its in vivo cancer models--essentially mice that have been engineered to develop tissue-specific cancers under controllable conditions. To date, the company also has biomarker discovery deals with Schering Plough, Merck, and OSI Pharmaceuticals. Terms of the deal weren't disclosed but if there anything like the $20 million agreement Aveo inked with OSI earlier this fall, it's unlikely there's big money on the table. Historically, that's been one of the problems with the business models of these molecular diagnostic companies. Although they can sign somewhat lucrative fee-for-service deals with pharmas, these partnerhips never seem to translate into upside related to the actual commericalization of a product.
• Fresenius Medical Care/Renal Solutions: On November 29, the German dialysis product maker announced it was buying Renal Solutions, a venture-backed sorbent cartridge maker for as much as $190 million. Just two years ago, Fresenius bet big, buying Renal Care Group for $3.7 billion. That transaction gave the German company an important foothold in the US market, giving it access to more than 30,000 patients at over 425 dialysis centers. The company also made waves when it agreed to a five-year sole-supplier deal with Amgen in October 2006 for that biotech's Epogen and Aranesp. The reason: many critics saw it as aiding Amgen's strategy to prevent widespread US uptake of a competing product from Roche called Mircera. (For more on Amgen and its anemia franchise click here.)

Read More

While You Were ...

So what were you up to this weekend. Perhaps you were flying to Hamburg for the BIO shindig? Or throwing back a few half-pints at the (outstanding) Woking Beer Festival? Re-reading "The Naked and the Dead," maybe. Whatever your poison (ours was Tryst Brewery's Carronade IPA) we hope you had a good weekend.

• Novo Nordisk tells the Times: Exubera may have gone up in smoke, but inhaled insulin isn't dead yet. We'll be taking an in-depth look at the future of inhaled insulin in the next IN VIVO.


• Medical meeting season rumbles onward; at the American College of Rheumatology, on Saturday, NicOx presented further Phase III data from its '301' study of naproxcinod. Specifically, the company reported positive GI- and blood pressure-related safety and adverse event data for the drug candidate, a nitric oxide-donating form of naproxen that some analysts hail as a blockbuster alternative to the blighted Cox-2s. We've written extensively about naproxcinod here.


• Drug-coated stents are the new eggs. First they're good for you. Then they're bad for you. Now, apparently, good for you again. But manufacturers aren't holding their breath for a massive rebound in sales. The New York Times reports.


• Has Merck been punished adequately in the whole Vioxx debacle? Not everyone thinks so. Pharmagossip rounds up the usual suspects.

Read More

While You Were Watching the Upsets

This weekend we were in Cardiff for the Rugby World Cup quarterfinal between France and New Zealand, which saw France upsetting the favorites. Earlier in the day defending champs England upset heavily-favored Australia, setting up a very surprising all-Europe semifinal next weekend. Suckers for a lost cause, we managed to keep tabs on the Phils into the wee hours, and showed our support on the streets of Cardiff amongst the hordes of Kiwi and French fans (see below--it's a jungle out there).

So what'd we miss?

• The repercussions of the failure of Merck's HIV vaccine are being felt across the entire field, points out the Philadelphia Inquirer.
  
• Roche isn't raising its offer for Ventana, the company said this weekend, but it remains convinced Ventana shareholders will see the light.
  
• And the winner is ... Andrew Witty. GSK's head of Europe appointed CEO-designate, will replace JP Garnier in May 2008.

gotta support the team

Read More

Merck: Embracing Externalization, From the Top Down

Updated Below. One business magazine greeted the tenure of Dick Clark as Merck's new CEO in 2005 with the instruction to "say hello to boring," Roger Longman reminded the audience today at PSA. Investors will be clamoring for more boring if that's what has spurred Merck's shareprice onward and upward over the past two years.

Our Pharmaceutical Strategic Alliance conference kicked off this morning with Roger's Q&A with the Merck CEO, in a discussion that focused on the changes implmented by Clark over the past two years and the challenges faced both by Merck and the industry as a whole.

