2009 -- A Year Of Declines -- In Pharma Brands' DTC Advertising Spend, Too

This, according to Medical Marketing & Media's online site, a few minutes ago -- with the salient New Merck snippet below, but do go read it all:

. . . .Companies lessening their overall expenditure included GlaxoSmithKline, which reduced DTC outlays by about 40% as of September, in line with predictions CEO Andrew Witty had made earlier in the year that the company would do less TV advertising in 2009 than it had in the past.

Merck also reduced spend by nearly 17%, the nine-month data show, reflecting decreased outlay behind its cardio franchise (Vytorin and Zetia) and the HPV vaccine Gardasil, as well as its merger with Schering-Plough. . . .

This trend is likely to persist well into 2010, with "reform" being a watchword in Washington.

Happy New Year, one and all!

And, now a DTC parody redux, from earlier this year:

We bring you -- with no further ado -- Vytorinoxil^®*!



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* Any resemblance in this Holton Sentivan + Gury spot -- to any actually-marketed brand name pharmaceutical. . . . is entirely coincidental. I swear. Cheers!

Could Plea Deal -- In The Galleon Case -- Quickly Lead Us To The Merck, Schering-Plough Inside Traders?

It could well be that this potential deal-cutter will lay bare what I think are the likely connections between the Galleon case, and the ongoing SEC investigation into options and stock trading immediately prior to the Merck-Schering-Plough deal announcement on March 9, 2009.

This guy was high enough up in the scheme that -- if he cuts a deal -- the entire (allegedly) criminal enterprise will be quickly-unmasked. We shall see. Recall that earlier, an ex-Merck patent guy (who had gone on to become a Ropes & Gray patent litigation associate) was arrested, and in highly-sensational fashion, in his office, as the case unfolded.

Per The New York Times legal blog, just a few minutes ago -- do go read it all:

. . . .Anil Kumar, a former McKinsey & Company director accused of leaking information in the Galleon Group hedge fund case, has agreed to waive indictment.

According to a court document filed on Wednesday, the United States attorney’s office in New York said it intended to file more documents related to Mr. Kumar’s case with the court.
Such documents, known as an “information,” typically indicate that some sort of deal has been reached between prosecutors and the defendant.

McKinsey said on Dec. 4 that Mr. Kumar had left the company after being placed on leave.

Earlier this month, Galleon’s founder, Raj Rajaratnam, and an executive at New Castle Funds, Danielle Chiesi, pleaded not guilty to charges of securities fraud after the two were indicted in what prosecutors contended was the largest insider trading ring arrest in history.

Prosecutors had accused Mr. Kumar of providing Mr. Rajaratnam inside information about Advanced Micro Devices, a company Mr. Kumar advised. . . .

To be clear, no current or former Merck or Schering-Plough employee is known to have been named as a target, nor have the companies been implicated in the illicit trading, by the SEC -- thus far. Their bankers and lawyers, on the reverse merger, particularly, on the other hand, have to be considered as among the potential targets of the investigation -- still ongoing.

Pair of Peer-Reviewed Journal Reports Are Critical Of FDA's Medical Device Approval Processes

Significantly, one of the two is co-authored by a current FDA science staffer -- in the Medical Device division.

To be clear, there are important differences between the approval processes for drugs, as distinguished from devices -- such as coronary stents, and pacemakers. Even so, the similarities (and common sense) would tend to suggest that an at least equally robust process be employed, if a device is to be approved, and then permanently implanted inside a patient's body.

Both the Wall Street Journal, and The New York Times have reports out tonight on the two studies -- the small excerpt in blue below, is from the WSJ version; the green, the NYT:

. . . .Jeffrey Shuren, acting director of the FDA's device division, acknowledged weaknesses in clinical trials used to approve some cardiovascular devices. One of the studies was co-authored by an FDA scientist. Dr. Shuren said the FDA has begun toughening standards for device approvals and intends to do more. . . .

One of the articles, published Tuesday in the Journal of the American Medical Association, or JAMA, says many cardiovascular devices are approved based on a single study; most drugs go through several layers of testing.

Many heart devices are implanted in patients and are essential to keeping them alive. They are subject to the FDA's most stringent review process, but the JAMA study said the standards are still weaker than those used for drugs.

