{"id":64392,"date":"2016-04-02T13:36:56","date_gmt":"2016-04-02T17:36:56","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=64392"},"modified":"2016-04-03T02:22:55","modified_gmt":"2016-04-03T06:22:55","slug":"a-pipeline-rejig","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/04\/02\/a-pipeline-rejig\/","title":{"rendered":"a pipeline rejig&#8230;"},"content":{"rendered":"<div align=\"justify\" class=\"small\">In the course of reading about the FDA&#8217;s rejection of <font color=\"#200020\">Lundbeck\/Takeda<\/font>&#8216;s bid for a <font color=\"#200020\">Cognitive Dysfunction in MDD<\/font> for <font color=\"#200020\">Brintellix&reg; [<\/font><font color=\"#200020\"><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2016\/03\/30\/still-going-strong\/\">still going strong?&hellip;<\/a>],<\/font><font color=\"#200020\"> I ran across <\/font>another article in <strong><font color=\"#000001\">Fierce<\/font><font color=\"#ff0000\">Pharma<\/font><\/strong>, the one that got me thinking about the <em><font color=\"#200020\">pipeline<\/font><\/em> in general [<a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2016\/03\/31\/the-pipeline-paradigm\/\">the pipeline paradigm&hellip;<\/a>]. It&#8217;s about another <font color=\"#200020\">Lundbeck<\/font> drug &#8211; an Atypical Antipsychotic [Lu AF35700] &#8211; note the date. If I read this right, they&#8217;ve completed three Phase 1 Clinical Trials,     <\/div>\n<ul><sup>      <\/p>\n<li>\n<div align=\"justify\"><strong><font color=\"#990000\">completed<\/font><\/strong> <a href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02333487?term=Lu+AF35700&#038;rank=1&#038;submit_fld_opt=\" target=\"__blank\">Positron  Emission Tomography (PET) Study Investigating Dopamine and Serotonin  Receptor Occupancy After Multiple Oral Dosing of Lu AF35700<\/a> [22 subjects]<\/div>\n<\/li>\n<li>\n<div align=\"justify\"><strong><font color=\"#990000\">completed<\/font><\/strong> <a href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02093169?term=Lu+AF35700&#038;rank=2&#038;submit_fld_opt=\" target=\"__blank\">D2 Dopamine Receptor Occupancy After Oral Dosing of Lu AF35700 in Healthy Men Using [11C]-PHNO as Tracer Compound<\/a> [12 subjects]<\/div>\n<\/li>\n<li>\n<div align=\"justify\"><strong><font color=\"#990000\">completed<\/font><\/strong> <a href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02202226?term=Lu+AF35700&#038;rank=3&#038;submit_fld_opt=\" target=\"__blank\">Safety and Tolerability Study of Lu AF35700 After Repeated Dosing in Patients With Schizophrenia<\/a> [96 subjects]<\/div>\n<\/li>\n<p>     <\/sup><\/ul>\n<div align=\"justify\" class=\"small\">been granted <a href=\"http:\/\/www.fda.gov\/ForPatients\/Approvals\/Fast\/ucm405399.htm\" target=\"_blank\"><font color=\"#200020\">Fast-Track<\/font><\/a> status by the FDA [November 2015], and are off and running with a Phase III Clinical Trial,<\/div>\n<ul><sup>      <\/p>\n<li>\n<div align=\"justify\"><strong><font color=\"#009900\">recruiting<\/font><\/strong> <a href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02717195?term=Lu+AF35700&#038;rank=4&#038;submit_fld_opt=\" title=\"Show study NCT02717195: Effect of Lu AF35700 in Patients With Treatment-resistant Schizophrenia\">Effect of Lu AF35700 in Patients With Treatment-resistant Schizophrenia<\/a> [964 subjects]<\/div>\n<\/li>\n<p>       <\/sup><\/ul>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/www.fiercebiotech.com\/story\/lundbecks-big-bet-schizophrenia-kicks-1000-person-phiii-trial\/2016-03-17\" target=\"_blank\">Lundbeck&#8217;s big bet on schizophrenia kicks off with 1,000-person PhIII trial<\/a><\/div>\n<div align=\"center\" class=\"big\"><strong><font color=\"#000001\">Fierce<\/font><font color=\"#ff0000\">Pharma<\/font><\/strong><\/div>\n<div align=\"center\" class=\"middle\">By Nick