{"id":1769,"date":"2015-07-28T01:45:31","date_gmt":"2015-07-28T05:45:31","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=1769"},"modified":"2015-12-30T12:58:24","modified_gmt":"2015-12-30T17:58:24","slug":"the-demise-of-kb001-part-2-an-anti-pseudomonas-antibody-hits-the-dust-instead-of-paydirt","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/07\/28\/1769\/the-demise-of-kb001-part-2-an-anti-pseudomonas-antibody-hits-the-dust-instead-of-paydirt\/","title":{"rendered":"The Demise of KB001 (Part 2): An Anti-Pseudomonas Antibody Hits the Dust (instead of Paydirt)"},"content":{"rendered":"

F\"KB<\/a>OR\u00a0PART 1, CLICK HERE<\/a><\/p>\n

Should we assume that the results of this Global Epi Study were the reason why Sanofi became disillusioned about the prospects of KB001? \u00a0Or was it an internal strategic decision based on portfolio-review where KB001 just no longer made the cut?<\/p>\n

The results of the Global Epi Study are published and deserve a closer look.[1]<\/a><\/p>\n

This was a truly impressive surveillance study of the risk for\u00a0VAP in intubated patients.\u00a0 It involved 1853 patients from 56 centers on 4 continents. \u00a0Quite uniformly, VAP occurred in 16% of intubated patients, with P.aeruginosa being the most frequently isolated pathogen in 4.1% (or 26% in relative terms), and S. aureus coming in as a close second.<\/p>\n

Not surprisingly, prior colonization with P. aeruginosa increased the likelihood of developing P. aeruginosa VAP (PAVAP) by a factor of 8. \u00a0Unfortunately, such predictive surveillance cultures \u2013 either as TAs or mini-BALs – are rarely\u00a0done in clinical practice. So it must have come as a disappointment to the sponsor that other more specific risk factors for PAVAP could not be identified.\u00a0 When only 1 of 25 ventilated ICU patients develops P. aeruginosa pneumonia, an intervention reducing the incidence of PAVAP would\u00a0be a difficult undertaking.

The business case was probably too borderline for Sanofi to continue the alliance<\/span><\/p>\n<\/div><\/p>\n

Without a diagnostic tool to hone in on the target population of patients colonized with P. aeruginosa, Sanofi probably felt that there was no workable commercial model to make KB001 a success.\u00a0 Or that the business case was too borderline.\u00a0 We believe this was the main driver for their decision to abandon the KB001 alliance.<\/p>\n

Changes in clinical practice that occurred while the Global Epi Study was underway may have contributed, making a “VAP prevention” program less attractive for Sanofi:<\/p>\n

    \n
  1. CMS changed its reimbursement for VAP considering it a nosocomial preventable disease. This fact alone reduced the reported incidence figures for VAP in US hospitals substantially;<\/li>\n
  2. True improvements in patient care brought about by the introduction of\u00a0the\u00a0\u201cVAP bundle\u201d.\u00a0 Numerous publications attest to the fact that intubated patients managed accordingly are\u00a0less likely to develop VAP\u00a0[2]<\/a>.<\/li>\n<\/ol>\n

    It should also be mentioned that almost all intubated patients receive broad-spectrum antibiotic prophylaxis (for selective decontamination) despite ATS Guidelines recommending a more differentiated approach\u00a0[3]<\/a>.\u00a0 So, with fewer cases of VAP around and no good markers to select patients at high risk for PAVAP, Sanofi probably felt this would be a difficult, risky, costly, and not very profitable program to continue.<\/p>\n

    Arguably, Sanofi could have turned\u00a0the Global Epi Study into a pivotal Phase 3 study

    You could say:<\/span>
    \n<\/em><\/strong>778 patients are required to have a 80% chance of detecting, as significant at the 5% level, a decrease in the primary outcome measure from 24% in the control group to 16% in the experimental group<\/span><\/p>\n<\/div>by adding\u00a0a blinded KB001-A intervention arm.\u00a0 Indeed, demonstrating\u00a0superiority would not seem all that\u00a0difficult when\u00a0you crunch the numbers: \u00a0Assuming a 33% superiority over placebo, 80% power, alpha = 0.05, and a PAVAP incidence of 20-25%, one would need to enroll approx. 800 VAP patients in a 2-arm study.\u00a0 Expensive?\u00a0 Not really.\u00a0 Feasible?\u00a0 Yes.\u00a0 Not for the faint of heart, of course, but doable.\u00a0 A project attractive for Big Pharma? \u00a0A difficult sell.<\/p>\n

