Tuesday, August 31, 2010

BayBio's "Revisionist History" -- Of The SEAS Cancer Signal Disclosure Debacle


In a federal securities law class action now pending before the U.S. Supreme Court, a biotech industry trade association out of Northern California has filed a "friend of the court" (or amicus curiae) brief, to suggest that adverse event reporting (when statistically insignificant, and thus not disclosed) ought not (without more) be the basis of securities law liability.

I agree with that general proposition.

However -- in an attempt to butress its arguments -- BayBio (the biotech trade group) significantly mis-states one of its key analytical examples. BayBio uses the Merck-Schering-Plough SEAS cancer signal debacle to suggest that "premature" disclosure of "anecdotes" will not serve the investing, or prescription-consuming, public. The SEAS cancer signal was not "anecdotal", in any sense of the word. The signal was observed during a clinical trial of the drug -- not simply doctors or patients "phoning in" aftermarket adverse event reports. It does a disservice to the Court to imply otherwise. [We have previously discussed various proactive, premptive ways of solving SEAS-like crises.]

Moreover, and perhaps more importantly -- as the below trading chart plainly indicates -- Schering-Plough chose to delay its earnings call, and then chose to announce the SEAS signal in the middle of the NYSE trading session, rather than waiting until close, or seeking a temporary NYSE trading halt. Either of these latter approaches would have allowed for time -- time for calm, rational investors to react to the news, digest it, put it in perspective -- and then react in a measured fashion. What actually transpired was a real time, largely unfounded, panic selling session. In making this particular argument by analogy, BayBio is no "friend of the court" -- it is, in fact, simply misleading the Supremes (click to enlarge) -- note that it was the delay in Schering-Plough's Q2 2008 earnings announcement that started the panic -- not the "SEAS cancer signal news", itself:



Here is the full BayBio amicus brief (a 1.3 Mb PDF file) -- and the relevant snippet -- H/T Ed, at Pharmalot:

. . . .These concerns are anything but inchoate. When doctors and consumers learn of reports of adverse events (particularly from the company itself), they understandably become reluctant to prescribe and use those drugs, even when there is no evidence from scientific studies to support any association between the drug and the adverse event. Judyth Pendell, The Adverse Side Effects of Pharmaceutical Litigation 7 (2003) (in a poll of health care professionals and patients, “[a] sizable number of physicians (43%) have avoided prescribing a particular drug that was appropriate for a patient because they were aware that it might be involved in product liability litigation”). And companies, rather than face potentially staggering liability under United States securities laws, now have an incentive to prematurely disclose such reports, even if it is not scientifically responsible to do so.

For example, rather than wait for a study to be carefully vetted, pharmaceutical companies Merck & Co. and Schering-Plough Corp. announced that preliminary results of a clinical study showed an increased risk of cancer in patients taking Vytorin. Shirley S. Wang & Ron Winslow, More Vytorin Bad News Hits Merck, Schering, Wall Street J., July 22, 2008, at B1. This announcement caused significant same-day declines in the prices of the two companies’ shares. Ibid. A few months later, however, the researchers published the study’s full results, and the FDA concluded it was “unlikely” that Vytorin increases the risk of cancer. Jared A. Fovole, FDA Says ‘Unlikely’ That Vytorin, Zetia Increase Cancer Risk, Dow Jones Newswire, Dec. 22, 2008. Vytorin remains on the market today. . . .

As I said, the ACTUAL DAY TRADING CHART above the pull quote tells a very different story. It was, in fact, the choice of Schering-Plough to delay its earnings announcement, coupled to the choice to disclose results mid-NYSE trading session -- rather than seek a halt in trading -- that "caused" much of the day's decline.

The argument BayBio makes thus proves too much -- by half. The SEAS example suggests that it (as in Matrixx) it is how the issuer handles the disclosure that makes most of the difference -- not a specious concern about a rule requiring disclosure of statistically-insignificant, non-scientific "anecdotes".

Monday, August 30, 2010

"The Fool's" Merck Pipeline Piece -- Saying The Soft Parts, LOUDLY


Over at The Motley Fool tonight, Brian Orelli gets it generally right -- as he looks at New Merck's top four pipeline prospects. What he is absolutely perfectly spot-on about is that pipelines are always only "potentials" -- ones that must be actualized, for revenue to ensue:

. . . .Unfortunately, a pipeline only represents potential. The drugs still need to show positive results in order for that potential to turn into revenue. . . .

Merck's hepatitis C drug Boceprevir works great. The problem is that its competitor, Vertex Pharmaceuticals' Telaprevir, seems to work better. I say "seems to" because neither company has run a head-to-head trial comparing the two. But comparing between trials, Telaprevir was able to cure a higher percentage of patients than Boceprevir.