"The bar for evidence of benefit should be higher for devices because they are implanted and cannot simply be discontinued, as drugs can," the researchers said in the JAMA paper. . . .

~~~~~~~~~~~~~

. . . .The F.D.A.-sponsored study found that more than 40 percent of the studies used to approve cardiovascular devices had lacked high-quality data about either the treatment or safety goals of the study. In addition, that study also found that about 25 percent of trials had failed to adequately follow the outcomes of a sufficient number of patients, a level the review defined as 90 percent or more of patients initially enrolled in a trial.

“The study’s findings demonstrate that submitted studies frequently lack important details, including information about subjects and study end point definitions,” researchers reported in the review, which was posted Tuesday on the site of The American Journal of Therapeutics.

Dr. William H. Maisel, a cardiologist at the Beth Israel Deaconess Medical Center who was involved in the study, said the review did not find a correlation between lower-quality data and problems related to the devices. However, he said he thought the potential for such links existed. . . .

Do go read all of both, but FDA had already formally-indicated -- at about the time the existence of these (then-ongoing) studies were becoming public -- it would bolster its internal standards and processes, for determining all future approvals of medical devices.

Will Zinc Finger "Scissors" Tools Help Achieve True Gene-Therapy?

In its "Science Tuesday" column today, The New York Times offers yet another provocative glimpse into what may be the future of medicine -- long hoped-for, but until this moment, largely unattainable: specific modifications to a patient's genetic structure. These precisely-targeted changes would be used to fight disease, to boost immunity, or (in perhaps the most ambitious version) to render the patient's DNA impervious to attack from the HIV virus, for example.

[This very optimistic view stands in stark contrast to rather down-beat pieces I profiled in the NYT, earlier, on genetic science to treat disease.]

Do go read it all, but here is a snippet:

. . . .Zinc fingers are essential components of proteins used by living cells to turn genes on and off. Their name derives from the atom of zinc that holds two loops of protein together to form a “finger.” Because the fingers recognize specific sequences of DNA, they guide the control proteins to the exact site where their target gene begins.

After many years of development, biologists have learned how to modify nature’s DNA recognition system into a general system for manipulating genes. Each natural zinc finger recognizes a set of three letters, or bases, on the DNA molecule. By stringing three or four fingers together, researchers can generate artificial proteins that match a particular site.

The new system has been developed by a small biotech company, Sangamo BioSciences of Richmond, Calif., and, to some degree separately, by academic researchers who belong to the Zinc Finger Consortium. . . .

Again, if this pans out, the implications for old-line pill makers could hardly be more profound. Bio-science programs at New Merck (and Pfizer, Sanofi, Amgen and Novartis) seek to be ready, and in a position to capitalize -- should this zinc scissoring "tool-belt" emerge as a feasible way to handle the gene sequence, with precision. To be clear, though, the whole idea of treating at the genetic level, rather than along old-line chemical absorption pathways, is as different from -- and revolutionarily-beyond -- the "old" medicines, as (in transportation) the space-shuttle is. . . to an ox-cart on a rutted dirt path.

^{[Note: My image, at above-right, is highly modified, but the original 3D render was from a public domain wiki-image bank. And so, I declare it too as in the public domain, with my modifications.]}

When Should The Chance Of An Exceedingly Rare Disease Disqualify A Kidney -- For Donation?

That is the fascinating, and difficult question raised in today's New York Times story on two separate kidney-transplant patients that appear to have contracted a very rare infection, from an individual donor-source. [Strictly speaking, this item strays from the core topic this blog covers, as neither Schering-Plough, nor Merck makes any kidney transplantation instrument, kit, device or anti-rejection drug.]

With the well-documented shortages in available kidneys, the questions include risk-to-benefit assessments, as well as informed consent possibilities. Should a donated kidney be implanted -- once the consenting patient is warned of the potential for a disease -- given that it is not really feasible to screen each donated organ for every remotely-possible potential bacterial or other problem? Do go read it all -- as it is quite thought-provoking.

From The New York Times story -- a snippet, then:

. . . .All the tests were negative, so [this donor's] heart, liver and kidneys were transplanted into four patients. Afterward, an autopsy still missed the infection and seemed to support the mistaken diagnosis.

About three weeks after the transplants, both kidney recipients became severely ill, within hours of each other, with seizures, fever and changes in their mental status. They were taken back to the hospital in Jackson. A doctor there noted that both had had kidney transplants the same day. He suspected immediately that the kidneys had come from the same donor and that the donor might have had an undetected infection.

The hospital sent samples of the donor’s brain tissue to the disease centers, which found an amoeba called Balamuthia mandrillaris. One kidney patient was then given a biopsy, which also tested positive for the amoebas. Balamuthia lives in soil and water, and scientists suspect that people become infected through cuts or from ingesting the organism. Only about 70 cases have ever been identified in the United States, and nearly all have been fatal. These are the first known cases from transplants.

It was not clear why only the kidney patients had become ill. The kidneys may have harbored more amoebas than the other organs, Dr. Farnon said, or the particular anti-rejection drugs might have been a factor.

The patients are being treated with “a boatload of drugs,” Dr. Schlessinger said, but have not improved. . . .

I think it likely that the anti-rejection drugs (with their generally salutory by-design immune supression properties -- to decrease chances of organ rejection) were, in part, a cause here. But if the alternative was to die of end stage renal disease, I am perplexed, but leaning toward the notion that this was all a risk worth assuming.

^{[Note: My image, above right, as re-imagined and heavily-edited from a Canadian educational site on medicine, and kidney transplantation.]}

Excessive CEO Pay Correlated With Decreased Stockholder Returns -- Two New Studies

The Wall Street Journal is running an exellent roundup -- on "Top Five Officer" payscales, and in the process, has highlighted two new studies -- one by a Harvard law professor; the other from Purdue's biz school. Both point to the conclusion that excessive officer pay is inversely correlated with total stockholder returns, in future periods.

Confidential Note to Hans Becherer (ex-compensation committee chair of the board, file photo at left) -- Do you now see yourself, when paying CEO Fred Hassan, and his merry band of thugs and robber-barrons, over at Old Schering-Plough, in these results? You should. SGP was wiped from the face of the Earth, due in large part to these excesses. The execesses motivated destructive behaviors. To the Journal, then -- but do go read it all:

. . . . It turns out that the bigger the CEO's slice of the pie, the lower the company's future profitability and market valuation. "These CEOs," says Prof. Bebchuk, "seem to be trying to grab more than they should."

