Bapineuzumab not the only news
July 31, 2008 – 12:12 pmThe blogs this week had some chatter about the bapineuzumab results released by Wyeth and Elan, but the big news on Thursday was the offer Bristol-Myers Squibb made for ImClone. The talk about the latter item had not quite made it to the blog level, but followup talk will probably happen for weeks. Looks like the investors who put their faith into the promise of Erbitux are about to have their loyalty repaid. Even though there was not a wealth of talk about the ImClone deal to pick up, bloggers were not silent, offering a the usual flood of other tidbits of information (especially Ed Silverman at Pharmalot, who I regard as a one-man wire service). Late in the afternoon came the news that several senators and Congressmen introduced a bill that would set up a government-sponsored academic detailing program.
Not the best news for bapineuzumab
Wyth and Elan tried to put the best spin possible on the results, but a lot of folks weren’t buying it. Shares of both companies fell on the news. Sarah Rubinstein at the Wall Street Journal Health Blog writes about the results. Ms. Rubinstein notes that the data released by the companies showed that none of the patients — with or without a gene that is a risk factor for Alzheimer’s disease — saw more benefit from a higher dose of the drug than they did a lower dose.
Jacob Goldstein at the Wall Street Journal Health Blog takes note of what the analysts are saying. Although David Hamilton at Bnet stated that Wyeth and Elan were pushing forward with the Phase III study based on “wishful thinking and shoddy statistical analysis,” Mr. Goldstein says, “Wall Street analysts weren’t quite as harsh in their assessments, but they did raise some flags.”
According to Mr. Goldstein, “Citing the lack of a greater effect with higher doses of the drug, among other factors, Cowen’s Ian Sanderson said the data ‘raised unexpected questions’ about the drug. On the other hand, Catherine Arnold of Credit Suisse pointed out that, in the group that seemed to show improvement, the benefit was larger than expected. Deutsche Bank’s Barbara Ryan says the chance of success in the late-stage trial is less than 50%, and notes that the overall risk-benefit profile of the drug look worse now that complete results about side effects from the mid-stage trial have been released.
Dr. Derek Lowe at In the Pipeline said the results, although disappointing, should not have been too surprising. “…well, this is an Alzheimer’s drug,” he says. “That means it comes with all the standard baggage: it’s trying to treat an extremely difficult disease that we don’t understand very well, by a mechanism that no one can be sure will work or is even relevant.
Investors had some reason to be disappointed. Wyeth and Elan were fairly sure that the drug would work better in the patients without the gene that was the risk factor for Alzheimer’s disease, and are structuring the Phase III trials accordingly. But the drug still didn’t show that tremendous of an effect in the patients without the gene, Dr. Lowe says. “On top of that, the drug showed little or no benefit (and more side effects) in the two-thirds of the patients who have the APOE4 alleles, which meant that when all patients in the trial were taken together, improvement over placebo didn’t reach significance,” he says. “And since this trial doesn’t seem to have been designed from the start to distinguish between those different patient groups, that’s the only number that you can take away with any certainty. All the other analyses are ex post facto, and thus carry less weight.”
Looking at the results released this week about another Alzheimer disease drug, Rember, Dr. Lowe tries to dissect the reality behind the breathless news stories. The drug, being developed by TauRx Pharmaceuticals, is methylene blue, most often used to treat urinary tract infections. “If Rember is twice as effective as Aricept, that’s great — except Aricept’s efficacy has never been all that impressive,” Dr. Lowe says. “But that’s still something, considering how the drug is supposed to work.”
Unlike other Alzheimer’s disease drugs, Rember targets neurofibrillary tangles caused by tau protein, and Dr. Lowe observes that perhaps pursuing both tau protein and amyloid plaques are the way for researchers to go, or that maybe amyloid is a dead end and tau is the way to go. “I’m not quite ready to bet that way myself, but it’s definitely not something that can be ruled out,” he says. “I wouldn’t put all my money on amyloid either, at this point. (Boy, am I glad I’m not still working in Alzheimer’s: this sort of stuff is wonderful to watch from the outside, but from the inside it’s hard to deal with).”
Dr. Barbara Martin at Pathophilia points out that Elan’s and Wyeth’s share price rose and fell on the exact same data. “After phase 2 data of bapineuzumab in Alzheimier’s disease (AD) were released on June 17, shares of Elan and Wyeth climbed 10.6% and 4.8%, respectively,” Dr. Martin says. “However, after the same data were presented yesterday at the International Conference on Alzheimer’s Disease (ICAD) in Chicago, the share prices dropped 19.6% and 11.2%, respectively. So what were the differences between the June press release and the meeting presentation? Not a heck of a lot.”