Boceprevir's last chance at stardom will come when Vertex releases phase 3 data on patients who have already failed a previous treatment. Boceprevir was able to cure 66% of patients in its phase 3 trial in that population. If Vertex and marketing partner Johnson & Johnson can top that number, you can write off Boceprevir. It'll still likely get approved, but won't be a major contributor. . . .

Gee -- where have I heard that before? [Almost two years before.] Yes, I do think Vertex will post better Phase III non-responder numbers than New Merck has.

West Point Facility Apparently Completing Wastewater Pollution Abatement Settlement


Hat tip to Ed Silverman at Pharmalot here -- it seems that back in 2007, Merck's West Point facility was caught befouling the local waterways with an unpermitted bolus of potassium thiocyanate. To settle with the US EPA, and the New Jersey environmental agencies, Whitehouse Station agreed to pay for, and have built, a "tiny bubbles" scrubber system (cost: $850,000) in Upper Gwynedd township. Per The Reporter online (NJ), this morning -- do go read it all:

. . . .Merck & Co. Inc. agreed to purchase and pay for the installation of the system as part of its settlement with state and federal agencies, following an illegal chemical release into Upper Gwynedd Township's sewer system, according to a Dec. 13, 2007, news release from the Pennsylvania Department of Environmental Protection.

Installation of the dissolved oxygen system is almost complete, according to Merck spokeswoman Connie Wickersham.

The company agreed to a settlement of more than $20 million after its West Point facility released potassium thiocyanate into the local sewer system, the release states. . . .

We'll keep you posted -- but this was a dye spill.

Sunday, August 29, 2010

WSJ: Merck US, And Merck Germany -- Combine The Womens' Health Assets Of Each?


It is ironic that a graphic I made a bit ago (smaller graphic, at lower right) -- to highlight the all too common confusion between Germany's Merck KGaA and the US Merck & Co. (wholly unrelated entities) -- may actually now reflect. . . a private equity deal proposal.

Some wags getting ink in the Wall Street Journal tonight are suggesting that Germany's Merck KGaA could combine its birth control and hormone replacement franchises with "our" (U.S.) Merck & Co.'s NuvaRing® (from legacy Schering-Plough via Organon BioSciences), and have a private equity auction of sorts (do go read it all, for context):

. . . .The U.S. Merck offers a trickier prospect. The company certainly hasn't declared its women's health business a noncore asset, but sale rumors have surfaced since the company decided to shut down the former Organon operations in the Netherlands. That plan is opposed by the Dutch employees' council, and a sale might be an alternative to the closure.

Merck & Co's main women's health brands are the contraceptive NuvaRing, with annual sales of around $500 million and double-digit growth, and the infertility treatment Follistim. There has been litigation over NuvaRing's safety in the U.S., however, and Follistim recently lost market exclusivity in the European Union. Its first-half sales fell 2% to $271 million. Those factors could complicate a buyout, even though the U.S. Merck products have much higher sales than the German Merck's portfolio.

The most logical plan for private-equity groups would be to buy both divisions and combine them, thus reaping significant savings by eliminating overlapping sales and other functions. But that would likely entail a price above $2.5 billion — especially considering likely interest from pharma trade buyers — and that would be toward the upper end of leveraged buyouts in the past year.

Still, women's health products are noncyclical and many are hormone-based, leaving them less vulnerable to generic competition, which makes this niche well worth a look. . . .

Probably just idle "wanna-be" deal chatter, but it was New Merck's own Dutch workforce at Organon that first suggested Merck ought to sell the Organon BioSciences operations to another European buyer, rather than close up shop in Oss -- as previously announced. So, we shall see.

Stranger things have happened; in any event, this would be additional after-the-fact empirical evidence that the 2009 Schering-Plough deal was in fact a bust-up, not a merger.

Merck's In The Middle Of An HIV-Drug Patent-Spat -- Between Mylan and BMS


Efavirenz -- manufactured and branded as Sustiva® by Bristol-Myers Squibb (apparently in part under a series of licenses from legacy Merck) is an HIV-1 specific, non-nucleoside, reverse transcriptase inhibitor. It is an AIDS threapy, and the first of the patents covering it expire on August 7, 2012. This drug franchise will generate about $1.3 billion in 2010 worldwide annual revenue for Bristol-Myers Squibb, and some portion of that is likely paid over to Merck, on these patent licenses.

