{"id":53985,"date":"2015-02-04T09:55:56","date_gmt":"2015-02-04T14:55:56","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=53985"},"modified":"2015-02-04T19:35:24","modified_gmt":"2015-02-05T00:35:24","slug":"a-perfectly-good-nap","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2015\/02\/04\/a-perfectly-good-nap\/","title":{"rendered":"a perfectly good nap&#8230;"},"content":{"rendered":"<div align=\"justify\" class=\"small\">I first heard that PHARMA was shutting down its CNS drug development when I read Stephen Stahl let loose with a rant heard far and wide in August 2011 [see <a href=\"http:\/\/1boringoldman.com\/index.php\/2011\/08\/29\/myopia-uncorrected\/\" target=\"_blank\">myopia &ndash; uncorrected&hellip;<\/a>]. So I thought it was ironic that a few days later, I read in the <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21676992\" target=\"_blank\"><font color=\"#004400\">American Journal of Psychiatry<\/font><\/a> about a new Atypical Antipsychotic being introduced &#8211; <strong><font color=\"#200020\">Latuda&reg;<\/font><\/strong> [see <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/09\/27\/ought-to-know-by-now\/\"><em>ought to know by now&hellip;<\/em><\/a>]. On the by-line, that paper had seven <font color=\"#200020\">Sunovion<\/font> employees [manufacturer of <strong><font color=\"#200020\">Latuda&reg;<\/font><\/strong>], one Quintiles employee [a Clinical Research Organization], and two KOLs on the Sunovion payroll [one of whom was a professional medical writer who may have written the paper]. Digging further into the FDA Approval documents, things looked odd from any angle [from <a href=\"http:\/\/1boringoldman.com\/index.php\/2014\/02\/14\/or-both\/\" target=\"_blank\">or both&hellip;<\/a>]:<\/div>\n<ul>\n<div align=\"justify\" class=\"small\"><em>When I started nosing around, I found all kinds of interesting and  strange things. There was wide variability in efficacy among countries  and doses.<\/em><\/div>\n<div align=\"center\" class=\"small\"><em><img decoding=\"async\" border=\"0\" width=\"450\" vspace=\"5\" src=\"http:\/\/1boringoldman.com\/images\/latuda-5.gif\" \/><\/em><\/div>\n<div align=\"justify\" class=\"small\"><em>The <a href=\"http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2010\/200603Orig1s000MedR.pdf\" target=\"_blank\">FDA reviewer<\/a> recommended against approval, but was over-ridden by the FDA committee [see <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/09\/27\/ought-to-know-by-now\/\">ought to know by now&hellip;<\/a>, <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/11\/28\/in-the-shadows\/\">in the shadows&hellip;<\/a>, <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/12\/01\/wait\/\">wait&hellip;<\/a>]. The Director of the FDA wrote a <a target=\"_blank\" href=\"http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2010\/200603Orig1s000SumR.pdf\">special report<\/a>  justifying that action. The &laquo;published&raquo; study was coordinated by the shakiest of clinical research centers [see <a href=\"http:\/\/1boringoldman.com\/index.php\/2011\/11\/30\/hiding-uptown\/\" target=\"_blank\">hiding uptown&hellip;<\/a>, <a href=\"http:\/\/1boringoldman.com\/index.php\/2011\/12\/01\/hiding-uptown-more\/\" target=\"_blank\">hiding uptown [more]&hellip;<\/a>].<\/em><\/div>\n<\/ul>\n<div align=\"justify\" class=\"small\">No matter where I looked, there was something amiss, including Lurasidone bringing up the rear in a comparative meta-analysis of antipsychotic efficacy [<a href=\"http:\/\/1boringoldman.com\/index.php\/2013\/07\/01\/the-mother-of-meta\/\">the mother of meta&hellip;<\/a>]. One thing I recall thinking back then was that the most functional part of <font color=\"#200020\">Sunovion<\/font> was their marketing department. Looking at clinicaltrials.gov, they had already started all of the trials needed to aim for new indications [eg Bipolar Disorder] before even being initially approved for Schizophrenia [see<font color=\"#2f1401\"> <\/font><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/09\/28\/echo-echo-echo-echo-echo-echo-echo\/\"><font color=\"#2f1401\">echo<\/font> echo <font color=\"#6d543d\">echo<\/font> <font color=\"#8c7461\">echo<\/font> <font color=\"#a99485\">echo<\/font> <font color=\"#c6b4a9\">echo<\/font> <font color=\"#d3d4cd\">echo&hellip;<\/font><\/a> and <a href=\"http:\/\/1boringoldman.com\/index.php\/2014\/02\/15\/creepy\/\">creepy&hellip;<\/a>]. They&#8217;d learned the formula for success from their predecessors.