Meanwhile, Rich Meyers at World of DTC Marketing says, “The disconnect between slow, plodding scientific research and the demands of Wall Street are on stark display in the world of Alzheimer’s disease drug development.” “…on one side you have the Street, whose motto, instant gratification takes too long, has led to billions of loses in market caps, and on the other side you have pharma drug development, which is trying to get drugs to market while navigating the maze of regulatory rules and issues,” he says. “Stuck in the middle are the millions of patients who are dealing with, or will shortly be dealing with, Alzheimer’s. Remember these are the same analysts who led this country down the path to the housing crisis by bundling bad loans to sell and then asking for more. You can’t serve two masters.”
Bristol-Myers Squibb: Let’s make a deal
Some anticipated this happening about the time of the refusal to file letter debacle, when Bristol-Myers Squibb tried to restructure its deal with ImClone. At that point, however, acquiring ImClone would have been an extremely risky proposition. Now that Erbitux has had time to prove itself on the market, and investor Carl Icahn shook things up a bit, Bristol-Myers Squibb has made its move. Scott Hensley at the Wall Street Journal Health Blog looks at the offer, starting off by paraphrasing the letter CEO Jim Cornelius sent to Mr. Icahn: “Dear Carl, you were right along. ImClone was worth a lot more than people thought. How about $60 a share and let’s call it a deal? Let’s talk. Sincerely, Jim.”
Mr. Hensley adds, “the deal looks like sweet, if late validation, for Bristol’s early interest in the drug and for financier Carl Icahn’s shakeup of ImClone management two years ago. The proposed price per share is almost twice the value of ImClone’s stock when Icahn took over as chairman in October 2006. Bristol owns about 17% of ImClone already, and the offer represents a 40% premium over ImClone’s average share price over the past month.”
Academic detailing bill gets attention
At PostScript, the Prescription Project blog, the writers urge, “The Congressional Budget Office should score this bill. The House and Senate should pass it quickly. We have neither time nor money to waste.” Mr. Silverman talks about the move here, Mr. Goldstein talks about it here.
DrugWonks’ Peter Pitts was one of the commenters on Mr. Silverman’s item. As you can guess, he’s not happy about it. “Clearly pharmaceutical companies detail because they believe it is in the interest of both the public health and their own commercial imperatives,” he says. “Nothing wrong with that. Self-interest and public interest are not mutually exclusive. But it’s only honest to point out that the government has significant self-interest too — Uncle Sam is the largest ‘payer’ in the nation. So the more drugs these government-funded workers classify as ‘wasteful,’ the more money the government saves. Such a conflict is hardly ‘unbiased.’”
John Kamp of the Coalition of Healthcare Communication e-mailed me with the news. He told me, “Senator Kohl can’t have it both ways. Under the rubric of ‘academic detailing,’ the government tells doctors whatever it wants about drugs, while drug companies only can say what the FDA permits. Such a double standard turns the First Amendment upside down. A double standard on free speech has no place in our society and would be terrible medical policy.”
.Around and about …
At Pharmalot, Ed Silverman suggests where a journalist can find a list of pharma-free experts and relates the back story about the list’s creation. Other tidbits from Mr. Silverman: an analysis of a column in Business Week about Pfizer’s stock being on the upswing; news about the FDA seizure of unnapproved drugs from KV Pharma; a look at a news item that may imply FDA is shooting down me-too drugs; a petition from a consumer group looking at FDA for guidance that would streamline the patient information distributed at pharmacies; FDA losing a lawsuit over wholesaler requirements; a report that says FDA is failing to pursue off-label violations; and the CBS Evening News says vaccine defenders have financial ties to the pharma industry
Mr. Silverman also talks with an expert about the implications of the SEAS trial for Vytorin and what the data actually mean, particularly the incidence of cancer noted in the trial. ““The cancer deaths were a surprising finding and I am skeptical of the effect. However, I am not entirely reassured by the other trials,” Yale University cardiologist Harlan Krumholz told Mr. Silverman. “Although a statistical analysis was not presented, it would seem that this is unlikely due to chance particularly if you do a statistical test that is just assessing whether the drug increases risk (that is, we are not testing for whether it protects against cancer). They do not provide enough information for the audience to make this calculation. It is true that they report that the number of fatal and non-fatal cancers is similar in IMPROVE-IT and SHARP (the two other large Vytorin trials ), but that just means that they had a concerning finding and the data from IMPROVE-IT and SHARP are mixed and do not dismiss the finding.”
And one of the most amusing items posted by Mr. Silverman this week: apparently a contractor working for Novartis was running a brothel from his desk at the drugmaker (the ladies were providing the services out of a vetinarian clinic several miles away). “As you may imagine, Novartis was not thrilled to field questions about Baker’s activities, but did send us a statement saying he is employed by Kelly Temp Services, a company contracted to provide services to Novartis,” Mr. Silverman says. “However, he no longer works there, and the drugmaker maintains that it holds employees and contractors to the highest ethical standards. Novartis also wants us to know it is cooperating with authorities, whose investigation is ongoing.”
At the Wall Street Journal Health Blog, Jacob Goldstein picks up an item from the paper that says John McCain may be the radical on health care in the election. Sarah Rubinstein says Heath Ledger’s accidental overdose at home was part of a rising trend of medication mistakes, according to a study by researchers from the University of California at San Diego published in the Archives of Internal Medicine.
