{"id":2142,"date":"2015-11-23T01:34:15","date_gmt":"2015-11-23T06:34:15","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=2142"},"modified":"2016-03-23T04:39:09","modified_gmt":"2016-03-23T08:39:09","slug":"eravacycline-conference-call-unrevealing-and-disappointing","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/11\/23\/2142\/eravacycline-conference-call-unrevealing-and-disappointing\/","title":{"rendered":"Eravacycline Conference Call: Unrevealing and Disappointing"},"content":{"rendered":"<p><a href=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/Watertown-copy.jpg?ssl=1\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-2143 aligncenter\" src=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/Watertown-copy.jpg?resize=530%2C232&#038;ssl=1\" alt=\"Watertown copy\" width=\"530\" height=\"232\" srcset=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/Watertown-copy.jpg?w=640&amp;ssl=1 640w, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/Watertown-copy.jpg?resize=300%2C131&amp;ssl=1 300w\" sizes=\"auto, (max-width: 530px) 100vw, 530px\" \/><\/a><\/p>\n<p>Whatever has become of investigative journalism?\u00a0 All we read after the Stifel conference call (11\/17\/2015) is descriptive rehash of information provided by Tetraphase at the conference.\u00a0 No probing questions that we thought investors would ask who just lost 80% of their money.\u00a0 No signs of analytical or strategic readjustment at Tetraphase in response to the new reality which is just this: We\u00a0don\u2019t have an oral eravacycline formulation any more!<\/p>\n<p>There goes the prospect of any IV\/PO sequential therapy, a sine-qua-non in a competitive market, and the analysts don\u2019t bat an eyelid.\u00a0 The investor community was told that the company wants to start a new cUTI study by mid-2016, this time as a purely IV treatment without PO step-down.\u00a0 This is a solution to satisfy the regulators and get you to an NDA, but it will not make eravacycline successful\u00a0in the market place. \u00a0With this approach all prospects of becoming a competitive player in the large and lucrative cUTI arena are now dismal. \u00a0 <div class=\"simplePullQuote right\"><p><span style=\"color: #800000\"><em>There goes the prospect of any IV\/PO sequential therapy, a sine-qua-non in a competitive market, and the analysts don\u2019t bat an eyelid<\/em><\/span><\/p>\n<\/div><\/p>\n<p>The company tells us that they will be submitting more data to FDA in the hopes of getting the current program approved without further clinical data.\u00a0 In other words, Tetraphase would like to find ways to have eravacycline approved for complicated intra-abdominal infection (cIAI) as a single indication with a single pivotal trial (IGNITE-1).\u00a0 Fat chance!<\/p>\n<p>There are now several hits that affect the revenue potential for eravacycline, and none were adequately discussed:<\/p>\n<ul>\n<li>The duration of clinical development will be 2 years longer at least (assuming no new surprises!)\n<ul>\n<li>this time will be needed for execution of the new cUTI trial<\/li>\n<li>the opportunity cost for this delay is immense (USD 500-750 mio)<\/li>\n<\/ul>\n<\/li>\n<li>The profit potential is severely reduced by the absence of IV\/PO sequential therapy\n<ul>\n<li>this makes eravacycline much less competitive in cUTI, ABSSSI, CAP or any other f\/u indication they choose to pursue<\/li>\n<\/ul>\n<\/li>\n<li>The additional costs of studies to produce a submission dossier:\n<ul>\n<li>the cost of a new cUTI study was quoted as USD 25-30 mio (not sure whether their quote includes internal costs)<\/li>\n<li>the additional work required to explain the failure of IGNITE-2<\/li>\n<li>any new formulation work to come up with a bioequivalent PO formulation<\/li>\n<\/ul>\n<\/li>\n<li>The loss of a competitive advantage over omadacycline:\n<ul>\n<li>After eravacycline nicely surpassed omadacycline in development, the 2 programs are now much closer together again<\/li>\n<li>If omadacycline\u2019s PO formulation holds up in clinical trials, then it has a much better chance to become the predominant player<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>We would have expected to hear about the PK profile of the IV vs the PO formulation in the cUTI trial, or about the tests that the company has done to show bioequivalence. \u00a0Why were both 200 and 250 mg PO doses considered \u201cbioequivalent?\u00a0 \u00a0Both could not possibly be bioequivalent to the 1.5 mg\/kg IV, even the higher 250 mg dose is borderline low for anyone but cachectic adults. How did body weight correlate with outcomes, both clinical and bacteriological? What about the urinary levels achieved with eravacycline IV and PO in IGNITE-2?