Saphris (asenapine) new schizophrenia, bipolar drug FDA approval soon

The FDA is about to approve a new schizophrenia, bipolar disorder drug , an immediate release (under the tongue) atypical antipsychotic, Saphris . The FDA committee panel meets July 30, 2009 to review documents in a step toward approval.

Addendum: August 14, 2009 FDA approves Saphris --Saphris approved today

Schering-Plough antipsychotic drug found to be safe and effective by regulators -article

From the article

"Although the Division has not yet reached a final conclusion for this application, we generally are in agreement that the sponsor has provided adequate support to suggest effectiveness,” said Thomas Laughren, head of the FDA’s Division of Psychiatry Products, in a memo to the panel included in the review. “We view the safety profile for this product in the populations studied to be qualitatively similar to that observed for other atypical antipsychotic drugs, and to be acceptable."

"Asenapine sales may reach $195 million a year by 2015, Fernandez said. Schering-Plough said in November 2008 that sales of the drug may exceed $1 billion annually. Pfizer Inc. dropped out of a partnership with Akzo on asenapine in November 2006 for undisclosed reasons.

Top category of drugs

The drug would be sold as Saphris, chosen after the FDA decided that the original proposed name, Sycrest, would be too confusing, according to the staff review.

The agency is scheduled to make a decision by Aug. 20. The FDA usually follows its panels’ recommendations, though it doesn’t have to do so.

Antipsychotics topped U.S. drug sales for the first time last year with $14.6 billion in annual revenue, according to IMS Health Inc. in Norwalk, Conn. Top-selling medicines in the group include Eli Lilly & Co.’s Zyprexa, AstraZeneca Plc’s Seroquel and Johnson & Johnson’s Risperdal. All have side effects, including weight gain, muscle spasms and sleepiness. "
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Wikipedia, Asenapine, Saphris

"Asenapine (Saphris) is a new atypical antipsychotic under development for the treatment of schizophrenia and acute mania associated with bipolar disorder by Schering-Plough after its November 19, 2007 merge with Organon International. Development of the drug, through Phase III trials, began while Organon was still a part of Akzo Nobel.[1] Preliminary data indicate that it has minimal anticholinergic and cardiovascular side effects, as well as minimal weight gain. Over 3000 patients have participated in clinical trials of asenapine, and the FDA accepted the manufacturer's NDA on November 26, 2007 for standard review.[2]


Pharmacology
Asenapine shows high affinity (pKi) for numerous receptors, including the serotonin 5-HT1A (8.6), 5-HT1B (8.4), 5-HT2A (10.2), 5-HT2B (9.8), 5-HT2C (10.5), 5-HT5A (8.8), 5-HT6 (9.5), and 5-HT7 (9.9) receptors, the adrenergic α1 (8.9), α2A (8.9), α2B (9.5), and α2C (8.9) receptors, the dopamine D1 (8.9), D2 (8.9), D3 (9.4), and D4 (9.0) receptors, and the histamine H1 (9.0) and H2 (8.2) receptors.[3] It has much lower affinity (pKi <>Asenapine behaves as an antagonist at all receptors.[3]
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The FDA Psychopharmacologic Drugs Advisory Committee meeting briefing book (1067 pages)

"Death from asenapine(Saphris) can come suddenly and without warning in otherwise young healthy individuals due to arrhythmias or strokes." -page 895/1067, June 18, 2008

PDF of 1067 pages, briefing book for the July 2009 FDA Psychopharmacologic Drugs Advisory Committee(meeting materials) at the FDA website, Saphris the atypical antipsychotic-- sublingual immediate release--under the tongue pill. Zyprexa was used in one trial vs. Saphris, yet there was no placebo control in the 40 week trial for bipolar mania(page 403). Proposed regimens 5-10 mg SZ, BP1 10 mg., no water/food for 10 minutes after taking.(page 479)

Page 895/1067

document dated 6-18-2008

"Death from asenapine(Saphris) can come suddenly and without warning in otherwise young healthy individuals due to arrhythmias or strokes with symptoms easily misattributed to something else such as orthostatic hypotension. More likely most serious cardiovascular toxicities are cumulative resulting in a Phen-fen type toxicity especially when dosed for over a year, although symptoms which are likely to be misattributed to something else, (e.g. fatigue) may occur as soon as the first dose."

page 896/1067

document dated 6-18-2008

"With respect to benefit there is insufficient data to presently support use in schizophrenia and as for bipolar disorder the data indicted that only the most severely ill may benefit with a few weeks of treatment but possibly not beyond that. Thus even efficacy in bipolar disorder1 needs to be confirmed.

After further review, this reviewer believes that asenapine(Saphris) is unacceptably dangerous at this time, there was inadequate information submitted to assess safety and such information was expected. There is insufficient information to determine if it will have the effects it purports to as suggested in the labeling.

In conclusion the Food Drug and Cosmetics Act require that asenapine not be approved based on the following subsections and criteria:"....(go to PDF page 896 to continue reading this page)
Ronald Kavanagh, Senior Reviewer, 6-18-2008
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Who is Thomas Laughren?

Thursday, August 14, 2008-soulful sepulcher blog-FDA: Loss of integrity and consumer protection: creating pediatric bipolar disorder, ghostwriting, & C.A.B.F.

Ghostwriting

AHRP-FDA Official Dr.Thomas Laughren ghostwritten articles.(link in my article above)

"We also informed Dr. von Eschenbach that the Alliance for Human Research Protection has located at least three (apparently) ghostwritten articles to which the name of Dr. Thomas Laughren, director of the FDA's Division of Psychiatry Products, CDER, is penned."

"Dr. Laughren has lent his name repeatedly to industry-sponsored reports promoting a commercially-driven public health policy aimed at increasing the use of highly toxic drugs that now carry Black Box warnings about risks of suicidal behavior (SSRIs) and premature death (antipsychotics)."
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My Thoughts

Would you trust the approval of this drug? would you take this drug? what do you think about the study history, and report from one year ago? What are the FDA's ethical responsibilities when approving toxic drugs that potentially shorten life spans and create public health hazards?(disabled, or dead patients) who, or what industry influences their decision to approve a drug such as Saphris?

Thoughts?
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Update: Read Shearlings Got Plowed (click here) for this topic and make sure to read the comment section in that post, unbelievable!

Update: 8-14-09 Shearlings got plowed blog updates the approval