Clark said many of the things you'd expect a CEO to say. He talked about putting patients first, talked about unmet needs and striving to discover and develop strongly differentiated products. He acknowledged the industry's regulatory challenges and difficult reimbursement environment. And he deflected much of the credit for Merck's recent success to the pharma's employees in general and the interdisciplinary, horizontal and empowered teams that were behind the success of recent launches of Januvia and Gardisil in particular, as well as the timing of his appointment, suggesting his predecessor Ray Gilmartin had put necessary processes in place that have helped the company succeed today, not least hiring Merck's current research head Peter Kim.

And while the executive has spent his entire working life at Merck, he credits his several years at Medco--then Merck's PBM subsidiary--with providing him an external perspective on the company that once felt that the only good science was the science done in its own laboratories.

Externalization, both as an industry meme and in practice at Merck is becoming more important. "Medco allowed me to take an outside-in approach at Merck," Clark says. It's an approach that has more or less been embraced company wide. Only a few years ago, Clark noted, Merck did only a handful of licensing deals per year. "Last year we did something like 53," he said, pointing out acquisitions like the recent NovaCardia deal, and large molecule platform building moves like buying GlycoFi, Abmaxis, and Sirna. Scientists and managers within Merck are no longer rewarded based soley on what they can develop and create in-house, but for what they can bring into the company from the outside as well.

And there is still a ways to go, says Clark. "It’s important to understand that Merck hasn’t declared victory yet, that we’re about 40% of where we want to be and there’s still a lot of work to do." The danger, he says, is to revert to an internal focus.

Commenting on the $1.1 billion acquisition of Sirna in the RNA interference space, Clark emphasized the importance of continuing to augment its platform with the best available technologies. "I don’t think it ever ends, the external focus has to continue. If you raise your hand and write a billion dollar check," you need to make sure you're putting the right tools to work to execute your strategy.

UPDATE: The WSJ's Health Blog dropped by this morning. You can read their take on Clark's talk here.

Read More

While You Weren't Working

For those of you in the US, we hope you had a relaxing three-day weekend. Here are a few items you may have missed while sparing a thought for the Noble and Holy Order of the Knights of Labor and/or enjoying a cocktail. Not everyone took the weekend off ...

• Merck & Co said on Sunday at the European Society of Cardiology congress in Vienna that Cordaptive, it's extended-release Niacin plus flushing inhibitor, was effective at lowering LDL cholesterol while raising HDL. Reuters has the full story.
• The Observer takes a look at investor unrest at GlaxoSmithKline, and in particular institutions attempts to get their points across to the company's as-yet unchosen new CEO, who will take the reigns when JP Garnier retires in May 2008. You might recall the Telegraph running something along these lines back in May (and our comments at the time on succession speculation). We'll have more to say on this later in the week.
• The Philadelphia Inquirer weighs in on the state of drug marketing, and finds that drug samples and TV ads help drive uptake of medicines.
• Eli Lilly's new schizophrenia drug may offer safety and efficacy improvements over existing antipsychotics, according to results of a 200-patient Phase II trial. From Nature, via the New York Times.
• Acambis has received FDA approval of its ACAM2000 smallpox vaccine

Read More

Another Co-Promote Bites the Dust

When Merck and partner Neuromed yesterday pulled the plug on Phase II chronic pain treatment NMED-160/MK-6721, another co-promote bit the dust, too.

More proof, then, that most co-promote options built into today’s biotech-pharma licensing deals are just window-dressing—comfort cushions for biotech investors dreaming of drug revenues and spec pharma success. Earlier this year we laid out in IN VIVO some of the reasons why fewer than 10% of co-promotes actually turn into market-place reality.

That statistic reassures the Big Pharma partner—most of which hate the thought of sharing their commercial spoils with inexperienced biotech, even if some of them say otherwise. But the main reason co-promote promises don’t often become reality is product discontinuation, as in this case, which helps no-one.

Luckily for Neuromed, the aborted program, an N-type calcium channel blocker, wasn’t its lead. Not since April 2007 anyway, when the biotech licensed US rights to a Phase III extended-release opioid analgesic OROS Hydromorphone from Johnson & Johnson’s Alza.