<\/div>\n<p>                 <\/p>\n<div align=\"justify\" class=\"small\"><img decoding=\"async\" hspace=\"4\" border=\"0\" width=\"150\" align=\"right\" src=\"http:\/\/1boringoldman.com\/images\/latuda.gif\" \/>I didn&#8217;t give <strong><font color=\"#200020\">Latuda&reg; <\/font><\/strong>much thought after that. I had noticed in their signature <em>before-and-after<\/em> ads that <strong><font color=\"#200020\">Latuda&reg;<\/font><\/strong>&nbsp; apparently moves the part from one side of the head to the other<em> like a mirror<\/em>. So when one of those ads popped up, I always noticed. But otherwise, <strong><font color=\"#200020\">Latuda&reg;<\/font><\/strong> was off my radar. And then it was February 2014, and I looked at the <strong><font color=\"#004400\">American Journal of Psychiatry<\/font><\/strong> and there were two articles about <strong><font color=\"#200020\">Latuda&reg; <\/font><\/strong>Clinical Trials in the same issue <u>and<\/u> there&nbsp; was an <a target=\"_blank\" href=\"http:\/\/ajp.psychiatryonline.org\/doi\/full\/10.1176\/appi.ajp.2013.13091240\">editorial<\/a> about it. You guessed it, a Bipolar Disorder indication. Then, I wrote [from <a href=\"http:\/\/1boringoldman.com\/index.php\/2014\/02\/14\/or-both\/\" target=\"_blank\">or both&hellip;<\/a>]:<\/div>\n<ul>\n<div align=\"justify\" class=\"small\"><em>This month&rsquo;s <strong><font color=\"#004400\">American Journal of Psychiatry<\/font><\/strong>  has two articles reporting clinical trials on Lurasidone [Latuda&reg;] as  either monotherapy [<a href=\"http:\/\/ajp.psychiatryonline.org\/article.aspx?articleID=1763708\" target=\"_blank\">Lurasidone Monotherapy in the Treatment of Bipolar I Depression: A Randomized, Double-Blind, Placebo-Controlled Study<\/a>] or as an adjunct to mood stabilizers [<a href=\"http:\/\/ajp.psychiatryonline.org\/Article.aspx?ArticleID=1763709\" target=\"_blank\">Lurasidone  as Adjunctive Therapy With Lithium or Valproate for the Treatment of  Bipolar I Depression: A Randomized, Double-Blind, Placebo-Controlled  Study<\/a>] in Major  Depressions associated with Bipolar Disorder. The trials were both  sponsored by  Sunovion Pharmaceuticals, were both registered on clinical  trials.gov on the same day, and share a number of their many trial  sites [<a target=\"_blank\" href=\"http:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT00868699\">NCT00868699<\/a> (71 sites) &amp; <a target=\"_blank\" href=\"http:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT00868452\">NCT00868452<\/a>  (55 sites)]. All except the last author for both articles are Sunovion  employees <\/em><em>&laquo;<\/em>7 authors each<em>&raquo;<\/em>&#8230; Dr. Sachs directs a Mood Disorders clinic at  Mass General. Dr. Calebrese directs one at Case Western Reserve. Both  are consultants for Sunovion and multiple other pharmaceutical  companies.<\/div>\n<\/ul>\n<div align=\"justify\" class=\"small\">Both articles were glowing. I remembered how informative the <a target=\"_blank\" href=\"http:\/\/www.accessdata.fda.gov\/scripts\/cder\/drugsatfda\/\">Drugs@FDA<\/a> site had been in looking over the original <strong><font color=\"#200020\">Latuda&reg; <\/font><\/strong>approval in 2011, so I went looking for their new indication, but there was nothing there except the label change in January 2013 adding the new approval. No new Medical Review in sight. I&#8217;d had splendid success with Freedom of Information Act [FOIA] requests to the FDA. Within a couple of weeks, I&#8217;d gotten the package of documents for <strong><font color=\"#200020\">Prozac&reg;<\/font><\/strong>,<strong><font color=\"#200020\"> Paxil&reg;<\/font><\/strong>, and<strong><font color=\"#200020\"> Zoloft&reg;<\/font><\/strong> from earlier requests along the way. So I thought I&#8217;d just put in an FOIA request and find out the back story on the <strong><font color=\"#200020\">Latuda&reg; <\/font><\/strong>indication &quot;creep.&quot; A couple of days later, I was writing this [<a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2014\/02\/20\/44137\/\">on time&hellip;<\/a>]:<\/div>\n<ul>\n<div align=\"justify\" class=\"small\"><em>Tuesday, after a long morning working in the clinic, I was awakened from  a recovery nap by a mid-afternoon phone call. It was the FDA calling.  