\u00a0 Were there any particular microbes which were inadequately covered in IGNITE-2?\u00a0 We were provided with no\u00a0answers.<\/p>\n<p>There is a need to understand why the PO formulation failed, and\/or why PK\/PD modeling got it wrong. \u00a0The company ought to share their\u00a0learnings with the development community at large. \u00a0Call it fault analysis or something else, just telling us that the PO formulation dragged down the\u00a0efficacy seen with IV is not enough explanation.<\/p>\n<p>This company needs a wake-up call from some activist investors; Tetraphase seems to have a very benevolent supervisory group. \u00a0Management is sitting cozily on their USD 223 mio, which will be melting away soon enough.\u00a0 Their plan to stick with the original goal and handle the Phase 3 program without a partner stands on hollow foundations these days, we are afraid.<\/p>\n<p>Someone has moved their cheese, but they may haven\u2019t noticed yet, or perhaps it is a case of the emperor having no clothes. \u00a0What do you think?<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Whatever has become of investigative journalism?\u00a0 All we read after the Stifel conference call (11\/17\/2015) is descriptive rehash of information provided by Tetraphase at the conference.\u00a0 No probing questions that we thought investors would ask who just lost 80% of their money.\u00a0 No signs of analytical or strategic readjustment at <a class=\"more-link\" href=\"https:\/\/allphasepharma.com\/dir\/2015\/11\/23\/2142\/eravacycline-conference-call-unrevealing-and-disappointing\/\">Continue reading <span class=\"screen-reader-text\">  Eravacycline Conference Call: Unrevealing and Disappointing<\/span><span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":2143,"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":[19,3,18],"tags":[1271,403,1434,354,355,428,425,5,1583,1437,1331,1438,1436,969,433,1435,39,437,435],"class_list":["post-2142","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-qidp_antibiotic","category-the_news","category-the_viewpoint","tag-allphase-pharma-consulting","tag-antibiotic-blog","tag-bioequivalent-doses","tag-ciai","tag-cuti","tag-dose-finding","tag-eravacycline","tag-fda","tag-harald-reinhart","tag-ignite-1","tag-ignite-2","tag-intra-abdominal-infection","tag-microbiology","tag-nda","tag-omadacycline","tag-pk-profile","tag-pkpd","tag-step-down-therapy","tag-tetraphase"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/Watertown-copy.jpg?fit=640%2C280&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-yy","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":1958,"url":"https:\/\/allphasepharma.com\/dir\/2015\/09\/24\/1958\/after-icaac-some-more-thoughts-on-eravacycline-in-cuti-and-ignite-2\/","url_meta":{"origin":2142,"position":0},"title":"After ICAAC: Some More Thoughts on Eravacycline in cUTI and IGNITE-2","author":"Harald","date":"September 24, 2015","format":false,"excerpt":"When a well-designed pivotal Phase 3 trial fails to show NI, it demands an explanation.\u00a0 While awaiting the company\u2019s analysis of the data, many possible explanations are bandied about.\u00a0 So it was not surprising that the eravacycline cUTI study (IGNITE-2) was mentioned quite often during ICAAC 2015, in sessions and\u2026","rel":"","context":"In &quot;QIDP Antibiotics&quot;","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"Erava2blog copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=525%2C300 1.5x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=700%2C400 2x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=1050%2C600 3x"},"classes":[]},{"id":689,"url":"https:\/\/allphasepharma.com\/dir\/2014\/08\/04\/689\/some-thoughts-about-eravacycline-based-on-the-phase-2-ciai-study\/","url_meta":{"origin":2142,"position":1},"title":"Some Thoughts about Eravacycline Based on the Phase 2 cIAI Study","author":"Harald","date":"August 4, 2014","format":false,"excerpt":"Solomkin et al. conclude that the efficacy and safety of eravacycline compares favorably to the control drug, ertapenem.