So, Mylan is seeking approval to sell a generic form of Efavirenz, through its Matrix Labs subsidiary. Both Merck and BMS have apparently sent Mylan "covenant not to sue" letters. The import of these letters is to suggest that Merck and BMS won't assert that Mylan is infringing the patents covering Sustiva, in order to slyly prevent Mylan from asserting various alleged technical problems (a 0.6 Mb PDF file) with the patents -- as a way of getting Mylan's generic version onto the US markets, sooner than 2012. The rejoinder is here (a 1.3 Mb PDF file).

We will keep you posted on this one.

Some Think Merck A Safe Bet In (An Admittedly Unlikely) Deflationary Scenario


The Personal Finance section of Sunday's Wall Street Journal is suggesting that -- should a period of sustained price deflation materialize in the United States -- large-cap multinational pharmaceutial manufacturers with high dividend yields might become a bettors' "safe-haven".

While I think the probability of a sustained deflationary scenario is remote, I do think that in such an unusual environment, large pharma would be a pretty safe bet. I think especially-highly of Pfizer, on that score -- with its 4.5 percent current dividend yield (and its very cheap $16 per share price, recently, on the NYSE) -- but the article mentions Merck, with its 4.4 percent yield:

. . . .Some big investors are adding companies in safer businesses and avoiding those relying on discretionary spending, such as automobile, funiture and real-estate companies. "Stocks with a high degree of pricing power should do well, like health care, tobacco, utilities," says Jack Ablin, chief investment officer of Harris Private Bank in Chicago.

Mr. Gross of Pimco cites P&G and J&J as examples of stocks with sizable dividends that also claim dependable cash flows.

Mike O'Rourke, chief market strategist at investment trading firm BTIG, says investors nervous about deflation should focus on pharmaceutical companies that "provide defensive qualities that pay you while you wait for a full economic recovery." Merck, for example, has a dividend yield of 4.4%. . . .

I might bet on either Johnson & Johnson, or Pfizer, before Merck. But that's just my preference for being with No. 1, as opposed to No. 2 -- in a tough market, talkin' there.

Saturday, August 28, 2010

Weekend Trivia & Oddities -- Merck's Job Board Edition


While I was out of town, a kind commenter pointed us to a job opening posted on Merk's-web-hosted employment opportunities pages. The commenter suggested that perhpas Merck should have filled the position before executing the Dutch layoffs (which layoffs have triggered protests and Dutch Works Council litigation).

The commenter is spot on. Here is the title of the job, and its reference number. For obvious reasons, I won't be establishing a login identity at Merck's hosted job board -- so, I cannot post the whole job description -- but if a kind commenter would like to log in, and then copy and paste the full description for Job "GLO000100", I'll set it below. -- DONE! Indeed -- irony, that's for me:

. . . .Leader Europe Canada Communications-GLO000100. . . .

The Leader Europe Canada Communications is a senior communications executive required to lead the planning and execution of internal and external communications strategies for the company across Europe and Canada. Provides direct communications support to the region president and other senior regional executives, and counsels country organizations on local communications activities to build talent and ensure alignment with Global Communications strategies in the following areas: branding and reputation, employee communications, media relations, corporate responsibility and policy communications and incident planning/crisis communications. Works closely with GHH (Global Human Health) Communications to ensure alignment on regionwide product communications initiatives and divisional internal communications strategies. Coordinates on an ongoing basis with MMD (Merck Manufacturing Division) and MRL (Merck Research Labs) communications leadership to ensure that key divisional initiatives occurring at the regional level are well coordinated and supported from an internal and external communications perspective.

Specific responsibilities include:

* Drives the development and coordination of internal and external communication strategies supporting the objectives of the region president, other regional executives, and Global Communications leadership

* Oversees and counsels a team of professionals providing direct support to the region and guides their growth and development

* Counsels senior Merck leaders on communications strategies to improve understanding and support for the company and its business objectives

* Ensures regional and local alignment with Global Communications strategies for reputation management, employee communications, product communications, and media relations

* Drives the adoption of best practices and standard communications processes in the region

Qualifications

* BS/BA degree and 10+ years relevent experience

* Excellent written and verbal communications skills. Understands and effectively communicates across multiple languages and cultures

* English fluency is required; foreign language skills strongly preferred

* Strong understanding of the business and regulatory environment in which Merck competes and communicates

* Demonstrates initiative, strategic thinking and creative problem solving in response to the communications challenges and opportunities faced by the company

* Effectively coaches, counsels and builds teams

* Embodies the Merck Leadership Standards as ambassador, mentor, colleague and senior level communications counselor

* Position can be based in the US or the Europe/Canada region. Regardless of location, a minimum of 30% international travel will be required

August 26, 2010 12:34 PM

Thanks! Erh, "Anyone. . . anyone?" [A la the Ben Stein high school economics teacher cameo, in "Ferris Bueller's Day Off".]

