{"id":517,"date":"2014-07-05T16:39:00","date_gmt":"2014-07-05T16:39:00","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=517"},"modified":"2015-10-07T03:43:10","modified_gmt":"2015-10-07T07:43:10","slug":"bc-3781-passes-phase-2-with-flying-colors-readies-for-phase-3","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2014\/07\/05\/517\/bc-3781-passes-phase-2-with-flying-colors-readies-for-phase-3\/","title":{"rendered":"BC-3781 Passes Phase 2 with Flying Colors, Readies for Phase 3"},"content":{"rendered":"<p><a href=\"https:\/\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/07\/pleuromutilin1.jpe\"><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-full wp-image-519\" src=\"https:\/\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/07\/pleuromutilin1.jpe\" alt=\"pleuromutilin1\" width=\"176\" height=\"145\" \/><\/a>The pleuromutilins are a relatively \u2018old\u2019 class of antibiotics that have seen much use in veterinary but not in human medicine.\u00a0 According to EMA, Tiamulin is an \u201cessential antibiotic\u201d for the control of dysentery in pigs which is caused by Brachyspira hyodysenteriae, a macrolide-resistant pathogen.[1]\u00a0 Retapamulin \/ Altabax\u00ae was introduced by GSK into the clinic a few years ago; it is a topical antibiotic approved for the treatment of impetigo.\u00a0 A systemically absorbed pleuromutilin is as yet unavailable.<!--more--><\/p>\n<p>The pleuromutilin furthest advanced in development is BC-3781, a compound developed by Nabriva.\u00a0 Its Phase 2 program in ABSSSI was conducted between 2010-2012, with results published first in abstract form and then as a full publication by Prince and colleagues.[2]<\/p>\n<p>Because the drug class is unfamiliar to most clinicians, here a quick summary:<\/p>\n<ul>\n<li>The target of pleuromutilins\u00a0 is the 23 sRNA bacterial ribosome subunit; hence, the MoA is bacteriostatic<\/li>\n<li>The antimicrobial spectrum includes mainly Gram-positive bacteria, MRSA, PRSP, E. faecium (but not other enterococci), with MIC<sub style=\"color: #000000; font-style: normal;\">90<\/sub> in the 0.12 -0.5 \u00b5g\/mL range<\/li>\n<li>Activity against H. influenzae is adequate but MIC<sub>90<\/sub>s are 2-3 dilution steps lower than for S. aureus<\/li>\n<li>Excellent activity against M. pneumoniae, C. pneumophila, Legionella and M. catarrhalis<\/li>\n<li>activity against M. tuberculosis<\/li>\n<li>benign overall safety profile but some earlier compounds have shown liver toxicity in animal studies.<\/li>\n<\/ul>\n<p>Hence, BC-3781 should work very well for ABSSSI and CABP, in cases of atypical pneumonia and possibly as an agent for E. faecium.<\/p>\n<p>The paper by Prince [2] is of interest as it is the first large well-designed clinical trial of a systemic pleuromutilin in humans.\u00a0 Given the novelty of the compound class, we were curious about the safety \/ tolerability of BC-3781 in the 141 patients receiving either 100 or 150 mg PO q12h compared to vancomycin which was administered as 1g q12h.<\/p>\n<p>Most patients received treatment for 4-7 days.\u00a0 BC-3781 caused more infusion site reactions than the comparator, a finding already noticed in earlier Phase 1 dose-escalation trials.\u00a0 The frequency of GI related adverse events was low overall and not more than seen with vancomycin.\u00a0 Vancomycin, as would be expected, was associated with a higher incidence of pruritus. There was no signals pointing to any other system organ class (SOC), and LFTs were unremarkable.\u00a0 There were no deaths.\u00a0 Numbers of patients with severe AEs or prematurely discontinued were too small to draw conclusions.<\/p>\n<p>The authors mention QTc prolongation\u00a0 of 7, 11, and 12 msec in the vancomycin, BC-3781 100mg and BC-3781 150 mg dosing arms, respectively.\u00a0 These are relatively small changes that do not raise undue concerns but probably warrant monitoring in the next set of studies just to put the issue at rest.<\/p>\n<p>There is an oral intermediate release formulation of BC-3781 in development which would allow a convenient step-down treatment.\u00a0 For competitive reasons (oxazolidinones have a similar ribosomal MoA, bacterial spectrum, and list of indications), having a IV \/ PO pleuromutilin would be a big plus.