Paul Taylor<\/div>\n<div align=\"center\" class=\"middle\">March 17, 2016<\/div>\n<div align=\"center\" class=\"small\">[<a target=\"_blank\" href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02717195\">NCT02717195<\/a>]<\/div>\n<p align=\"justify\">Lundbeck  has started the first of several planned Phase III trials of its  candidate against treatment-resistant schizophrenia, Lu AF35700. The  candidate is a key component of the turnaround strategy initiated by  K&aring;re Schultz, <em><strong><font color=\"#660033\">who has shed other pipeline prospects in order to up  Lundbeck&#8217;s bet on Lu AF35700 since taking over as CEO last year.<\/font><\/strong><\/em><\/p>\n<p align=\"justify\">Copenhagen, Denmark-based Lundbeck is kicking off the pivotal trial  program of the experimental drug with a Phase III study that will  recruit 1,000 patients across 15 countries. In the study, Lundbeck will  administer one of two doses of Lu AF35700 to patients with  treatment-resistant schizophrenia. If the drug works as Lundbeck hopes,  participants&#8217; scores on the Positive and Negative Syndrome Scale [PANSS]  will improve following 10 weeks of treatment. The primary PANSS  endpoint is being supplemented with Clinical Global Impression &ndash;  Severity of Illness scores and Personal and Social Performance Scale  data.<\/p>\n<p align=\"justify\">Lundbeck expects to be running the study for the next three years,  during which time it will roll out additional trials with a view to  gathering data on more than 2,000 people with treatment-resistant  schizophrenia. The size of the bet is proportional to Lundbeck&#8217;s  assessment of the scale of the unmet need and opportunity associated  with treatment-resistant schizophrenia. &quot;Today there is only one therapy  approved for patients with treatment-resistant schizophrenia, and its  use is severely limited by its problematic safety profile,&quot; Lundbeck  R&amp;D Chief Anders Gersel Pedersen said in a statement&#8230;<\/p>\n<\/blockquote>\n<div align=\"justify\" class=\"small\">The drug they&#8217;re looking to compete with is <font color=\"#200020\">Clozaril<\/font>, based on the fact that <a href=\"https:\/\/globenewswire.com\/news-release\/2016\/03\/11\/819027\/0\/en\/Lundbeck-starts-clinical-phase-III-program-with-Lu-AF35700-in-patients-with-treatment-resistant-schizophrenia.html\" target=\"_blank\">Lu AF35700<\/a> has a strong D1 receptor binding like <font color=\"#200020\">Clozaril<\/font>, but a weaker D2 binding. Surely I&#8217;ve missed something here because the only study I see in Schizophrenia is the 3 week safety <a target=\"_blank\" href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02202226?term=Lu+AF35700&#038;rank=3&#038;submit_fld_opt=\">study<\/a> &#8211; nothing that even determines that the drug has antipsychotic properties that I could find [?]:   <\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a target=\"_blank\" href=\"http:\/\/www.fiercebiotech.com\/story\/lundbeck-advance-schizophrenia-drug-solo-after-taking-ax-early-stage-pipeli\/2015-08-20?utm_medium=rss&#038;utm_source=feedly&#038;utm_campaign=rss\">Lundbeck to advance schizophrenia drug solo after taking an ax to early-stage pipeline<\/a><\/div>\n<div align=\"center\" class=\"big\"><strong><font color=\"#000001\">Fierce<\/font><font color=\"#ff0000\">Pharma<\/font><\/strong><\/div>\n<div align=\"center\" class=\"middle\">By Nick Paul Taylor<\/div>\n<div align=\"center\" class=\"middle\">August 20, 2015<\/div>\n<p align=\"justify\"><strong><font color=\"#660033\">Lundbeck&nbsp; has initiated a rejig of its pipeline, taking an ax to undisclosed  early-stage assets in order to funnel cash into what it sees as its most  promising candidates. The schizophrenia drug Lu AF35700 is among the  beneficiaries of the reshuffle, with Lundbeck using its reorganized  balance sheet to advance the therapy through development unpartnered.