{"id":28888,"date":"2012-10-12T17:20:18","date_gmt":"2012-10-12T21:20:18","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=28888"},"modified":"2012-10-12T23:41:37","modified_gmt":"2012-10-13T03:41:37","slug":"deja-vu-5","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2012\/10\/12\/deja-vu-5\/","title":{"rendered":"d\u00e9j\u00e0 vu&#8230;"},"content":{"rendered":"<div align=\"justify\">I was scanning through older posts looking for something. I stopped on the one about Solanezumab for Alzheimer&#8217;s [<strong><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2012\/10\/10\/show-me-the-data\/\"><u><font color=\"#200020\">SHOW ME THE DATA!&hellip;<\/font><\/u><\/a><\/strong>] and my eyes lingered on the titles of the two articles I&#8217;d listed:         <\/div>\n<ul><sup>          <\/p>\n<li>\n<div><a href=\"http:\/\/www.fiercebiotech.com\/story\/eli-lilly-surges-mixed-secondary-data-alzheimers-drug-solanezumab\/2012-10-08\" target=\"_blank\"><strong><font color=\"#200020\">Eli Lilly surges on conflicting data for Alzheimer&rsquo;s drug solanezumab<\/font><\/strong><\/a><\/div>\n<\/li>\n<li>\n<div><a href=\"http:\/\/www.fiercebiotech.com\/story\/eli-lilly-surges-mixed-secondary-data-alzheimers-drug-solanezumab\/2012-10-08\" target=\"_blank\"><strong><font color=\"#200020\">Experimental Lilly drug may help slow mental decline in people with mild Alzheimer&rsquo;s disease<\/font><\/strong><\/a><\/div>\n<\/li>\n<p>           <\/sup><\/ul>\n<div align=\"justify\">I forgot what I was looking for because my mind was full of another thought &#8211; &quot;<em>I&#8217;m having <span class=\"st\">d\u00e9j&agrave; vu<\/span>!<\/em>&quot; Here&#8217;s the essence of what those articles said for a reminder &#8211; the first article:<\/div>\n<blockquote>\n<div align=\"justify\"><sup><strong>As Lilly  conceded earlier, both of its late-stage studies for  solanezumab failed  to produce a statistically significant response for  mild-to-moderate  patients on two key endpoints. Simply put, the study  failed. But after a  secondary analysis of the first study showed that  there was a 42%  reduction in the rate of cognitive decline among a  subpopulation of  patients in the solanezumab arm with only a mild form  of the disease,  investigators decided to hunt for confirmation of that  endpoint in a  second Phase III. They didn&rsquo;t find it, seeing the numbers  fall short of  statistical significance after switching from one  measure [ADAS- Cog11]  to another [ADAS-Cog14]. But by &quot;pooling&quot; the  data they came up with a  34% reduction in cognitive decline in that  particular group. None of the  data indicated a significant reduction in  the rate of functional  decline.<\/strong><\/sup><\/div>\n<\/blockquote>\n<div align=\"justify\">and the second:      <\/div>\n<blockquote>\n<div align=\"justify\"><sup><strong>The main measures were two tests &mdash; one reflecting language, memory and  thinking and the other, ability to perform daily activities such as  eating and grooming. The combined results on the mild disease patients  showed a nearly 2-point difference in the roughly 90-point score on  thinking abilities. Previous studies suggest that a change of 3 to 4 on  the score is needed to show a clinical benefit, like an improvement in  how well patients can take care of themselves.<\/strong><\/sup><\/div>\n<\/blockquote>\n<div align=\"justify\">Those things are completely crazy! Talk about massaging the numbers! They massaged and massaged, and found nothing. Finally, by pooling the two studies together, they came up with a massage technique that vaguely went in the direction they wanted. They had preordained that they needed something like a 4% improvement for success, and even with all the massage, they ended up with only 2%. No way to call that anything but a failed study. As a matter of fact, this is what they said a month ago:<\/div>\n<blockquote>\n<div align=\"center\"><a target=\"_blank\" href=\"http:\/\/www.fiercebiotech.com\/story\/breaking-lillys-solanezumab-flunks-out-latest-alzheimers-debacle\/2012-08-24\"><u><strong><font color=\"#200020\">Lilly&#8217;s Alzheimer&#8217;s drug solanezumab flunks out, but CEO sees promise<\/font><\/strong><\/u><\/a><br \/>      <strong><font color=\"#200020\">FierceBiotech<\/font><\/strong><br \/>      By John Carroll<br \/>      August 24, 2012      <\/div>\n<p>      <\/p>\n<div align=\"justify\"><sup><strong>After enduring months of criticism about its late-stage effort to determine the efficacy of the last big Phase III hope for Alzheimer&#8217;s, Eli Lilly this morning announced that solanezumab flunked both primary endpoints. The failure, widely forecast by a long lineup of analysts, will raise more doubts about the theory that cutting levels of toxic amyloid beta in patients with mild to moderate Alzheimer&#8217;s can help patients with the disease.<\/p>\n<p>      Lilly, though, isn&#8217;t giving up on the drug, its second major try at treating Alzheimer&#8217;s. CEO John Lechleiter, who has bet his job that the company&#8217;s R&amp;D division can develop a new generation of therapies, noted that a secondary analysis of pooled data &quot;showed statistically significant slowing of cognitive decline in the overall study population of patients with mild-to-moderate Alzheimer&#8217;s disease. In addition, pre-specified secondary subgroup analyses of pooled data across both studies showed a statistically significant slowing of cognitive decline in patients with mild Alzheimer&#8217;s disease, but not in patients with moderate Alzheimer&#8217;s disease.