<\/p>\n<p>Bottom line:\u00a0 With few new market entries expected in the coming years, a broad-spectrum drug like BC-3781 will have little competition and\u00a0high share of voice while addressing a significant medical need. \u00a0Not a bad place to be.<\/p>\n<hr \/>\n<p><strong>References:<\/strong><\/p>\n<p>[1] http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2012\/12\/WC500136418.pdf<\/p>\n<p>[2] Prince.\u00a0 Antimicrob Agents Chemother 2013; 57: 2087<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The pleuromutilins are a relatively \u2018old\u2019 class of antibiotics that have seen much use in veterinary but not in human medicine.\u00a0 According to EMA, Tiamulin is an \u201cessential antibiotic\u201d for the control of dysentery in pigs which is caused by Brachyspira hyodysenteriae, a macrolide-resistant pathogen.[1]\u00a0 Retapamulin \/ Altabax\u00ae was introduced <a class=\"more-link\" href=\"https:\/\/allphasepharma.com\/dir\/2014\/07\/05\/517\/bc-3781-passes-phase-2-with-flying-colors-readies-for-phase-3\/\">Continue reading <span class=\"screen-reader-text\">  BC-3781 Passes Phase 2 with Flying Colors, Readies for Phase 3<\/span><span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":859,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[19,227,18],"tags":[81,247,244,144,252,246,250,253,251,83,245,254,117,1371,222,249,9,248,48],"class_list":["post-517","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-qidp_antibiotic","category-recent_literature","category-the_viewpoint","tag-absssi","tag-altabax","tag-bc-3781","tag-broad-spectrum","tag-e-faecium","tag-gsk","tag-injection-site-reaction","tag-ivpo","tag-moa","tag-mrsa","tag-nabriva","tag-oxazolidinone","tag-pleuromutilin","tag-qidp","tag-qt-prolongation","tag-retapamulin","tag-safety","tag-tiamulin","tag-vancomycin"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/07\/QTnl-abnl.jpe","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-8l","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":1028,"url":"https:\/\/allphasepharma.com\/dir\/2014\/10\/05\/1028\/qidp-drugs-here-they-are-all-of-them\/","url_meta":{"origin":517,"position":0},"title":"QIDP Drugs: Here They Are, All of Them","author":"Harald","date":"October 5, 2014","format":false,"excerpt":"For the latest QIDP listing, please click HERE As of Oct. 9, 2014, there were by my accounting 30 compounds with QIDP designation. Here is the break-down: \u00a0 31 compounds with QIDP designation 29 antibacterials, 2 \u00a0antifungals 22 systemically active, 9\u00a0for topical administration 13 in Phase 3, 9 in Phase\u2026","rel":"","context":"In &quot;Did you know...?&quot;","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/10\/APPC-QIDP-copy.jpg?fit=640%2C200&ssl=1&resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/10\/APPC-QIDP-copy.jpg?fit=640%2C200&ssl=1&resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/10\/APPC-QIDP-copy.jpg?fit=640%2C200&ssl=1&resize=525%2C300 1.5x"},"classes":[]},{"id":2205,"url":"https:\/\/allphasepharma.com\/dir\/2015\/12\/23\/2205\/qidp-antibiotics-2015-year-end-update\/","url_meta":{"origin":517,"position":1},"title":"QIDP Antibiotics  &#8211;  2015 Year-End Update","author":"Harald","date":"December 23, 2015","format":false,"excerpt":"Here an updated listing of all QIDP drugs we are aware of as of 12\/24\/2015. Today just\u00a0facts and numbers; we will provide an interpretation of the current landscape in upcoming blogs. There are\u00a058 drugs which garnered QIDP status and these are listed in the Main Table below. With the recent\u2026","rel":"","context":"In &quot;QIDP Antibiotics&quot;","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/12\/QIDP-slider.jpg?fit=640%2C200&ssl=1&resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/12\/QIDP-slider.jpg?fit=640%2C200&ssl=1&resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/12\/QIDP-slider.jpg?fit=640%2C200&ssl=1&resize=525%2C300 1.5x"},"classes":[]},{"id":561,"url":"https:\/\/allphasepharma.com\/dir\/2014\/07\/10\/561\/the-difficult-transition-into-phase-3\/","url_meta":{"origin":517,"position":2},"title":"The Difficult Transition Into Phase 3","author":"Harald","date":"July 10, 2014","format":false,"excerpt":"Preclinical and early clinical development is expensive enough already for VC companies but it gets really expensive in Phase 3.