The lady on the phone told me she&#8217;d seen I&#8217;d made other requests, but  they were for &quot;older drugs&quot; [I wasn&#8217;t liking how this was sounding so  far]. She said it was different for recent approvals. I didn&#8217;t follow  all of what she was saying, but she seemed to be trying to dissuade me  from pursuing my request. She said it had to go through several  processes one of which was &quot;disclosures&quot; and there might be a charge.  Did I still want to stay in the queue? By this time I was awake enough  to say, &quot;Sure. How long is the usual wait?&quot; She said &quot;18 to 24 months.  You know, we get over 3000 requests every year.&quot; long pause. I  said &quot;Okay&quot; [having given up with taking out my frustrations with big  systems on small bureaucrats long ago]. But when I was fully awake and  thought about it, I think I learned something, and have to revise my  theory. My now fading enthusiasm for the FDA had been based on  experiences where what I was requesting was old hat, and just required  copying a disk from somebody else&#8217;s previous request. The fantasy that I  could get the information on a recent approval in a timely fashion was  naive. This drug is going to be well down the line in it&#8217;s patent life  before I ever see that report, just like before.<\/em><\/div>\n<\/ul>\n<div align=\"justify\" class=\"small\">So why am I writing about <strong><font color=\"#200020\">Latuda&reg; <\/font><\/strong>right now? It&#8217;s because a reminder I set a year ago on my calendar after that phone call popped up to let me know that my FOIA request went in a year ago this month [and so far, silence from the FDA]. I&#8217;m not grandiose enough to think that the FDA has people sitting around poised to respond to my every whim. So I&#8217;m not surprised at the year of silence. And my calendar is dutifully set for another reminder at this time next year [which will be the advertised &quot;24 months&quot;]. And I recognize that my earlier successes were on older drugs that have probably been requested by big law firms involved in all the legal wranglings about <strong><font color=\"#200020\">Prozac&reg;<\/font><\/strong>,<strong><font color=\"#200020\"> Paxil&reg;<\/font><\/strong>, and<strong><font color=\"#200020\"> Zoloft&reg; <\/font><\/strong>and were already available. So I&#8217;ll wait patiently to see if the information about the indication sprawl for <strong><font color=\"#200020\">Latuda&reg; <\/font><\/strong>ever reaches our North Georgia mountains for me to peruse.<\/div>\n<p align=\"justify\" class=\"small\">There&#8217;s a point to this narrative. I went looking for how <strong><font color=\"#200020\">Latuda&reg; <\/font><\/strong>was doing on the market. What about sales? That took me to various business sites, and somewhere on that road I read that <strong><font color=\"#200020\">Latuda&reg; <\/font><\/strong>prescriptions were up 29% since the Bipolar approval. I finally ended up on the <a href=\"http:\/\/www.ds-pharma.com\/index.html\" target=\"_blank\">Dainippon Sumitomo Pharma Co., Ltd.<\/a> site [Sunovion is owned by this Japanese firm]. And going through the yearly financial reports, I came up with this table [ballpark figures]:<\/p>\n<table cellspacing=\"0\" cellpadding=\"0\" border=\"0\" width=\"150\" align=\"center\">\n<tr>\n<td align=\"center\" class=\"small\"><strong><font color=\"#200020\">YEAR    <\/font><\/strong>      <\/p>\n<hr size=\"1\" \/><\/td>\n<td align=\"center\" class=\"small\">\n<div align=\"right\"><strong><font color=\"#200020\">US SALES     <\/font><\/strong><\/div>\n<hr size=\"1\" \/><\/td>\n<\/tr>\n<tr>\n<td align=\"center\" class=\"small\">2011<\/td>\n<td align=\"right\" class=\"small\">$60 M<\/td>\n<\/tr>\n<tr>\n<td align=\"center\" class=\"small\">2012<\/td>\n<td align=\"right\" class=\"small\">$136 M<\/td>\n<\/tr>\n<tr>\n<td align=\"center\" class=\"small\">2013<\/td>\n<td align=\"right\" class=\"small\">$385 M<\/td>\n<\/tr>\n<tr>\n<td align=\"center\" class=\"small\">2014<\/td>\n<td align=\"right\" class=\"small\">$740 M<\/td>\n<\/tr>\n<\/table>\n<p align=\"justify\" class=\"small\">It looks like it&#8217;s headed for &quot;Blockbuster&quot; status next year [$1 B\/YR]. So here&#8217;s a late-comer that dribbled out of the pipeline just as the spigot was being turned off. It&#8217;s competing with its atypical predecessors and the first generation antipsychotics, all of which are available as less expensive generics. And it&#8217;s at the bottom of the efficacy list in the only