First, go read the largely manufactured "study press release", relating to Saphris® (asenapine) longer-term treatement, v. a placebo. Yes, the dearth of longer-term, peer-reviewed human studies is a signal, but minor compared to what we’ve already discussed. This one is yet to be peer reviewed:
. . . .At the end of the double-blind phase, significantly fewer patients had relapsed with SAPHRIS than with placebo, 12 percent vs. 47 percent (P < 0.0001). In addition, the time to treatment discontinuation for any reason, a secondary efficacy assessment, was significantly longer with SAPHRIS than placebo (P < 0.001). These results were presented at a major European psychiatry congress in Istanbul, Turkey. . . .
Salmon will surely be along shortly, right here.
5 comments:
From clintrials.gov this appears to be study A7501012 titled “To Determine Long Term Efficacy and Safety of Asenapine in Schizophrenic Patient Population”.
It had an enrollment of 702 started in April 2005 and was completed in July 2008. It used patients who needed an antipsychotic (probably had a history of relapsing if they weren’t on one) and had been on antipsychotic for at least 1 year and were stable. They were then switched to open label use of asenapine for 6 months and if they didn’t relapse were then switched to asenapine 5-10 mg BID or placebo for up to 6 months of blinded treatment. Stabilized on asenapine in an unblinded fashion for 6 months and then switched them to either placebo or asenapine and the time to relapse was measured.
So in essence take people who do respond to meds (a small subset), who relapse if they don’t stay on meds, (a smaller subset), give them 6 months to relapse on asenapine and if they don’t (so a smaller subset who really respond well to asenapine) and then take half of those patients off asenapine and wait for the fun begin. This is called an ‘enriched study design’ or as I prefer ‘rigged’.
Now on top of all this the dose is up to double the approved dose so assuming there’s a dose response and since the approved dose is 5 mg, this is another factor that doesn’t reflect the population that asenapine will actually be used in.
What’s noteworthy is the timing of this release coming as it does right before market introduction especially as there are no maintenance studies or approval for maintenance.
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Now if you recall the day before the approvable letter for asenapine was sent last January 13th, the FDA issued guidelines for companies to be able to provide articles promoting off-label use (see http://www.reuters.com/article/domesticNews/idUSTRE50C0QK20090113) and which may be found at http://www.fda.gov/RegulatoryInformation/Guidances/ucm125126.htm. Now the FDA webpage for this guidance was updated on August 6th one week before asenapine was approved on August 13th. Unfortunately I don’t know what the changes were.
Subsequently the approval letter and labeling for asenapine wound up on the FDA website (Drugs@FDA) on Sept 3rd (announced Sept 4). Also on September 4th Psychiatric News the paper of the American Psychiatric Association (APA) ran an article on asenapine on page 2 (pure marketing propaganda in my opinion, and on page 4 ran an article on Managing Depression in Pregnancy essentially pushing treating depressions in pregnancy and psychiatrists and OBGYNs to work together and of course we know there has been a push for especially bipolar depression to be and on page 7 there’s an article on a new policy from the American Academy of Pediatrics for Pediatricians to get involved in mental health screening including recommendations on how to get started screening for mental illness in children.
Now back in the April 2008 Edition of OBSTETRICS & GYNECOLOGY, 2 months before asenapine’s original due date, the American College of Obstetricians and Gynecologists (ACOG) issued a PRACTICE BULLETIN entitled ‘Use of Psychiatric Medications During Pregnancy and Lactation. Essentially indicating psychiatric illnesses were more dangerous than drugs to the fetus and indicating that the newer atypical antipsychotics don’t cause problems. Also at the end of May 2008 the FDA issued new guidelines on labeling for drugs in pregnancy and lactation which Sandy Kweder claimed had been in the works since 1997 (see http://www.usatoday.com/news/health/2008-05-28-fda-drug-labels_N.htm) which is contemporaneous with the FDA pulling phen-fen from the market (Note they also went after ephedra in dietary supplements 2 weeks earlier and went after OTC decongestants in children starting right before asenapine was submitted and current with the review cycle.) This emphasis on pregnancy and lactation was also highlighted by Dr. Andrew Von Eschenbach the FDA commissioner himself (http://www.baltimoresun.com/news/health/bal-te.fda29may29,0,2354633.story). Plus contemporaneously Dr. Von E spoke to the Israeli press (http://www.globes.co.il/serveen/globes/docview.asp?did=1000346796&fid=942) stating that “We have an important commitment to promoting orphan drugs, as well drugs used in pediatrics. But I think the real secret is that we're moving towards a new era in drugs. Instead of thinking about the development of drugs for specific diseases, such as prostate or breast cancer, we're beginning to see products for the body's physical mechanisms, and which resolve all the diseases resulting from them. So for instance, a cardiovascular drug can also treat leukemia, and retinal degeneration. We're moving towards an era where there will no longer be rare diseases or orphan drugs. Instead, there'll be drugs that are part of a medical portfolio." I found this interesting because on the same day 2 weeks earlier that the FDA reviewer wrote his e-mail that asenapine was causing pulmonary arterial hypertension (phen-fen like effect) the FDA granted orphan drug status to Terguride to treat PAH, (http://www.emaxhealth.com/94/22327.htm).
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Now the FDA reviewer supported his concerns about the neonatal effects of asenapine based on cross fostering reproductive and development studies in animals, which are never done unless a company is looking for something. This was then dismissed by the toxicology team leader on June 24th and he attributes them to toxicity to the dam (mother) and claims such effects due to toxicity to the mother are typically seen with antipsychotics. But less than 1 week later on June 30th he indicates that the very same effects with iloperidone, another antipsychotic, are definitely due to the drug and cannot be ascribed to toxicity to the dam (http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022192s000TOC.cfm which is strange because this was right up front you have to assume that it took him at least a few weeks to read and sign off on this huge review. (Told you I found a gold mine with iloperidone.)
I think Sir Walter Scott Marmion said it best ''Oh what a tangled web we weave when first we practice to deceive''
Salmon
Excellent -- these will go to the top of the page, in the morning!
Very-well-done!
Namaste
By the way did anyone else notice that on July 23rd, 2007 the day that President Bush handed over power so he could have a colonoscopy to screen for prostate cancer just happened to coincide with the kickoff of a HHS colon cancer screening initiative with commercials by Jimmy Smits.
Plus that this happened to be right after the FDA had just approved a genetic test for screening for colon cancer. Plus HHS is kicking off a colon ca screening initiative.
President undergoes colonoscopy for colon cancer.
And that July 23rd just happened to coincide with Pfizer's giving $6 million to the Ontario Cancer Center to combat colon cancer http://www.pfizer.ca/english/newsroom/press%20releases/default.asp?s=1&releaseID=291 and that Pfizer's already approved Sutent (http://www.mydeltaquest.com/english/archive-Pfizer-Glaxo-Poised-to-Emulate-Genentech-Cancer) was already a couple of years into clinical trials for colorectal cancer.
Boy there sure are a lot of coincidences with these Pfizer drugs.
Salmon
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