Finance professor Raghavendra Rau of Purdue University and two colleagues looked at CEO pay and stock returns for roughly 1,500 companies per year from 1994 through 2006. They found that the 10% of firms with the highest-paid CEOs produce stock returns that lag their industry peers by more than 12 percentage points, cumulatively, over the next five years.

Companies at the top of the pay pile, Prof. Rau concluded, award their CEOs an annual average of $23 million—but leave their shareholders poorer (relative to other companies in the same industry) by an average of $2.4 billion per year. Each dollar that goes into the CEO's pocket takes $100 out of shareholders' pockets. . . .

Indeed -- some empirical proof of what has felt intuitively obvious, at least to me, for several years now.

While We Wait For the 7 AM EST Senate Healthcare Reform Vote. . .

UPDATED: 12.24.09 @ 8 AM EST -- The measure has passed the Senate 60 to 39; now it is on to reconciliation of the two bills -- House and Senate.

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I thought I'd follow up on the relationships between JP Morgan, Old Schering-Plough, Old Merck, Old Pharmacia, Old Monsanto and the current boards of directors of Celgene (Ex-EVP Carrie Cox, and Ex-JP Morgan banker Robert Hugin), and Amicus (via Ex-Merck Vaccines President Margie McGlynn). This is how boards get built.

Now, let's add in Genzyme's board connections (through Ex-CFO Bob Bertolini). Hey! It's an early Christmas present! Do click around this fine Muckety map -- search it for Genzyme:

. . . .such tangled webs, enjoy. . . .

Okay -- now for some advanced map scoping -- take a look at the below map, it is the old Pharmacia map. Now, drag Fred Hassan's name to the center. Done? Good. Now, double click on Mr. Hassan's name.

Next, drag Schering-Plough to the center. Double click on it. Cool, eh?




Here is the Genzyme map (it needs to be updated for Bertolini's seat):




This one (Celgene) needs to be updated for Carrie Cox's board seat:




Go ahead -- muck around with them. Merry Christmas!

UPDATED: 12.24.09 @ 8 AM EST -- Reform Passes In The Senate, 60 to 39

UPDATED: 12.24.09 @ 8 AM EST -- The measure has passed the Senate 60 to 39; now it is on to reconciliation of the two bills -- House and Senate.

Arena and New Merck Pull The Plug on MK-1903

Apparently, Arena's collaboration with New Merck -- on a new atherosclerosis drug candidate called MK-1903 -- is at an end.

Per Reuters reporting, tonight:

. . . .Merck's decision to pull out from developing MK-1903 came after a mid-stage clinical trial conducted on patients with dyslipidemia failed to meet the primary objective for efficacy, Arena said in a statement.

Merck indicated that the increase of "HDL" or so-called good cholesterol relative to a placebo did not meet the trial's pre-specified objective for efficacy, but did not tie its decision to any safety concerns, Arena said. . . .

Of Celgene's J.P. Morgan Connections -- Carrie Cox's, Too

An astute commenter just inquired after Celgene's interlocks with former Carrie Cox-connected entities. Here is what we've found, thus far: the single common thread that weaves all these companies together (and likely landed Ms. Cox this Celgene gravy-train board seat) is none other than. . . J.P. Morgan.

Perhaps most important J.P. Morgan connection is the oldest precursor of common interlocked relationships: J.P. Morgan was the financial advisor to Pharmacia, in the 2000 deal that bought out Monsanto. Ultimately Pharmacia was sold -- lock, stock and barrel -- to Pfizer. Carrie Cox was with Fred Hassan on both of those deals -- and reaped huge returns, just like Hassan.

More recently, Old Schering-Plough did a lot of banking (advisory) business through J.P. Morgan, and Celgene's current President and COO is a former Managing Director of J.P. Morgan -- and, surprising no one -- J.P. Morgan was Old Merck's financial advisor in the most recent Schering-Plough wipe-out/bust-up:

. . . .Robert J. Hugin has served as our Chief Operating Officer and President since May 1, 2006. He served as our Senior Vice President and Chief Financial Officer from June 1999 until May 1, 2006. Mr. Hugin has served as one of our directors since December 2001. Previously, Mr. Hugin had been a Managing Director at J.P. Morgan & Co. Inc., which he joined in 1985. Mr. Hugin received an A.B. degree from Princeton University and an M.B.A. from the University of Virginia. Mr. Hugin is also a director of The Medicines Company, Atlantic Health System, Inc., a non-profit health care system, and Family Promise, a national non-profit network assisting homeless families. . . .

In addition, the Celgene CEO now serves on the board of Amicus -- where Ex-Old Merck Vaccines President Margie McGlynn just landed (on the Amicus board of directors):

. . . .Sol J. Barer, Ph.D. has served as our Chief Executive Officer since May 1, 2006. Immediately prior, Dr. Barer served as our President, an office he held since October 1993, and as our Chief Operating Officer, an office he held since March 1994. Dr. Barer has served as the Chairman of our Board of Directors since January 2, 2007 and, since March 1994, has served as one of our directors. He is also the Chairman of the Executive Committee of our Board of Directors. Dr. Barer was Senior Vice President—Science and Technology and Vice President/General Manager—Chiral Products from October 1990 to October 1993 and our Vice President—Technology from September 1987 to October 1990. Dr. Barer received a Ph.D. in organic chemistry from Rutgers University and is on the Rutgers Board of Trustees, Rutgers Graduate School Dean’s Advisory Council (Founding Chair) and the Rutgers Bioscience Commercialization Advisory Board. Dr. Barer is also a director of Amicus Therapeutics and serves on the Board of Trustees of BioNJ and the Board of the Brooklyn College Foundation. Dr. Barer previously served as Commissioner of the New Jersey Commission on Science and Technology. . . .

Hmmmm. . . cozy!

25,000 Share Celgene Stock Option For Carrie Cox -- At $51.78

Per a recently filed SEC Form 4, Celgene has already granted Ms. Cox a 25,000 share stock option -- in addition to the annual retainers for directors of the company:

. . . .The Celgene Option will vest and become exercisable in four equal annual installments commencing on December 16, 2010. . . .

At today's NASDAQ closing of $56.29, she is already in the money to the tune of over $112,000. She hasn't shown up for a single tough board meeting (one of seven per typical year; often held at resorts, or other exotic locations); she hasn't filled out an annual D&O questionnaire, yet -- to be named in the proxy -- and she's sitting on $112,000. That's more than many legacy (and soon-to-be) Ex-Schering-Plough employees made for the whole year 2009.

There are several things wrong with this picture.

FDA -- "At Least Vytorin® Doesn't Appear To Elevate Cancer Risk"

Well, that makes me feel so much better (per Reuters) for a direct safety profile -- but not so much, for any future return to growth of the Vytorin^® US revenue stream (as I just observed elsewhere):

. . . .The FDA pronouncement -- while nominally "good news" -- will also remind many anaylsts of the link seen in SEAS -- that is, the increased incidence of cancers, for people on Vytorin, vis-a-vis a placebo.

Now, true-enough, FDA is saying that the SEAS cancer link does not appear, at this time, to be a cause-effect link. However, if the "new" talking point on Vytorin is "Gee, at least we don't THINK it causes your cancer risk to rise, in pursuit of lower cholesterol levels. . ." Well. . . .

Merck is going to have an even tougher time -- on reversing the scrip-writing trends away from Vytorin -- compared to Crestor, Niaspan or Lipitor. None of those ever showed a cancer signal.