Friday, August 27, 2010

FDA's Q2 2010 "Safety Concerns" List Is Out -- Merck's Implanton® Is A New Addition


Several Merck products have been on this list over the past few years (msot notably, Vioxx®), but Implanton® is new this quarter. Here's a direct link to the FDA's full Q2 2010 Safety Concerns list page.

Thanks to Reuters, we were alerted to the Merck angle in this story, earlier this afternoon:

. . . .The list, which comes out quarterly, covers safety issues that the FDA flagged between April and June. . . .

[D]rugs listed include Merck's birth control Implanon®. . . .

In most cases, the FDA offered few clues into what the concerns were and simply said the agency "is continuing to evaluate this issue to determine the need for any regulatory action."

Merck's cholesterol drug Zocor®. . . [was] also listed [along with others], but the agency has already issued more specific safety alerts on those drugs. . . .

We'll keep you posted.

Over 1,500 Filed Vioxx® Injury Claims In Australia Prior To Deadline


The Brisbane Times is reporting that at least 1,500 Australians have filed claims for compensation from Merck's Australian subsidiary, related to Vioxx® -- which, it is alleged, elevated cardiovascular risks in arthritis patients who used to take the painkiller (it was withdrawn, worldwide in 2004).

Earlier in August, The Sydney (Australia) Morning Herald had reported that 350 claimants had surfaced.

. . . .A total of 1500 people have come forward claiming they have had a heart attack after taking the anti-arthritis drug Vioxx.

The potential claimants were ordered to register by this week with the law firm Slater & Gordon, or directly with the Federal Court, if they intended to join a class action against Merck Sharp & Dohme (Australia), which sold the drug in Australia. . . .

Ealrier this year, we detailed an able Australian trial judge's finding that Vioxx was a "defective product" under applicable Australian law [with additional updates, here]. As ever, we'll keep you up to speed.

Teva Claims Merck Has "Double Patented" Its Levitra® ED Drug


Teva is in the process of bringing a generic form of Merck's (really legacy Schering-Plough's) erectile dysfunction drug Levitra® to market. To slow this process, Schering-Plough/Merck had filed a patent infringement lawsuit in April of last year, adding counts in April of this year, because additional patents had been granted that were arguably germane to the manufacture of Vardenafil Hydrochloride (the agent in Levitra). [Just to remind readers, as comtemplated by the various Hatch-Waxman amendments to the patent statutes, competing manufacturers (like Teva) are allowed to launch generic versions of branded patented drugs, "at risk" -- on the earlier to occur of (1) a favorable outcome in patent litigation, (2) 30 elapsed months from the filing of a patent lawsuit, coupled to FDA approval of an abbreviated new drug application, or (3) the formal expiration of the relevant as-granted patent(s).]

Teva formally answered (a 1 Mb PDF file) the latest complaint yesterday, in the United States District Court for the District of Delaware. Teva asserts, among other defenses and counterclaims, a "double patenting" counterclaim -- essentially saying that Merck cannot file two patents on the very same part of one single invention, solely to improperly extend the life of its desired monopoly-by-patent, thus:

. . . .The claims in the '206 patent are invalid under 35 U.S.C. § 103 because the subject matter claimed therein was described in one or more prior patents or publications. . . .

It is often the case that branded drug manufacturers file additional, later-dated patent applications -- on blockbuster franchise drugs (like Levitra), to delay the arrival of generic competitors (like Teva). In some cases, those later "add-on" patents are of less-than-robust novelty, strength, and/or value. This may be one of those times.

In any event, we'll keep you informed as this matter. . . um, rises. . . erh, progresses.

Tuesday, August 24, 2010

Non-Merck-ified Lawyer, K.C. Lam, Resurfaces -- At Caris Life Sciences -- And A Puzzle Ensues


K.C. Lam is a very good lawyer.

He chose an unusual boss to follow, through much of his career, though.

Mr. Lam worked for the Ex-GC of Schering-Plough, both at Schering-Plough, and before that, at Baxter Healthcare Corporation. In fact, both of them worked as lawyers together, in the Renal division of Baxter, from early 1995 to 1997. Then Mr. Lam's boss became the GC of Baxter's public parent, while Mr. Lam stayed on, in that division. Later he became a business development guy at the US domestic operating level, inside Baxter, just north of Chicago.

So, a working relationship that spanned at least 15 years, has now ended. For the first time -- the "Lamb" (pun intended) has declined to follow the legacy Schering-Plough Ex-GC, as the latter moved on to United Airlines, in Chicago. Instead, Mr. Lam has moved to Texas -- to join Caris Life Sciences. And it turns out that involves another "small world" story -- also connected to Baxter. How so?