<\/font><\/strong><\/p>\n<p align=\"justify\">Copenhagen, Denmark-based Lundbeck unveiled the tweaks to its R&amp;D  priorities alongside sweeping changes to its operations, which will see  it shed 1,000 jobs in an attempt to become profitable. The commercial  operation is expected to bear the brunt of the cuts but R&amp;D will be  affected, too, with recently-appointed CEO K&aring;re Schultz committing to  dropping certain early-stage assets. Trimming the pipeline will allow  Lundbeck top focus its cash on programs in which it thinks it has the  clearest understanding of the underlying science, such as the  schizophrenia drug Lu Af35700.<\/p>\n<div align=\"justify\"><em><strong><font color=\"#660033\">&quot;35700 is an antipsychotic with a profile that is somewhat different  than most drugs available. What we see is that many of the drugs that  are available on the market today are predominantly driving effects  through D2,&quot; Lundbeck R&amp;D chief Anders Gersel Pedersen said on a  conference call. 35700, like clozapine, has a strong binding affinity to  the D1 receptor. Lundbeck hopes to differentiate its pipeline candidate  from clozapine through its side effect profile, giving patients who are  resistant to D2-targeted drugs a treatment option that doesn&#8217;t cause  weight gain and metabolic disturbances. Lundbeck&#8217;s belief in this hypothesis has led it to conclude Lu  Af35700 is among its most promising early-stage assets. &quot;We have to put  our bets where we think we have the best ability to translate science  into products,&quot; Pederson said&#8230;<\/font><\/strong><\/em><\/div>\n<\/blockquote>\n<div align=\"justify\" class=\"small\">While this post is a little bit about Lu AF35700, I&#8217;ll have to admit it&#8217;s also about something else. When the announcement that the FDA had turned down that sNDA for <font color=\"#200020\">Brintellix&reg;<\/font>, I was intrigued by the number of sites Google found echo-ing the announcement. They were mostly business\/investor sites and they had a surprising amount of sophisticated science thrown in. I started looking at what else was on those sites, and was frankly amazed. I&#8217;ve spent the last several days bouncing from place to place in that domain that was, for me, new territory. One thing I learned was that if you want to know about what&#8217;s in the pipeline and what&#8217;s up with clinical trials, that&#8217;s the place to look &#8211; not in the medical universe [unless you consider that the medical universe].<\/div>\n<p> <\/p>\n<div align=\"justify\" class=\"small\">A lot of the material on the investor sites came from press releases by the various PHARMA companies, and so they were generally upbeat, like this one for <a href=\"https:\/\/globenewswire.com\/news-release\/2016\/03\/11\/819027\/0\/en\/Lundbeck-starts-clinical-phase-III-program-with-Lu-AF35700-in-patients-with-treatment-resistant-schizophrenia.html\" target=\"_blank\">Lu AF35700<\/a>. I had a few laughs thinking that the investment world was in the same boat we&#8217;re in, a target for spin, and in real need of some <em><font color=\"#200020\">Data Transparency<\/font><\/em> too. But there were some other things &#8211; like <a target=\"_blank\" href=\"http:\/\/www.fiercepharma.com\/story\/surprise-decision-fda-blocks-crucial-cognitive-claim-takedas-brintellix\/2016-03-29\">this quote<\/a> about the <font color=\"#200020\">Brintellix&reg;<\/font> ruling:<\/div>\n<blockquote>\n<div align=\"justify\">The FDA  doesn&rsquo;t have to follow the advice of its expert review panels,  but it  usually does. That&rsquo;s a standard line in stories about advisory  committee  votes. Unfortunately for Lundbeck and Takeda, their new <font color=\"#200020\">Brintellix<\/font> app is <em><strong><font color=\"#660033\">one of the unlucky ones<\/font><\/strong><\/em>.