And each of those sport outcomes data; Vytorin sports none. . . .

Hurdles Cleared: Two Of Three Votes Now Complete -- On A Watch For Christmas Eve

Per CSPAN2 Live video feed [My earlier perspective on the Senate's measure may be found here]:

. . . .The Senate is now in a series of three procedural votes and currently voting to limit debate on the Democrat's substitute health care bill. . . .

Votes: 60 Aye; 39 No. . . .

Later (5:50 pm EST): Per The New York Times:

. . . .The final vote on the health care legislation had tentatively been scheduled for after 7 p.m. on Thursday because Republicans said they would insist on using up the full 30 hours of debate that are allowed under the rules after a filibuster has been cut off. The debt limit vote had threatened to bring senators back to Washington during the week between Christmas and New Year’s.

The Senate will now hold the last of the procedural votes on health care – to cut off the last Republican filibuster of the bill – on Wednesday afternoon. . . .

I guess the Republicans are finally figuring out that elections have consequences.

More "Pay to Delay"? Or, Mylan's Would-Be Version of Vytorin® -- To Be Considered

This time, it's Mylan Labs -- trying to bring a generic version of Vytorin^® to market. Once again, New Merck has brought suit to halt that possibility -- for at least 30 months. Do go read it all, but the AP's Linda Johnson has the story, here.

Note that Glenmark is already pretty close to bringing a generic version of Zetia^® (Vytorin's sister drug) to market, or at least, close to finishing its patent litigation with New Merck,the topic. [The automatic patent litigation 30 month stay on Zetia expired in October 2009.] In any event, here is a excerpt of the Mylan story:

. . . .Mylan Inc. said Tuesday it being sued by Schering Corp. and MSP Singapore over plans to make a generic version of the cholesterol drug Vytorin.

Mylan asked for Food and Drug Administration approval for a range of doses of Ezetimibe and Simvastatin tablets, or Vytorin. . . .

Nasonex®: "Pay To Delay" Underway -- Or, Legit Patent Beef?

According to this item from the Bloomberg wires yesterday, Merck, as successor to Schering-Plough's interests in the Nasonex^® branded inhaler, have sued Apotex, alleging patent infringement. Apotex seeks to bring a generic version of the drug to market. [The suit, Schering Corp. v. Apotex Inc., Case 09-6373, is now pending in the federal District Court in Newark. I'll keep an eye on it for the readers here assembled.]

So, are these the opening chess-moves, moves already known by Merck to be precursors to an end-game in which Merck pays Apotex to keep a generic version of the Nasonex inhaler off the market for a few more years? Or is this a benign, and legitimate, use of the patent statute to stop an unfairly-equipped interloper -- an interloper named Apotex (arguably) equipped with proprietary technology it does not have the right to wield? Time will tell -- but here is a snippet:

. . . . Merck & Co.’s Schering-Plough unit sued Canadian generic drugmaker Apotex Inc. in an effort to stop a copy of the Nasonex allergy inhaler from being marketed.

Closely-held Apotex is seeking U.S. regulatory approval for the generic which would [allegedly] infringe three of Schering-Plough’s patents. . . .

Stay tuned.

Ex-CDC Head To Lead New Merck's Vaccines Unit

She fills the vacancy created this past summer, when Margie McGlynn, Ph.D. steppeed down from this post -- surprisingly, prior to the bust-up, styled as a reverse merger closing date. [Margie McGlynn herself has since landed softly, taking a seat on the board of directors of Amicus.]

This -- on balance -- looks to be a good thing for Merck's shareholders. Perhaps more importantly, from a global perspective -- she also said she would work to expand "access" to Merck's vaccines -- and that is good for all stakeholders, per Reuters reporting:

. . . .She had led the agency from one crisis to another, including the investigation into the anthrax attacks that killed five people in 2001, the H5N1 avian influenza, the global outbreak of severe acute respiratory syndrome, or SARS, and various outbreaks of food poisoning.

"As a preeminent authority in public health, infectious diseases and vaccines, Dr. Gerberding is the ideal choice to lead Merck's engagement with organizations around the world that share our commitment to the use of vaccines to prevent disease and save lives," Merck Chief Executive Officer Richard Clark said in a statement.

"I am very excited to be joining Merck where I can help to expand access to vaccines around the world," added Gerberding, who will head up the company's $5 billion global vaccine business. . . .

Here's to hopin'. . .

Solid "Deep Dive" -- On Fosamax® -- Via National Public Radio

Do go read the whole article, and check out the graphical timeline side-bar, once there -- but NPR has done the nation a great service here, distilling into plain English all the disparate, and fractured (pardon the pun), current learnings on ostepopenia, and the $3 billlion a year drug:

. . . .Increasingly, bone scientists like Cummings say Fosamax^® — and drugs like it — are not a necessarily a win for most women with osteopenia [not full-blown osteoporosis].

Studies in women with osteopenia show that while Fosamax and similar drugs reduce spinal fractures, the drugs may not reduce other types of bone fractures that are more common in women who have osteopenia, say Cummings and Susan Ott, an associate professor in the department of medicine at the University of Washington.

"There was no difference in the number of [nonspine] fractures you had, whether you took the medicine or a placebo," says Ott. "It does make your bone density go up higher, but the number of fractures is what really matters, and that didn't really change."

And what about the long term?

There are no long-term studies that look at what happens to women with osteopenia who start Fosamax in their 50s and continue treatment long-term in the hopes of preventing old-age fractures. And none are planned.

So Cummings says treatment should start only when fracture risk is significant, bone density is low, or someone already has a spine fracture.

He says the WHO is promoting a new tool called the FRAX, which looks at a variety of factors that influence the risk of fracture. This allows women and their physicians to more accurately estimate their risk of experiencing a disabling bone break.

Ott agrees. And, she also worries that taking these medications long-term — over 10 years or more — might actually make bones brittle.

Ott points to a very small number of case reports about spontaneous breaks in the upper leg, which — though very rare — could be important, she says, given what's at stake. . . .

Indeed -- and, as we reported back in September 2009, that is exactly what some of these Fosamax suits are all about.

The Return of Safe Reimportation -- At Last!

According to a Reuters story tonight, the Obama administration will continue to press for safe prescription drug reimportation -- offering the prospect of lower drug prices to American consumers -- just not as a part of this year's health care reform package. I can live with that:

. . . .The White House pledged on Sunday to move forward on allowing imports of safe prescription drugs from nations like Canada where they are less expensive, but not in the healthcare reform legislation now before Congress.

The pharmaceutical industry's powerful Washington lobbying group backs the healthcare reform legislation that is President Barack Obama's top legislative priority, but its important support for that effort could evaporate if drug imports are included [in that package]. . . .

Excellently maneuvered, indeed.