Well. . . interestingly, the current Chairman of Caris sold a prior public pharmacy benefit management services company he led (which was ultimately renamed "Advance PCS"), to Caremark. Caremark, in turn of course, was created as a public company by Baxter -- in a $1.2 billion spin-off, back in 1992. Caremark has rolled up numerous of these sorts of benefit/manager companies, over the past two decades or so.

One additional footnote: oddly, Caris's Chairman is apparently personally funding a hard right Christian religious publishing entity in Texas, through a Caris-named investment partnership. What's most unusual is that he is using the Caris imprint and trademark to label this investment. I naturally wonder about whether there is to be any benefit, here, to Caris Life Sciences (and its various shareholders)? I just dunno.

So, that religious publishing entity is called Worthy Media -- its website recites the motto as "Helping People Experience the Heart of God". With the return of Mr. Lam to that fold (pun again intended), the "small world" that is life sciences companies -- um, just got a little smaller. Here is a portion of this morning's Caris Life Sciences press release, in any event, for the record:

. . . ."Caris is extremely well-positioned to capitalize on several trends driving the healthcare market, including increasing partnerships and collaborations, as well as healthcare agenda-setting," said David D. Halbert, Chairman and Chief Executive Officer. "KC Lam's legal acumen and business counsel will be invaluable, as we explore related opportunities both domestically and in global markets."

Mr. Lam brings 25 years of experience providing strategic business development direction and legal guidance to pharmaceutical, biopharmaceutical and medical device companies. He joins Caris Life Sciences from Schering-Plough Corporation, where he was most recently the Group Vice President & Associate General Counsel for the global pharmaceutical business. . . .

Prior to Schering-Plough, he led business development functions at. . . Baxter Healthcare Corporation. . . .

It immediately struck me that the part of that release (bolded, above) that mentioned Caris's capitalizing on "healthcare agenda setting" sounds decidedly more like a PAC, or political action committee quip, than it does a straight-ahead BioScience-business quip. And so, often, the water carrier does return to the well. This seems no exception. Another odd choice -- for a very-bright lawyer.

[I'll be largely off the grid for a few days, both travelling and potentially deal-making.]

Next Bellwether Fosamax® ONJ Trial Date: Graves, On November 1, 2010


Pre-trial summary judgment motions, and motions to exclude certain forms of evidence -- will soon be filed; so, while the $8 million verdict in the last case (Boles II) moves toward the appellate courts, Judith Graves v. Merck, et al., gets underway.

This is the fourth Fosamax® ONJ case (if one counts each of the two Boles trials separately). It will, like all the others, be heard by the very-able Judge John F. Keenan, in the federal district courts in Manhattan (technically called the Southern District of New York), and will march inexorably toward trial during September, thus:

. . . .The deadline for case-specific Daubert and summary judgment motions is September 10, 2010, with oppositions due by September 24, 2010, and replies due by October 1, 2010. Memoranda of law in support of or in opposition to the motions will be subject to a page limit of twenty-five (25) pages and replies will be subject to a page limit of ten (10) pages. Oral argument on the motions will be held on October 12, 2010, at 3:30 p.m.. . .

We'll keep you posted -- there are well-over 1,000 such cases pending around the nation.

"No One Should EVER Assume That. . ."


Gina Kolata, writing for this morning's New York Times, has a nicely-nuanced, well-balanced piece out -- on what patients should take away from the failure of Lilly's most recent Alzheimer's drug candidate.

Beyond the direct narrative there lies a meta-narrative, though -- and this line in particular just screamed out to me (see below). It should serve as a warning -- and lighthouse beacon -- in all clinical trials. Do go read the whole article:

. . . .Most patients entering clinical trials believe they are getting a new treatment that may benefit them, Dr. Baruch Brody [director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine] said. Ethicists call that a "therapeutic misconception," he said, adding, "No one should ever assume that in a clinical trial. . . ."

Indeed. Forewarned is forearmed.

Monday, August 23, 2010

Some "Good PR News" Concerning Merck -- And Its Isentress® HIV Meds


I'll say no more -- simply watch the PSA -- and the story tells itself. Read this GLAAD award nomination story in AdAge:

. . . .While there were no mainstream campaigns of note, national advertisers nevertheless increased their targeted outreach to the LGBT community, with more pharmaceutical, food and travel marketers buying ads in gay-targeted publications and airtime on MTV Networks' Logo channel.

Unilever's Bertolli pasta, Absolut Vodka, Merck and Levi's are the four nominees for outstanding TV campaign for the LGBT market, while Givenchy and K-Y Brand were nominated for outstanding mainstream print campaign. Like mainstream TV, there were no nominated campaigns for outstanding outdoor campaign this year. . . .