<\/div>\n<\/blockquote>\n<div align=\"justify\" class=\"small\"><img decoding=\"async\" border=\"1\" align=\"right\" width=\"176\" hspace=\"4\" src=\"http:\/\/1boringoldman.com\/images\/seventh-seal-2.jpg\" \/>I doubt most of us would say it that way [&quot;<em><strong><font color=\"#660033\">unlucky<\/font><\/strong><\/em>&quot;]. There was a surprising-to-me absence of attention to the actual medical benefit or risk &#8211; mainly comments on success or failure of various gambits. I&#8217;m not being hyper-moral here, business sites are about business after all. It was just a bit jarring &#8211; as was something else. Much of this literature is about strategies. It reads like a huge chess game with the various moves and gambits cataloged, and sometimes relished. In the case of Lu AF35700, Lundbeck&#8217;s new CEO, K&aring;re Schultz,&nbsp; is shutting down some of Lundbeck&#8217;s R&amp;D, laying off employees, and dropping other candidate drugs to raise the cash for his big bet on Lu AF35700 [AKA rejig]. A 1000 Subject three year International Clinical Trial is apparently going to cost them a mint. Just like the failed bet they made on <font color=\"#200020\">Brintellix&reg;<\/font> to be a <em><font color=\"#200020\">think-better<\/font><\/em> antidepressant cost them dearly. It&#8217;s little surprise they hauled in the uber-KOLs for that FDA hearing. <\/div>\n<p align=\"justify\" class=\"small\">I hadn&#8217;t thought of it before, and maybe it was <strong><font color=\"#200020\">The Big Short<\/font><\/strong> movie that had me in this frame of mind, but a lot of the investing in pharmaceuticals is analogous to the Commodities Market &#8211; betting on a future value. Again, the <em><font color=\"#200020\">pipeline paradigm<\/font><\/em>, as in being in a position to reap large profits when and if the product flows out into the market. I suppose any business venture is like that, but here, it&#8217;s in bas relief because of the long development process, the FDA&#8217;s yes\/no position, the guaranteed time limited monopoly afforded by the patent\/exclusivity laws, and the presence of those pesky middlemen [AKA physicians]. So if Lu AF35700 turns out as they hope [a non-toxic Clozaril], as things now stand, they&#8217;ll be able to charge Gilead\/Valeant\/Shkreli prices &#8211; the treatment-resistant Schizophrenia patients are unlikely to have very deep pockets, so  I presume they&#8217;re aiming at third patry payers.<\/p>\n<div align=\"justify\" class=\"small\">There&#8217;s plenty more to say about the Lu AF35700 study itself, but it&#8217;s for another day. I just wanted to report on my visit to other side&#8230; <\/div>\n","protected":false},"excerpt":{"rendered":"<p>In the course of reading about the FDA&#8217;s rejection of Lundbeck\/Takeda&#8216;s bid for a Cognitive Dysfunction in MDD for Brintellix&reg; [still going strong?&hellip;], I ran across another article in FiercePharma, the one that got me thinking about the pipeline in general [the pipeline paradigm&hellip;]. It&#8217;s about another Lundbeck drug &#8211; an Atypical Antipsychotic [Lu AF35700] [&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-64392","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/64392","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=64392"}],"version-history":[{"count":24,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/64392\/revisions"}],"predecessor-version":[{"id":64416,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/64392\/revisions\/64416"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=64392"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=64392"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=64392"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}