New Class of Osteoporosis Drugs -- To Compete With Fosamax -- By Mid 2010?

This new drug class, Amgen-developed denosumab, is a potential eventual replacement for Merck's Fosamax. Denosumab, to be marketed under the brand name Prolia, is to be distributed by GlaxoSmithKline in Europe, upon approval. Now that the EMA has given a positive opinion on the candidate, EU approval is projected by mid-2010, per a Friday Reuters story:

. . . .Amgen's keenly awaited new drug Prolia, or denosumab, has been recommended for approval in Europe as a treatment for the brittle bone disease osteoporosis, the European Medicines Agency said on Friday. . . .

Interestingly, in the United States, Prolia^TM is a registered trademark of Cargill -- as a food ingredient -- a soy flour, precisely. So, denosumab will likely carry a different branded name here in the States.

CBO Scores Managers' Amendment As Within Tolerable Limits

Moreover, the non-partisan CBO sees a net-decrease in federal budget deficits attributable to this change in law (compared to the present non-system of health care delivery, of course) -- approaching 0.5 percent of GDP, in the later years of the coming decade.

Um, that's likely to be a deficit reduction of over $1 trillion. More, from the CBO's official government blog:

. . . . Over the 2010–2019 period, the net cost of the coverage expansions would be more than offset by the combination of other spending changes that CBO estimates would save $483 billion and other provisions that JCT and CBO estimate would increase federal revenues by $264 billion. In total, the legislation would increase outlays by $366 billion and increase revenues by $498 billion between 2010 and 2019. . . .

Based on the longer-term extrapolation, CBO expects that inflation-adjusted Medicare spending per beneficiary would increase at an average annual rate of less than 2 percent during the next two decades under the legislation—about half of the roughly 4 percent annual growth rate of the past two decades. . . .

CBO expects that the legislation, if enacted, would reduce federal budget deficits over the ensuing decade relative to those projected under current law -- with a total effect during that decade that is in a broad range around one-half percent of GDP. . . .

One other (tangential) thought: based on my quick reading of it, the measure regarding separated funding (two-check writings, etc.) of insurance premiums for abortion services -- and abortion services, alone -- may well turn out to be unconstitutional. [Some other time, I'll explain in detail, but there may be "no rational basis" (magic words, those) for discriminating against women -- and women only (as men do not need/are not biologically-eligible for this coverage) -- making obtaining coverage of this particular reproductive choice-making irrationally cumbersome]. Ironic.

If so -- in the end, the pro-choice forces will have scored a very-adroit victory, here. The bill already plainly contains a so-called "severability" savings provision. That means if one part is invalidated as unconstitutional, the rest remains intact. Ergo, we get reform -- and we may jettison the invasive fiscal strictures on women's reproductive decision-making.

If so enacted, it would seem that Senator Nelson and Rep. Stupak will not ultimately secure any new governmental controls over the collective American female uterus (via the purse-string power, or otherwise) -- despite all these machinations. And that -- in my opinion -- will be a good thing for American civil liberties, and health care law and policy.

More on the Package -- From President Obama

On a "Patients' Bill of Rights":

. . . .The President calls on the Senate to allow an up-or-down vote, and for those opposing reform to stop using parliamentary maneuvers to drag it out. . . .

It has now been nearly a century since Theodore Roosevelt first called for health care reform. And ever since, nearly every President and Congress, whether Democrat or Republican, has attempted to meet this challenge in some way. A bill for comprehensive health reform was first introduced by John Dingell Sr. in 1943. Sixty-five years later, his son continues to introduce that same bill at the beginning of each session. . . .

Our collective failure to meet this challenge -- year after year, decade after decade -- has led us to the breaking point. Everyone understands the extraordinary hardships that are placed on the uninsured, who live every day just one accident or illness away from bankruptcy. These are not primarily people on welfare. These are middle-class Americans. Some can't get insurance on the job. Others are self-employed, and can't afford it, since buying insurance on your own costs you three times as much as the coverage you get from your employer. Many other Americans who are willing and able to pay are still denied insurance due to previous illnesses or conditions that insurance companies decide are too risky or too expensive to cover.

We are the only democracy -- the only advanced democracy on Earth -- the only wealthy nation -- that allows such hardship for millions of its people. There are now more than 30 million American citizens who cannot get coverage. In just a two-year period, one in every three Americans goes without health care coverage at some point. And every day, 14,000 Americans lose their coverage. In other words, it can happen to anyone. . . .

The time is drawing near -- to cast an up or down vote -- time for Republicans to stand in the way of progress, or agree to get on board the train, and ride with it. But make no mistake, without the sea-change signaled by President Obama's election, this effort would be dead in the water.

60 Votes For Healthcare Reform in the Senate -- Beginning Monday

Not without its rather-noticable warts and moles, but it is finally taking shape, per Reuters, a minute ago:

. . . .The Senate bill would extend coverage to 30 million uninsured Americans, provide subsidies to help them pay for the coverage and halt industry practices like refusing insurance to people with pre-existing medical conditions. . . .

And from the Wall Street Journal, an hour ago:

. . . .Democrats released Saturday a broader amendment to the bill, which includes proposals designed to boost support for small businesses, toughen federal regulatory oversight of insurers, and strengthen provisions intended to curb the rapid growth of health care costs.

Lawmakers were awaiting a formal estimate of the bill's cost from the Congressional Budget Office. An estimate of an earlier version by the CBO found that the bill would reduce the budget deficit by $130 billion over the next decade and extend coverage to some 30 million Americans. . . .

I am not sure that I agree that the bill is a case of "the perfect being the (unintended) enemy of the good" -- but it is, in the broadest sense, what is needed. So -- I say "Huzzah!"

Merck Will Pay $21.3 Million For Schering's Drug Pricing Misdeeds

Great story from Pharmalot -- do go read it all. Here is the settlement agreement, courtesy of Ed's server -- and here is a snippet [I covered the earlier similar Warrick state settlements here]:

. . . .The three lawsuits were originally filed by a whistleblower, Ven-A-Care of the Florida Keys on behalf of California, Florida and the federal government. Schering-Plough also settled Florida and cut a deal with the federal government that involved a $44.5 million payment.

The settlement resolves allegations that Warrick Pharmaceuticals, a subsidiary of Schering-Plough, deliberately inflated the Average Wholesale Prices (AWPs) it reported to California for Albuterol. Medi-Cal sets the reimbursement rates for pharmacies for many of the drugs dispensed to Medi-Cal patients based on the AWPs reported by drugmakers, the statement says.