[1]\u00a0 This top-level assessment is made with the usual caveats (insufficient statistical power, small sample size), but a few points deserve comment. Eravacycline is a fluorocycline; as a tetracycline derivative it follows into\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\/2014\/08\/eravacycline-copy.jpg?fit=481%2C212&ssl=1&resize=350%2C200","width":350,"height":200},"classes":[]},{"id":2697,"url":"https:\/\/allphasepharma.com\/dir\/2016\/09\/19\/2697\/timely-new-information-on-next-generation-tetracyclines-part-2-eravacycline-and-protein-binding\/","url_meta":{"origin":2142,"position":2},"title":"Timely New Information on Next-Generation Tetracyclines \u2013 Part 2: Eravacycline and Protein Binding","author":"Harald","date":"September 19, 2016","format":false,"excerpt":"A recent paper by Thabit describes a curious finding [1]. The authors measured total and free (i.e.,\u00a0nonprotein-bound) eravacycline levels at ascending doses in a mouse model. They found strikingly small increases in free drug levels when titrating up\u00a0total doses. The effect was rather dramatic: an increase in\u00a0protein binding from 12%\u2026","rel":"","context":"In &quot;QIDP Antibiotics&quot;","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"Horserace Tigecycline Erava","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/09\/Horserace-Tigecycline-Erava.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/09\/Horserace-Tigecycline-Erava.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/09\/Horserace-Tigecycline-Erava.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2676,"url":"https:\/\/allphasepharma.com\/dir\/2016\/09\/13\/2676\/timely-new-information-on-next-generation-tetracyclines-part-1-omadacycline-and-cardiac-aes\/","url_meta":{"origin":2142,"position":3},"title":"Timely New Information on Next-Generation Tetracyclines \u2013 Part 1: Omadacycline and Cardiac AEs","author":"Harald","date":"September 13, 2016","format":false,"excerpt":"Several\u00a0interesting articles appeared recently which shed light on the efficacy of eravacycline and the safety of\u00a0omadacycline, both in Phase 3 and both in a head-to-head race to the market.\u00a0 Well, the term \u2018race\u2019 is bit of a stretch as both drugs have seen very significant delays in development. Omadacycline from\u2026","rel":"","context":"In &quot;QIDP Antibiotics&quot;","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"Horserace Tigecycline Omada","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/08\/Horserace-Tigecycline-Omada.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/08\/Horserace-Tigecycline-Omada.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/08\/Horserace-Tigecycline-Omada.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":3144,"url":"https:\/\/allphasepharma.com\/dir\/2017\/02\/09\/3144\/smiles-press-conference-plazomicin-delivers\/","url_meta":{"origin":2142,"position":4},"title":"All Smiles at the Press Conference: Plazo+Levo Delivers","author":"Harald","date":"February 9, 2017","format":false,"excerpt":"This December, Achaogen released much data on 2 plazomicin trials[1]: the pivotal EPIC study comparing plazomicin \/ levofloxacin with meropenem\u00a0\/ levofloxacin in cUTI is the one we want to look at today because it is interpretable, while the other trial called CARE is not. CARE is one of those observational\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\/2017\/02\/Plazomicin-sldier.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/02\/Plazomicin-sldier.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/02\/Plazomicin-sldier.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1168,"url":"https:\/\/allphasepharma.com\/dir\/2014\/12\/15\/1168\/the-circuitous-route-to-phase-3-another-chapter-in-the-fitful-development-of-ptk-0796\/","url_meta":{"origin":2142,"position":5},"title":"The Circuitous Route to Phase 3:\u00a0 Another Chapter in the Fitful Development of PTK-0796","author":"Harald","date":"December 15, 2014","format":false,"excerpt":"When antibiotics change hands, it can be a good thing.\u00a0 Small companies are often desperate to attract a partner with \u2018deep pockets\u2019 to help them finance an expensive late phase development but often have to give up control once\u00a0the honeymoon period is over.\u00a0 Such transitions can bring delays because new\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\/2014\/12\/PTK-slider-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\/12\/PTK-slider-copy.jpg?fit=640%2C200&ssl=1&resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/12\/PTK-slider-copy.jpg?fit=640%2C200&ssl=1&resize=525%2C300 1.5x"},"classes":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2142","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=2142"}],"version-history":[{"count":8,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2142\/revisions"}],"predecessor-version":[{"id":2155,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2142\/revisions\/2155"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media\/2143"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=2142"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=2142"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=2142"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}