Mark Senak at Eye on FDA assesses the digital literacy of pharmaceutical companies, and he’s not impressed. “There are companies that have opened YouTube channels and other companies that forbid their employees from even accessing YouTube,” he says. “Some companies have blogs while others are afraid to monitor blog content the way they do media monitoring. Companies may be literate marketers, but they are all over the map when it concerns communications technology skills.”
John Mack at the Pharma Marketing Blog says he was only making a joke when he commented that his observations spurred Pfizer into changing a DTC ad for Lyrica. But does offer to give ads a “Mack Seal of Approval.” “My ‘user fees’ are considerably LESS than what the FDA charges and what I offer is more relevant to your bottom line,” he says. “After all, you don’t want to spend millions of dollars on DTC ads that will get dissed on my blog, do you? I’m joking, of course! Or am I?”
Rich Meyers at World of DTC Marketing sees cuts happening to DTC budgets (and ad and marketing people consequently losing their jobs). “These are indeed sad times for marketing and marketing people,” he says. “A lot of this however can be blamed on DTC marketers themselves. Their willingness to “go along” with the program and use the same old reach and frequency methodology with TV and print it partly to blame. Never has an industry needed more change and an infusion of new talent yet remained stagnant. While other advertisers are using social media to make the brand the star of consumer engagement DTC ads and websites continue to push information to consumers and have no interest at all in starting a conversation.”
Jim Edwards at Jim Edwards’ NRx is in agreement with Mr. Meyers that DTC pharma marketing’s glory days are behind us. “For consumers, the mental environment is going to change,” he says. “The days when primetime was filled with drug ads are going to fade from memory, like so many Pepsi Challenge taste tests.”
Also this week, Mr. Edwards wonders if Merck is about to stumble over Gardasil adverse event reports, although he points out just how lousy the adverse events reports actually are. And check him out over at Bnet, blogging about why antiobesity drugs will remain elusive for pharma companies.
The anonymous blogger at Clinical Psychology and Psychiatry: A Closer Look assesses FDA’s approval of the existence of child bipolar disorder. (Philip Dawdy of Furious Seasons posts FDA’s statement here.) “Realistically, I suppose that the FDA’s view is irrelevant — drug marketers and key opinion leaders wield more influence than anyone at FDA when it comes to how physicians view psychiatric diagnoses,” this blogger says, and wonders if the agency can maybe then approve “KOL syndrome,” symptoms of which include, “Hiding blatant conflicts of interest … Writing misleading review articles that falsely tout the efficacy of one or more drugs … Magically converting results that show a product is a dud into results showing that a product is safe and effective …”
Michael McCaughan at the InVivo Blog looks at new drug approvals for the first half of 2008; so far the year is a lot like 2007, and that isn’t good. “So what’s the good news? Well, despite the slow start andFDA’s recent history of slow finishes, we would be willing to be that the agency will in fact beat last year’s NME total,” he says. “Why? First off, the agency has at least 30 pending applications for NMEs with user fee deadlines that fall during the second half of the year.”
Dr. Howard Brody at Hooked: Ethics, Medicine, and Pharma, wonders if the next Congress will overhaul FDA, and looks at a commentary on Medscape about professional medical societies.
Johnson & Johnson made a deal in China for a cosmetics company. Marc Monseau at JNJBTW posts some photos of the Chinese company’s products.
I’d make some comments about items written in DrugWonks this week, but hackers and spambots seem to have taken over the comments pages. Go ahead and click on any item in the blog and you’ll see what I mean. I’ve e-mailed Dr. Robert Goldberg about it. If you do read down the page without clicking on any of the items, though, you will get to see Dr. Goldberg’s comments on Republican Sen. Charles Grassley being “the Joker of American politics.” He’s referring to the plans of Mr. Grassley and Rep. John Dingell, D-Mich., to remake the FDA.
Dr. Daniel Carlat at the Carlat Psychiatry Blog rips into the medical education Eli Lilly and Co. is sponsoring for Zyprexa.
Fard Johnmar of Envisioning 2.0 looks at a report that examines how health information found on the Web affects the doctor-patient relationship. “My belief is that online information is causing Americans to view providers’ advice critically, which in some cases may actually benefit relations between patients and medical professionals,” he says.
If you’ve read the news about the Suffolk County, New York, lawsuit against Schering-Plough that alleges that the company committed indictable acts under RICO, Shearlings Got Plowed has all the details here. Condor says, “There are already other RICO putative class action cases pending against Schering-Plough and Merck, but this is quite significant, in my experienced estimation — as at a minimum, it represents a new level of gravitas in the ENHANCE litigation maelstrom now besieging Schering-Plough …” Condor says. “I’ll keep an eye on this one, for the readership. You may count on it.”
Merrill Goozer at GoozNews and Thomas Sullivan at Policy and Medicine examined a Financial Times article that calls for more serendipity in drug research.