California pharmacies dispensed Albuterol to patients and were then reimbursed by Medi-Cal. By reporting falsely inflated AWPs, some drugmakers caused Medi-Cal to overpay millions of dollars in pharmacy reimbursement. . . .

Atta' boy, Fred! You did a great job on this one!

Carrie Cox's Non-Compete Lasts One Year -- For $52 Million In Schering-Plough 'Chutes?

Given the significant overlap in fields of endeavor between New Merck and Celgene, I thought it a good idea to set out the non-compete Carrie Cox signed -- back in 2003, when she joined Schering-Plough (from Pharmacia):

. . . .9. Confidential Information and Competitive Conduct.

(a) The Executive shall hold in a fiduciary capacity for the benefit of the Company all secret or confidential information, knowledge or data relating to the Company or any of its Affiliated Companies and their respective businesses, which shall have been obtained by the Executive during the Executive's employment by the Company or any of its Affiliated Companies and which shall not be or become public knowledge or generally known within the pharmaceutical industry (other than by acts by the Executive or representatives of the Executive in violation of this Agreement). After termination of the Executive's employment with the Company, the Executive shall not, without the prior written consent of the Company or as may otherwise be required by law or legal process, communicate or divulge any such information, knowledge or data to anyone other than to the Executive's attorneys or to the Company and to those designated by the Company.

(b) During the Noncompetition Period (as defined below), the Executive shall not, without the prior written consent of the Board (which consent shall not be unreasonably withheld), engage in or become associated with a Competitive Activity. For purposes of this Section 9(b): (i) the "Noncompetition Period" means (A) the period during which the Executive is employed by the Company, plus (B) one year following the termination of such employment only (I) in a Specified Termination as defined in the last sentence of this Section 9(b), or (II) if by the Company for Cause; (ii) a "Competitive Activity" means any venture, enterprise, company, business or endeavor which is in competition with the Company or any of its Affiliated Companies in fields in which the Company and its Affiliated Companies have annual sales of more than $10,000,000; and (iii) the Executive shall be considered to have become "associated with a Competitive Activity" if the Executive becomes directly or indirectly involved as an owner, principal, employee, officer, director, independent contractor, representative, stockholder, financial backer, agent, partner, advisor, lender, or in any other individual or representative capacity with any individual, partnership, corporation or other organization that is engaged in a Competitive Activity. . . . the Executive shall not be considered to violate this Section 9(b) as a result of her complying with law or legal process or as a result of her cooperating with any of her prior employers in connection with litigation relating to matters in which she was substantially involved, provided that (A) the Executive does not receive any compensation for such cooperation, other than reimbursement of her expenses, (B) neither the Company nor any of its Affiliated Companies is a party adverse to such prior employer in such litigation, and (C) the Executive notifies the CEO and the General Counsel of the Company before beginning such cooperation and provides them with any information they may reasonably request, from time to time, regarding such cooperation. A "Specified Termination" means a termination of the Executive's employment by the Executive without Good Reason that occurs before the earlier of a Change of Control or the second anniversary of the Commencement Date (a "Specified Termination"), but only if, within fifteen days after the date that the Company receives the Executive's Notice of Termination, the Company notifies the Executive that it elects for this Section 9(b) to continue to be applicable and that it agrees to pay the Executive, within 30 days after the Date of Termination, in addition to any other amounts or benefits to which she may be entitled under Section 5(c), the amount determined under Section 5(a)(i)(C) assuming the Multiple equals one, and to continue providing benefits to the Executive as described in Section 5(a)(ii) assuming the Multiple equals one. . . .

(e) In no event shall an asserted violation of the provisions of this Section 9 constitute a basis for deferring or withholding any amount otherwise payable to the Executive under this Agreement. . . .

To cut to the chase, here -- Celgene likely has annual sales in excess of $10 million, in each of these overlapping areas (cancer and inflammatory diseases), and we know New Merck does.

So -- just as I asked with regard to Ex-CFO Bob Bertolini's board of directors seat at Genzyme, what exactly did Carrie Cox's perhaps $52 million in 'chute payments, all-in, actually buy for the New Merck shareholders -- in the way of reasonable protections?

Apparently, a large tract of beachfront property in Florida (for Carrie Cox, personally) -- that's about all.

Celgene -- Another Board Seat For Carrie Cox

Another seat -- this time, at Celgene -- another long freight-train of stock grants, retirement benefits and paychecks. So it goes. And again, I wonder about her vast-payout, all supposedly to secure the non-compete -- afterall, Celgene works in the fields of oncology, and inflammatory diseases -- just like New Merck:

. . . .Celgene Corp. announced the election of Carrie Cox to Board. Cox is a member of the Board of Texas Instruments and served on their audit and compensation committees, as well as recently being appointed to the Board of Directors of Cardinal Health. . . .

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. . . .

MSD to Acquire CMO in England: Avecia Biologics; Price Not Disclosed

This deal follows-up on, and completes an earlier collaboration covering specific microbial-derived biologics efforts between the parties:

. . . .Avecia Investments Limited announced that it entered into a definitive agreement by which Merck will acquire the biologics business of the Avecia group through a Merck affiliate, in the U.K. (MSD). Avecia Biologics is a contract manufacturing organization with specific expertise in microbial-derived biologics. Financial details of the transaction were not disclosed. Under the terms of the agreement, Merck will acquire Avecia Biologics Limited and all its assets, including all the company's process development and scale-up, manufacturing, quality and business support operations located in Billingham, UK. In addition to honoring all Avecia Biologics contractual commitments, Merck plans to engage in discussions with individual customers relating to their specific ongoing and future biological process development and manufacturing needs after the transaction is closed. . . .

Closing of the transaction is subject to regulatory approval, as well as other customary closing conditions. The Oligomedicines Business of the Avecia group based in the United States does not form part of this transaction. . . .

Makes sense -- in part, to control the channel, here.

New Vytorin® Warnings -- From FDA, Released Tonight

UPDATED: 12.17.09 @ 8:40 AM EST -- Per Salmon's keen eye:

EM has 10% mortality.

It's also considered a mild form of more serious skin toxicities including Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrosis (TENS).

In SJS, mucus membranes are involved so you have burning in the vagina, mouth, urethra, eyelids etc.. SJS also has 10% mortality. Survivors often have scarring.

In TENS, sheets of skin die and slough off the body. Mortality is 40%.

Salmon

December 17, 2009 8:05 AM