For this (provided the price is kept within reasonable reach) Merck is to be commended -- not entirely unlike its Mectizan® river blindness initiative.

Jim Edwards -- On Merck's Mystery "Sinemet® API Supplier": Could It Be. . .?


This morning, Jim Edwards, over at b|Net's "Placebo Effect" has a great story up, on Merck's nearly year-and-a-half-long delay in explaining the limited availability of one of its Parkinsons' disease drugs -- Sinemet® -- around the globe; do go read it all:

. . . .[Merck writes we] did build supply inventory from our original supplier and we are manufacturing using supply from our new supplier. However, the process of identifying, qualifying, and obtaining necessary regulatory approvals that are required to establish a new supply source for an active ingredient is complex and takes time. . . .

We'll keep you posted, but I do wonder whether New Merck will now take the active ingredient manufacturing back in-house, as it re-aqcuires that Cherokee/Riverside API facility (sold about two and a half years ago to a diverse-owned firm). Let's keep an eye on it.

CRO Touts "Innovative Patient Recruitment Strategies" -- As It Hires Merck-ified Patient Recruiter


While I am sure the vast majority of this CRO's employees seek only to place the best patient candidates -- in a completely neutral and above-board fashion -- into these myriad FDA-required clinical trials, this drive for "innovation", coupled to a tightly controlled, marketing department driven study design -- will almost inexorably lead to more of these all-too preventable tragedies. [Additional earlier background here.]

In any event, another honcho at Old Merck has landed softly, per the PR NewsWires site-feed:

. . . .Kendle, a leading, global full-service clinical research organization, today announced the appointment of Jeffrey M. Zucker as Senior Director and Global Head, Patient Recruitment. Zucker will provide global leadership for the development and implementation of innovative strategies to accelerate patient recruitment, improve retention and support the timely and efficient delivery of Phase I-IV clinical development programs for the Company's biopharmaceutical customers. . . .

Zucker brings extensive experience from across the biopharmaceutical industry, including management positions focused on site selection and patient recruitment. In his most recent position, he led global trial optimization efforts for Merck & Co. He also has served as Director of Inpatient Operations at CRI Worldwide and as founder and President of Applied Research Trials, a biopharmaceutical consulting firm focused on improving clinical research trials and processes. Zucker has held leadership positions for Eli Lilly, Princeton Biomedical Research and multiple clinical investigative sites. . . .

. . .Innovative patient recruitment strategies in support of investigative sites have earned Kendle consistent recognition as a CRO of choice. . . .

[From Kendle brochures:]

For a Phase III trial across 26 countries Kendle created a proactive optimization strategy to boost recruitment at slow or non-enrolling sites. Kendle’s extensive experience made rapid implementation possible, leading to a 50 percent increase in patient randomizations within one month. . . .

[And this. . .]

Kendle’s global medical writing team has extensive expertise in producing high-quality protocols, Informed Consent Forms, clinical study reports, regulatory submissions with supporting Integrated Summaries of Safety and Efficacy (ISS/ISE), medical manuscripts, abstracts and patient narratives. . . .

I truly believe clinical trials should be about science, not marketing pitches. I hope the FDA (still) agrees.

Sunday, August 22, 2010

Slightly O/T: Seroquel® Exposé In Forthcoming Mother Jones


First, a sincere hat tip to Dr. Adriane Fugh-Berman at PharmedOut.org, and to The Insider at PharmaGossip, for reminding me about this.

This Mother Jones article should be read -- cover to cover -- by anyone familiar with the sordid history of the "atypical" antipsychotics (paging Salmon!) -- as much of the narrative likely applies to the studies legacy Schering-Plough used to clear New Merck's Saphris® (asenapine). In my estimation, Carl Elliott has a Pulitzer-worthy Seroquel® piece, here -- do go read it all:

. . . .On the surface, the study appeared benign. Its purpose was to compare the effectiveness of three “atypical” antipsychotic drugs, each of which had already been approved by the fda: Seroquel (quetiapine), Zyprexa (olanzapine), and Risperdal (risperidone). The study was designed and funded by AstraZeneca, the manufacturer of Seroquel, and it called for 400 subjects experiencing their first psychotic episode to take one of the three drugs for a year. AstraZeneca called it the “CAFE” study, which stood for “Comparison of Atypicals in First Episode.” The management of the CAFE study had been outsourced to Quintiles, a contract research organization, which was conducting it at 26 different sites. . . .