meta-analysis that I know of that includes it [see <a href=\"http:\/\/1boringoldman.com\/index.php\/2013\/07\/01\/the-mother-of-meta\/\" target=\"_blank\">the mother of meta&hellip;<\/a>]<\/p>\n<p align=\"justify\" class=\"small\">:<\/p>\n<p align=\"center\" class=\"small\"><img loading=\"lazy\" decoding=\"async\" height=\"266\" border=\"0\" width=\"400\" src=\"http:\/\/1boringoldman.com\/images\/antipsych-1.gif\" \/><\/p>\n<p align=\"justify\" class=\"small\">And yet it got through the FDA with an 11th hour intervention by the FDA Director. It had three published Clinical Trial articles and an editorial that made it into the prestigious <strong><font color=\"#004400\">American Journal of Psychiatry<\/font><\/strong>. So it seems to be having an unusually charmed life, and is selling like hotcakes. As I said, these Sunovion people really seem to know how to sell some drugs [<a href=\"http:\/\/www.mmm-online.com\/sales-force-report-a-walk-on-the-sales-side\/article\/317591\/\" target=\"_blank\">Sales Force Report: A Walk on the Sales Side<\/a>].<\/p>\n<p align=\"justify\" class=\"small\">That point I said I was aiming for is that while <strong><font color=\"#200020\">Latuda&reg;<\/font><\/strong> is zooming up the ladder in sales and usage, I&#8217;m measuring my ability to find out about its safety and efficacy literally in years. So long as that&#8217;s the case, it&#8217;s going to be the pharmaceutical industry&#8217;s sales force that will exert the major influence on which drugs are prescribed &#8211; rather than the plain clinical facts. There&#8217;s no reason in the world for the FDA data seen by the reviewers to need anything except a postage stamp to get it to anyone else qualified to take a look. If there&#8217;s commercially confidential information on a drug, don&#8217;t put it in the material submitted. If there&#8217;s data that needs to be anonymized, do it before the submission. The FDA has more important things to do than calling some old man in the middle of a perfectly good nap to try to talk him out of wanting what he wants. Leave the keeping secrets business for the people in Langley Virginia where it makes sense&#8230;<\/p>\n<hr size=\"1\" \/>\n<p align=\"justify\" class=\"small\"><em><strong><font color=\"#200020\">Afterthought<\/font><\/strong><\/em>: When I looked back over this, I realized I left out something that belongs here. I think <font color=\"#200020\"><strong><em>new<\/em><\/strong><\/font> has a high value. There are plenty of patients who have cycled through many of the available meds and are shopping for <em><strong><font color=\"#200020\">something new<\/font><\/strong><\/em>. And <strong><font color=\"#200020\">Latuda&reg;<\/font><\/strong> came after an empty space &#8211; was the last <em><strong><font color=\"#200020\">something new<\/font><\/strong><\/em> on the block punctuating the <em><font color=\"#200020\">dry pipeline<\/font><\/em> meme. And I would recommend reading that article on <em><strong><font color=\"#200020\">drug rep technology<\/font><\/strong><\/em> [<a href=\"http:\/\/www.mmm-online.com\/sales-force-report-a-walk-on-the-sales-side\/article\/317591\/\" target=\"_blank\">Sales Force Report: A Walk on the Sales Side<\/a>]&#8230;<\/p>\n<div align=\"center\" class=\"small\"><img loading=\"lazy\" decoding=\"async\" height=\"129\" border=\"0\" width=\"519\" src=\"http:\/\/1boringoldman.com\/images\/atypicals-1.gif\" \/><\/div>\n","protected":false},"excerpt":{"rendered":"<p>I first heard that PHARMA was shutting down its CNS drug development when I read Stephen Stahl let loose with a rant heard far and wide in August 2011 [see myopia &ndash; uncorrected&hellip;]. So I thought it was ironic that a few days later, I read in the American Journal of Psychiatry about a new [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[5],"tags":[],"class_list":["post-53985","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/53985","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=53985"}],"version-history":[{"count":60,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/53985\/revisions"}],"predecessor-version":[{"id":54045,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/53985\/revisions\/54045"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=53985"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=53985"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=53985"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}