This deal means Neuromed may yet fulfil its dream, shared with most other biotechs, of setting up its own specialist sales force. And Neuromed may yet get to co-promote products with Merck, since the 2006 deal granted the biotech the option to co-promote to US specialists any N-type calcium channel blockers emerging from the collaboration—and the partners say they’ll keep looking for others.

But with NMED-160/MK-6721 gone, at least in pain, Neuromed will miss out on at least $202 million in milestones, and possibly more. It also paid $30 million up front for OROS. That product had better make it onto the US market (it's approved in Europe, but still not in the US, seven years after an approvable letter ). Otherwise private Neuromed may be in danger of biting the dust, too.

Read More

Insight + Preparation + Dumb Luck = Blockbuster

This blog has spilt plenty of bytes on the nasty consequences for GlaxoSmithKline, and for the industry, of the Avandia problem – but we haven’t said much about who’s likely to benefit. That part of the story we left to The RPM Report – and you can see that analysis here.

As Kate Rawson notes in that story, the two biggest big beneficiaries are Merck’s Januvia – the only DPP4 inhibitor on the market—and Amylin/Lilly’s Byetta. But Januvia is in many ways a more interesting business case study – and one we’ll talk about in a public fireside chat with Merck CEO Dick Clark at Windhover’s annual shindig in New York for the industry’s top business development executives, Pharmaceutical Strategic Alliances.

Clark -- pictured right -- ain't exactly the pin-up CEO. He's a manufacturing guy, from the blue-collar neighborhood of the drug industry. But he's managed a turnaround at the otherwise very white-collar Merck of impressive proportions, this being the company, that not so long ago, looked like a cartoon Gulliver hogtied by thousands of litigious Lilliputions.

And as Clark and I will discuss at the PSA meeting, much of that success is due to Januvia, the product of a nearly perfect blend of scientific insight and strategy, management skill and dumb luck.

Trailing Novartis by four years, Merck’s DPP4 team not only built a molecule that avoided one of the receptor subtypes hit by Novartis’ compound, Galvus, they managed to convince the FDA – although no one is saying so, publicly – that by doing so they’d made a safer drug. Thus Januvia never got hit with the FDA scrutiny Galvus did – and ended up with a safety label so compelling (a side-effect profile comparable to placebo) that this once-a-day pill, noted one diabetologist, has become “the first truly simple-minded therapy in diabetes.”

And probably the fastest beginning-to-end development program for any first-in-class primary-care drug in recent memory (seven years from discovery initiation to approval). Indeed, Clark and research chief Peter Kim had decided – given the company’s thin late-stage pipeline -- that Januvia was one of two drugs (the other was Gardasil, the cervical-cancer vaccine) absolutely crucial to Merck’s recovery from its disaster with Vioxx.

And so Clark created a multi-disciplinary task force around the compound, with its boss reporting directly to him. Bureaucratic hurdles fell away. And the launch was as nearly perfect as a major primary-care launch can be – five months after launch, the drug had captured a greater share of attention (nearly 40%) than nearly any of the recent successful primary-care launches. And it’s now on target for what analysts think could be $775 million in first-year sales.

(We should mention that Clark did the same thing – another multi-disciplinary task force reporting directly to him -- with Gardasil – on track for $1.5 billion in worldwide full first-year sales.)

And then there’s dumb luck. Januvia has been the extraordinary beneficiary of the misfortune of others--the Galvus approval delay, in the first place, and now Avandia. Merck therefore took 100% of the profit from the excitement Novartis helped generate around the arrival of a brand-new anti-diabetic class—but none of the negatives of Galvus’ apparent side-effects. Likewise, it’s taking the lion’s share of Avandia’s lost prescriptions.

And all of this despite the fact that Januvia ain’t that great a drug. Good as an add on. But not particularly powerful in itself. Instead, Januvia is the perfect drug for our era, when safety—particularly mixed with extreme simplicity--sells far better than efficacy alone.

The PSA conference will be a good time to question Clark on just how much a CEO matters in creating a blockbuster. We forecast his answer this way: some -- but dumb luck sure helps.

Read More