Yet the cafe study was not without risks. It barred subjects from being taken off their assigned drug; it didn’t allow them to be switched to another drug if their assigned drug was not working; and it restricted the number of additional drugs subjects could be given to manage side effects and symptoms such as depression, anxiety, or agitation. Like many clinical trials, the study was also randomized and double-blinded: Subjects were assigned a drug randomly by a computer, and neither the subjects nor the researchers knew which drug it was. These restrictions meant that subjects in the CAFE study had fewer therapeutic options than they would have had outside the study.

In fact, the CAFE study also contained a serious oversight that, if corrected, would have prevented patients like Dan from being enrolled. Like other patients with schizophrenia, patients experiencing their first psychotic episode are at higher risk of killing themselves or other people. For this reason, most studies of antipsychotic drugs specifically bar researchers from recruiting patients at risk of violence or suicide, for fear that they might kill themselves or someone else during the study. Conveniently, however, the CAFE study only prohibited patients at risk of suicide, not homicide. This meant that Dan — who had threatened to slit his mother’s throat, but had not threatened to harm himself — was a legitimate target for recruitment. . . .

You. Must. Read. It. All.

It is this sort of study-design -- coupled with the schemes in a few states (like New Jersey, and Minnesota, apparently), in which no actual court or judge is involved, before an otherwise presumptively-competent adult is forcibly-held in a psychiatric ward, and then effectively forced onto very powerful medications -- that leads to these more-than-occasionally atrocious outcomes. Outcomes that defy Hippocrates' oath -- outcomes for which (in a reformed system) the treating health care professional must ultimately held responsible, if we are see meaningful changes.

[UPDATED: Apparently, Natasha Singer of The New York Times had written to recommend the above article -- on Friday night, as well. I missed hers -- but it is also a worthy read.]

Saturday, August 21, 2010

Do Watch This -- We Are A Nation Of People -- Not A Body-Corporate. We Are "The People". . .


While you watch it, remind yourselves -- we are the ones referenced in "of, by, and for the people" -- not corporations or other business-entities. These entities are not entitled to vote -- for a reason. They are not the "we" in "We, the people. . ."


. . . .[Republicans have] refused to pass other laws for the accommodation of large districts of people, unless those people would relinquish the right of representation in the legislature, a right inestimable to them and formidable to tyrants only. . . .

The above phrase -- modified just slightly -- is handed to us, from the Declaration that formed this nation. It is both a warning and an exhortation -- to all of us. Sleep not on your rights, lest they, in the passage of time, be no longer yours to freely-exercise.

Well, That Didn't Take Very Long! "What's Next?" Coppertone® Ruling




On Thursday, I asked what would come next, in the ongoing multi-year sunscreen "Battle Royale". Now we know: more discovery. In short, NO immediate injunction in favor of New Merck's Coppertone Ultra-Sport® sunscreen.

No surprise. Click above to enlarge the concluding portion of the memorandum opinion and order entered by the very able Delaware federal District Court Judge Sue L. Robinson, or downloard the whole PDF file. Your choice:

. . . .[New Merck's] motion for a permanent injuction. . . is denied. . . .

So, a third summer tanning season is already peeling off, and fading away. . . and still no clear winner.

My guess would be that each side has now spent close to $15 million in prosecuting, and defending, this Bataan-death-march of litigation. There will be no winners (save the lawyers, who are billing by the hour). It's a scorched skin spectacular -- both sides are willingly burning their skin off, for the prospect of keeping their bones. Ick. I'll keep you informed, just the same.

Friday, August 20, 2010

Merck's $20.7 Billion Patent Cliff (!) Table -- UPDATED, For The Patent Perils Of Vytorin®


Here it is (updated to include Impax's intended incursion into Vytorin®'s markets) -- do let me know, if you see any errors:

Branded
Name
Global Sales
($/Yr)
Compound
Name
Suit/Claim
Filed
30 Month Expiry/
"At Risk" Date
Likely
Competitor(s)