~~~~~~~~~~

Significantly less alarming than the Remicade/Simponi warnings (see below), yet these new FDA warnings are likely to continue to add to the looming government-reimbursement tangles, and more general Vytorin/Zetia sales erosion, in the United States:

. . . .Vytorin^® (ezetimibe/simvastatin) tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – November 2009

ADVERSE REACTIONS
Post-Marketing Experience

erythema multiforme

PATIENT PACKAGE INSERT

What are the possible side effects of Vytorin?

Raised red rash, sometimes with target-shaped lesions. . . .

Ick.

New Boxed Warnings From FDA: On Remicade®, and Simponi®

This might be why Merck's stock price declined on the NYSE, this afternoon, despite being started at "Buy", in a new UBS analysts' research report of this morning (link in drug's brand name is to FDA's updated notice text):

. . . .Remicade^® (infliximab) for IV injection

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – November 2009

BOXED WARNING
Malignancy

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including Remicade.

WARNINGS
Malignancies

Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use in rheumatoid arthritis and other indications. Even in the absence of TNF blocker therapy, patients with rheumatoid arthritis may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.

MEDICATION GUIDE

Updated information pertains to the risk of malignancies in pediatric patients, leukemia in adults, and psoriasis-like lesions associated with use of products within the class of TNF-blockers. . . .

~~~~~~~~

. . . .Simponi^® (golimumab)

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – November 2009

BOXED WARNING
Malignancy

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which Simponi is a member

WARNINGS and PRECAUTIONS
Malignancies

Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age), of which Simponi is a member.

Approximately half the cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression, and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months (range 1 to 84 months) after the first dose of TNF blocker therapy. Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports.

MEDICATION GUIDE
Cancer

There have been cases of unusual cancers in children and teenage patients taking TNF-blocking agents.

For children and adults taking TNF-blocker medicines, including Simponi, the chances of getting lymphoma or other cancers may increase.

People with inflammatory diseases including rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, especially those with very active disease, may be more likely to get lymphoma. . . .

Vytorin also got a less-alarming new FDA warning on the package insert and label -- I'll post that in a moment.

Sunscreen "Battle Royale" Heats Up, Again -- And Just In Time For "Cruise Season"!

The trial date in this massive federal Lanham Act suit-and-countersuit (underway in the Delaware district courts) resembling nothing so much as a celebrity cage-match now draws near. Last night, the parties filed a proposed joint pre-trial order. In October 2009, each of J&J's Neutrogena group, and Merck's Schering-Plough (Coppertone) unit agreed to cease the complained-of adverts, on both sides. But they agreed to do so only until January 31, 2010. I doubt the action will be the subject of a final dispositive order by then. So, the battle may begin anew, as winter cruise season gets underway, in earnest. [Both sides have also agreed to forego money damages, preferring to accept banishment/removals of the allegedly offending ads, instead.]

From the final pre-trial papers, then:

[According to J&J's Neutrogena,] in its television advertisement for Coppertone Sport, Schering [now New Merck] makes three false claims: (i) Neutrogena Ultimate Sport spray users cover themselves with 28% chemical propellant, (ii) Coppertone Sport sprays provide better sun protection than Neutrogena Sport sprays, and (iii) studies prove that Coppertone Sport sprays provide better coverage than Neutrogena Ultimate Sport sprays. . . .

. . . .when a party’s advertising refers to studies or data — a so-called "establishment claim" — the challenger can satisfy its burden of proving falsity by "demonstrat[ing] the tests relied upon [] do not establish the proposition for which they are cited." Syncsort Inc. v. Sequential Software, Inc., 50 F. Supp. 2d 318, 341-42 (D.N.J. 1999), or that such tests are "not sufficiently reliable to permit one to conclude with reasonable certainty that they established the claim made." McNeil-P.P.C., Inc. v. Bristol-Myers Squibb Co., 938 F.2d 1544, 1549 (2d Cir. 1991). . . .

[In response,] Schering alleges that Neutrogena’s advertising is false in three respects: (i) Neutrogena falsely asserts that only products with Helioplex provide protection from UVA and UVB rays, even though the literal words of Neutrogena’s ads state no such thing [(!)]; (ii) Neutrogena falsely asserts that Neutrogena Ultimate Sport is the “Best line of sport sun protection,” and (iii) a bar graph in Neutrogena’s advertising communicate[s] falsehoods. In denying Schering’s motion for a preliminary injunction addressed to these claims, the Court already has determined that none of these asserted messages is a literal falsehood under the Lanham Act. See Schering Plough v. Neutrogena Corp., 642 F. Supp. 2d 304 (D. Del. Aug. 5, 2009) (the "Order"). In the five months since the Court issued the Order, nothing has changed that would render these claims literally false, and Schering has conducted no survey addressed to the Helioplex claims in Neutrogena’s advertising. Schering recently produced a consumer survey that purports to show that consumers took away the message from a Neutrogena Ultimate Sport print advertisement that Neutrogena Ultimate Sport is superior to or more durable than Coppertone Sport. Schering’s survey effectively has no control, is not addressed to the relevant issues, and otherwise fails to establish that Neutrogena’s advertising communicates any implied false messages. . . .

Should be grin-inducing. . . if not tan-producing. Why? Well, the court has already signaled it likely won't side with New Merck -- as noted above ". . .in denying Schering’s motion for a preliminary injunction addressed to these claims, the Court already has determined that none of these asserted messages is a literal falsehood under the Lanham Act."