\u00a0 Hence, not surprisingly, few small companies tackle Phase 3 programs on their own.\u00a0 Unless an 'angel investor' with deep pockets commits to the compound and assures continuity of development, the\u2026","rel":"","context":"In &quot;The Viewpoint&quot;","block_context":{"text":"The Viewpoint","link":"https:\/\/allphasepharma.com\/dir\/category\/the_viewpoint\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/07\/DrugDevProcess.jpg?fit=640%2C200&ssl=1&resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/07\/DrugDevProcess.jpg?fit=640%2C200&ssl=1&resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/07\/DrugDevProcess.jpg?fit=640%2C200&ssl=1&resize=525%2C300 1.5x"},"classes":[]},{"id":1800,"url":"https:\/\/allphasepharma.com\/dir\/2015\/08\/01\/1800\/qidp-drugs-4th-edition\/","url_meta":{"origin":517,"position":3},"title":"QIDP Drugs &#8211;  4th Edition","author":"Harald","date":"August 1, 2015","format":false,"excerpt":">>> For the latest QIDP list, please click HERE \u00a0<<< Since our\u00a0last QIDP blog from April 8, 2015, several new drugs have made the list which now includes 41 compounds. Below a table\u00a0which includes compound, sponsor\u00a0and development stage (Phase). It also indicates whether a drug has been\u00a0the topic of a\u2026","rel":"","context":"In &quot;Recent Literature&quot;","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"QIDP 4th edition","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/08\/QIDP-4th-edition.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/08\/QIDP-4th-edition.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/08\/QIDP-4th-edition.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2911,"url":"https:\/\/allphasepharma.com\/dir\/2016\/11\/25\/2911\/prospecting-antibiotics\/","url_meta":{"origin":517,"position":4},"title":"Prospecting for New Antibiotics","author":"Harald","date":"November 25, 2016","format":false,"excerpt":"The QIDP designation was introduced in 2012 to incentivize drug development in antiinfectives. QIDP came with several attractive features, such as prolongation of patent life, FDA\u00a0expedited review and more.\u00a0 In addition, FDA made it quite easy to garner the label.\u00a0 As you can see, there is really no downside to\u2026","rel":"","context":"In &quot;Did you know...?&quot;","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"engine-qidp-blog","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/11\/Engine-QIDP-blog.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/11\/Engine-QIDP-blog.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/11\/Engine-QIDP-blog.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2817,"url":"https:\/\/allphasepharma.com\/dir\/2016\/10\/24\/2817\/qidp-drug-update-part-2-categories-of-interest\/","url_meta":{"origin":517,"position":5},"title":"QIDP Drug Update \u2013 Part 2: \u00a0Categories of Interest","author":"Harald","date":"October 24, 2016","format":false,"excerpt":"According to Janet Woodcock, 63 drugs have been given the \u201cQIDP\u201d designation so far. Our inofficial list has 61 drugs, of which we believe only 57 are still in active clinical development.\u00a0 So we are in fairly close agreement. That may seem like an impressive record but it is also\u2026","rel":"","context":"In &quot;QIDP Antibiotics&quot;","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"qidp-part2-slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/QIDP-Part2-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/QIDP-Part2-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/QIDP-Part2-slider.jpg?resize=525%2C300 1.5x"},"classes":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/517","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/comments?post=517"}],"version-history":[{"count":4,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/517\/revisions"}],"predecessor-version":[{"id":2017,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/517\/revisions\/2017"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media\/859"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=517"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=517"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=517"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}