Singulair®$4.3BmontelukastFebruary 2007August 22, 2009aTeva
Vytorin®$1.8Bsimvastatin/ezetimibeAugust 2010November, 2013Impax
Zetia®$2.0BezetimibeMarch 2007October 2009bGlenmark Pharma; Mylan; Teva
Primaxin® $760Mimipenem/cilastatinJanuary 2007September 1, 2009cRanbaxy Labs
Temodar®$950MtemozolomideJuly 2007January 2010Barr Labs (Teva Pharma)
Emend®$264MaprepitantJanuary 2009June 2011Sandoz
Cozaar/Hyzaar®$3.5Blosartan.February 11, 2010dnumerous
Integrilin®$300MeptifibatideFebruary 2009November 2011Teva Pharma
Levitra®$430Mvardenafil HClJuly 2009April 2012Teva Pharma
Fosamax®$1.5Balendronate.Lost exclusivity in 2008Numerous; new drugs: Glaxo & Amgen
Heartgard®$500Mivermectin.Lost exclusivity in 2009enumerous
Frontline®$500Mfipronil.March 2010enumerous
Trusopt/Cosopt®$780Mdorzolamide.Lost exclusivity in 2008numerous
Proscar®$320Mfinasteride.Lost exclusivity in 2006numerous
Zocor®$660Mstatin familyLost exclusivity in 2006numerous
Clarinex®$800MdescloratadineSeptember 2006July 2012fOrchid Pharma
Nexium®$1.4BesomeprazoleOctober 2005May 27, 2014gRanbaxy
TOTALS:$20.7 Billion


~~~~~~~~~~

Note a: Trial completed February 2009; Teva's appeal of trial decision (in favor of patent holders) is now pending; no launch yet, despite window being open since August 22, 2009.

Note b: Trial may begin in Q4 2010; though admittedly unlikely, an "at risk" launch (by Glenmark, most likely) "window" will be open -- and could occur at any time, now.

Note c: By agreement, Ranbaxy may launch September 1, 2009.

Note d: The basic Cozaar/Hyzaar patents in Europe expired in February 2010, and the US patents expire in April 2010. Many likely competitors after those dates.

Note e: Both Frontline and Heartgard -- the core, non-combination Animal Health products -- were off-patent by the end of Q1 2010: Frontline (non-combination product) came off patent in the USA during March of 2010. Heartgard returns from Merial, as half of the New Merial JV; half of the Intervet Frontline sales will go to Sanofi-Aventis, under that same new JV. The sales figures in the above table include only Merck's share of the New Merial joint venture.

Note f: All potential generic descloratadine manufacturers have agreed to a launch suspension until at least January 2012 (Orchid -- the one most likely to launch -- will wait, per agreement, until July 2012), though the permissive "at-risk" launch window first-opened in July of 2009.

Note g: Despite the "at risk" launch window opening in April of 2008, Ranbaxy and Merck (along with partner AstraZeneca) entered a settlement agreement keeping a generic form of Nexium off the market until May of 2014. The United States Federal Trade Commission (the "FTC") is now formally investigating this settlement agreement -- looking into, among other matters, its potential for improper anticompetitive effects. In that regard, Merck and AstraZeneca each received an investigative document demand from the FTC -- in July 2008 -- regarding the settlement agreement with Ranbaxy. Merck is cooperating with the FTC in responding to the document demand.


~~~~~~~~~~

Merck Sues Impax For Infringement, After Impax Files FDA Papers To Market Generic Version Of Vytorin®


Well, it is past time to update my Merck patent cliff chart, anyway (see my next post, for that) -- and here's a $1 billion reason to do so.

Moreover, with comparative effectiveness testing due in the US by about the same time, Vytorin® may be effectively "out-of-runway", before IMPROVE-IT is published in mid-2014 (as I predicted on April 2, 2010). So ends the would be dynasty. A sincere hat tip to theflyonthewall online data aggregator:

. . . .Impax confirms patent challenge relating to Vytorin

Impax Laboratories has initiated a challenge of patents listed by MSP Singapore Co. LLC in connection with Vytorin, 10 mg/80 mg. Impax filed its ANDA containing a paragraph IV certification for a generic version of Vytorin with the FDA. Following receipt of the notice from the FDA that Impax’s ANDA had been accepted for filing, Impax notified the New Drug Application holder and patent owner of its paragraph IV certification. On August 19, 2010, Schering Corporation and MSP Singapore Co. LLC filed suit for patent infringement against Impax in the United States District Court for the District of New Jersey. This action formally initiates the patent challenge process under the Hatch-Waxman Act. Once the ANDA is approved by FDA, Global Pharmaceuticals, Impax’s generic division, will commercialize the products. . . .

[Editors' Subsequent Note: In July 2010, New Merck also sued Mylan, and Teva, for infringement of similar patents, covering the ezetimibe portion of this combo pill -- ezetimibe is presently sold as Zetia®, around the world by New Merck.] Although Vytorin was a $1.8 billion franchise this year -- by about November 19, 2013, or 39 months from now -- it may well be all but gone, due to generic competition.

So, even if, by dint of some dark miracle, IMPROVE-IT is published by mid-2013 -- and reaches a favorable outcome -- after New Merck/Schering-Plough's 0-for-4 record (albeit in other, smaller studies), it likely won't matter -- for more than five months, from June to November, 2013. And remember, it is actually far more likely that IMPROVE-IT won't be published until mid 2014.

Game (effectively) over.