As I have repeatedly opined, I think this is but a straw-man/proxy for the fight (between the same parties, and filed at about the same time, to boot!) over $8 billion in sales of Remicade and Simponi (via J&J's Centocor unit -- previously distributed outside the US by Schering-Plough), now deep in arbitration proceedings.

Newly-Coordinated Discovery -- In A Slew Of NJ Federal "Enhance Debacle" Cases

As a result of the reverse merger -- and the veritable plethora of pending would-be federal class actions -- alleging various sorts of securities fraud, ERISA violations, civil RICO violations and false-advertising infractions -- Judge Cavanaugh has agreed with the parties in each of these MDL suits (click image at right, to enlarge) that discovery ought to be coordinated.

At first blush, this development would nominally seem to favor New Merck, as it should reduce the number of potentially-duplicating appearances and productions for Lowenstein Sandler (Merck's defense firm).

Upon a closer review, though, I suspect this will benefit the various plaintiff-groups even more than New Merck, and its current and former officers (which term, loosely defined, still includes Hans Becherer, Fred Hassan, Carrie Smith Cox and Tom Sabatino, among others).

How so? Well, now all the various groups of plaintiffs' lawyers will likely share discovery strategy efforts, and share the financial burden of seeking the truth, all while minimizing New Merck's ability to slow-roll the process, by claiming conflicting discovery calendar obligations, or claiming "other duties" preclude the various executives' appearances at depositions, for example.

. . . .for the purpose of pre-trial discovery only. . . . these matters will be coordinated. . . .

New Merck Names "The Fosamax® Guy" As Its New Chief Medical Officer

The guy apparently led the development efforts on Fosamax^® (a drug the subject of over 900 lawsuits alleging jaw bone death, as a side effect of taking it, longer term). Let's hope his instincts have improved since then. I trust he is better than that would suggest -- here is his prior life, in summary fashion:

. . . .Dr. Rosenblatt has served as Dean of Tufts University School of Medicine since 2003. Prior to Tufts University, Dr. Rosenblatt held the appointment of George R. Minot Professor of Medicine at Harvard Medical School and Chief of the Division of Bone and Mineral Metabolism Research at Beth Israel Deaconess Medical Center (BIDMC). He served as the President of BIDMC from 1999-2001. Previously, he was the Harvard Faculty Dean and Senior Vice President for Academic Programs at CareGroup and BIDMC and a founder of the Carl J. Shapiro Institute for Education and Research at Harvard Medical School and BIDMC.

Prior to that, he served as Director of the Harvard-MIT Division of Health Sciences and Technology. And earlier, he was Senior Vice President for Research at Merck Sharp & Dohme Research Laboratories where he co-led the worldwide development team for alendronate (FOSAMAX), Merck's bisphosphonate for osteoporosis and bone disorders. In leading most of Merck's international research efforts, he established two major basic research institutes. He also headed Merck Research's worldwide University and Industry Relations Department.

Dr. Rosenblatt is the recipient of the Fuller Albright Award for his work on parathyroid hormone and the Vincent du Vigneaud Award in peptide chemistry and biology, and the Chairman’s Award from Merck. Dr. Rosenblatt received his undergraduate degree summa cum laude from Columbia and his M.D. magna cum laude from Harvard. His internship, residency, and endocrinology training were all at the Massachusetts General Hospital. . . .

Well, I guess Merck just found a permanent expert witness for its defense of these cases -- and probably cheaper (all-in) than his day-rate, too.

"Deal Of The Year"? If Obfuscation Is The Key Criterion

The generally excellent, and ever provocative In Vivo blog has nominated the Merck-Schering-Plough "Bust-Up, Styled As A Reverse Merger" transaction for its Roger^® award -- the pharma deal of the year 2009. In doing so, it explains that the deal is not as transformative as Pfizer's purchase of Wyeth, and likely only buys some moderate extension of time for Merck, on its patent-cliff -- and finally, that 40 percent of the deal's synergy value will likely come from layoffs and plant closings. And still the editors picked it, as a nominee. Uh-huh.

What In Vivo calls "crafty", I would call borderline sham-transactional ledger-domain -- but that will be for a panel of arbitrators to ultimately decide, if Schering/Merck shot itself in the foot, to the tune of $8 billion in annual revenue (via openly picking the J&J Remicade/Simponi fight, rather than negotiating a settled distribution deal ex-US, in advance of the big deal's announcement), thus:

. . . .The second clever bit was the deal's structure, designed to minimize the chance that Johnson & Johnson comes in to spoil the party. Per the companies' 1998 agreement granting Schering ex-US rights to anti-TNF drugs Remicade (and follow-on Simponi), J&J has a change of control clause allowing it to scoop back those rights in the event that Schering-Plough is taken over. (The two drugs in question are potentially worth up to $8 billion together.)

But technically Schering-Plough isn't being taken over: the deal is a reverse-merger in which Schering is the surviving entity--renamed as Merck. And run by Merck's CEO Dick Clark out of Whitehouse Station, N.J.. . . .

Now okay, J&J has sought arbitration. So that crafty bit may not work out. . . .

Do go read it all -- to my eye, it is sorta' like the bespectacled nerdy kid in the front of the class, admiring the unruly kid in the back, who is forever stealing, via-strong-arm tactics, the others' lunch money. I guess we'll have to wait and see whether the arbitrators force the unruly kid to pay some, or all of that lunch-money back (some $8 billion, annually).

Odd.

[H/T Anonymous, in comments, below -- for the lead.]