&quot;<\/p>\n<p>      &quot;We recognize that the solanezumab studies did not meet their primary endpoints, but we are encouraged by the pooled data that appear to show a slowing of cognitive decline,&quot; said Lechleiter in a statement. &quot;We intend to discuss these data with regulatory authorities to gain their insights on potential next steps.&quot; Expectations for this trial were so low that Lechleiter&#8217;s hopeful note apparently captured the attention of investors, who initially pushed up shares of the company by 5% in early trading&#8230;<\/strong><\/sup><\/div>\n<\/blockquote>\n<p align=\"justify\">This is what has been wrong with the whole psychopharmacology scene for the last thirty years! Having put so much effort into some drug, they just can&#8217;t let it go when it doesn&#8217;t work. So if they can find anything positive, even if they have to roll it around with their statistical package for a month, they start turning cartwheels. Not because the drug is going to do anything much for people with Alzheimer&#8217;s disease, but because they know that if they can get it approved by the FDA for Alzheimer&#8217;s, they can sell it to the people who are watching their aging parents deteriorate in front of their eyes. All they have to say to sell it is &quot;<strong><font color=\"#200020\">Solanezumab may slow the progression of Alzheimer&#8217;s disease<\/font><\/strong>&quot; or &quot;<strong><font color=\"#200020\">FDA Approved for Alzheimer&#8217;s disease<\/font><\/strong>&quot; or <strong><font color=\"#200020\">&quot;Ask your doctor if Solanezumab is right for her<\/font><\/strong>.&quot; I can see it now. Some attractive elderly woman who was sitting in a rocking chair staring in the first frame is out pushing her blond granddaughter in a swing with a big smile in the second. There were no cases remotely like that in the whole study!<\/p>\n<div align=\"justify\">Here&#8217;s the d\u00e9j&agrave; vu part, it&#8217;s the same thing that happened with Paxil Study 329. They got a dismal report on the trial, but after a thorough massage by a professional masseuse named Sally, they found a way to jury-rig the numbers. In that case, it was already on the market so they didn&#8217;t have to go through the FDA &#8211; they just sold it by word of mouth. If they can get it&nbsp; to market, they can sell it to the desperate people who will try anything and pay almost any price. The market is that hungry &#8211; still. People hate to see their kids depressed just like they hate watching their parents deteriorate with Alzheimer&#8217;s. And here&#8217;s another similarity with Paxil Study 329. In that study, neither subject nor parent ratings showed any difference with the treatment. In these studies of Solanezumab, &quot;<em>None of the  data indicated a significant reduction in the rate of functional  decline.<\/em>&quot; They got nothing. So that&#8217;s why I wrote:<\/div>\n<blockquote>\n<div align=\"justify\"><sup><strong><em>&quot;It&rsquo;s telling that &#8216;The  $60 billion question here is whether Eli Lilly and its science  team   has the kind of data indicating that they are on a solid path to an    approval&#8217; rather than &#8216;Does it work in Alzheimer&rsquo;s Disease?&#8217; &quot;<\/em><\/strong><\/sup><\/div>\n<\/blockquote>\n<div align=\"justify\">and Dr. Carroll commented:<\/div>\n<blockquote>\n<div align=\"justify\"><sup><strong><em>&quot;An FDA approval is the lowest bar possible, especially when nominal  statistical significance is valued over good clinimetric evidence. That  is what I have called the Cheshire cat effect &ndash; the only evidence that  the drug was there is a disembodied p value, grinning in statistical  space, with no connection to clinical reality.&quot;<\/em><\/strong><\/sup><\/div>\n<\/blockquote>\n<div align=\"justify\">We&#8217;re older and wiser now than we were in 2001, but I worry that with the famous <strong><font color=\"#200020\"><em>empty pipeline crisis<\/em><\/font><\/strong> that something like this might slide through on some <em><a target=\"_blank\" href=\"http:\/\/www.businessweek.com\/news\/2012-10-11\/fda-considers-faster-approval-process-for-obesity-drugs\"><u><strong><font color=\"#200020\">innovation gap<\/font><\/strong><\/u><\/a><\/em> fast track. Solanezumab <u>is<\/u> innovative. It just doesn&#8217;t happen to work! This one bears keeping up with&#8230;<\/div>\n","protected":false},"excerpt":{"rendered":"<p>I was scanning through older posts looking for something. I stopped on the one about Solanezumab for Alzheimer&#8217;s [SHOW ME THE DATA!&hellip;] and my eyes lingered on the titles of the two articles I&#8217;d listed: Eli Lilly surges on conflicting data for Alzheimer&rsquo;s drug solanezumab Experimental Lilly drug may help slow mental decline in people [&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":[2],"tags":[],"class_list":["post-28888","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/28888","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=28888"}],"version-history":[{"count":14,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/28888\/revisions"}],"predecessor-version":[{"id":28903,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/28888\/revisions\/28903"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=28888"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=28888"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=28888"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}