    Certainly Sanofi had bigger fish to fry – \u00a0like the new cholesterol drug which just got approved\u00a0[4]<\/a>.\u00a0 So, our educated guess is that KB001 fell victim to\u00a0a reshuffling of priorities at a portfolio review for all the reasons mentioned above. \u00a0Hey, nothing personal!<\/p>\n

    Others companies are still pursuing the TTSS target, as they should.\u00a0 Let\u2019s see how the compounds from Microbiotix, Shionogi and \u00a0MedImmune (MEDI-3902) fare in PAVAP prevention trials[5]<\/a>.<\/p>\n

    \"KB<\/a><\/p>\n

    Update on Kalobios: \u00a0The company filed for bankruptcy Dec. 30, 2015.<\/p>\n

     <\/p>\n

    Abbreviations:<\/strong>
    \nPAVAP \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 P. aeruginosa VAP
    \nVAP \/ VABP \u00a0 ventilator-associated (bacterial) pneumonia
    \nRIP \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 requiescat in pace
    \nTA \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 tracheal aspirate
    \nBAL \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0broncho-alveolar lavage
    \nCMS \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 Centers for Medicare &\u00a0Medicaid Services<\/p>\n

    References:
    \n<\/strong>    [1]<\/a> M Kollef\u00a0 Crit Care Med 42: 2178, 2014
    \n    [2]<\/a> G Bassi Semin Respir Crit Care Med. 2014;35:469
    \n    [3]<\/a> ATS\/IDSA Guideline Committee.\u00a0 Am J Respir Crit Care Med Vol 171. pp 388\u2013416, 2005\u00a0 Note: A new Guideline is currently being developed
    \n    [4]<\/a> http:\/\/www.nytimes.com\/2015\/07\/25\/business\/us-approves-drug-that-can-sharply-lower-cholesterol-levels.html?_r=0
    \n    [5]<\/a> P Warrener Antimicrob Agents Chemother. 2014; 58:4384<\/p>\n","protected":false},"excerpt":{"rendered":"

    FOR\u00a0PART 1, CLICK HERE Should we assume that the results of this Global Epi Study were the reason why Sanofi became disillusioned about the prospects of KB001? \u00a0Or was it an internal strategic decision based on portfolio-review where KB001 just no longer made the cut? The results of the Global Continue reading The Demise of KB001 (Part 2): An Anti-Pseudomonas Antibody Hits the Dust (instead of Paydirt)<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":1784,"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":[3,18],"tags":[1177,403,1184,1483,891,1178,362,5,1185,207,209,1175,1180,1181,197,801,1179,1187,200,1176,206,1182,79,1186,1183,734,385],"class_list":["post-1769","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-the_news","category-the_viewpoint","tag-anti-pcrv-antibody","tag-antibiotic-blog","tag-ats-guidelines","tag-bankruptcy","tag-cystic-fibrosis","tag-discontinued-mab","tag-fast-track","tag-fda","tag-idsa-guidelines","tag-kalobios","tag-kb001","tag-kb001-a","tag-medimmune","tag-microbiotix","tag-p-aeruginosa","tag-sanofi","tag-sanofi-pasteur","tag-selective-decontamination","tag-shionogi","tag-ttss","tag-type-3-secretion-system","tag-type-iii-secretion-system","tag-vap","tag-vap-bundle","tag-vap-prevention","tag-ventilator-associated-pneumonia","tag-virulence-factors"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/KB-Part-2-NEW.jpg?fit=640%2C181&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-sx","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":1757,"url":"https:\/\/allphasepharma.com\/dir\/2015\/07\/21\/1757\/the-demise-of-kb001-part-i-an-anti-pseudomonas-antibody-hits-the-dust-instead-of-paydirt\/","url_meta":{"origin":1769,"position":0},"title":"The Demise of KB001 (Part 1): An Anti-Pseudomonas Antibody Hits the Dust (Instead of Paydirt)","author":"Harald","date":"July 21, 2015","format":false,"excerpt":"In January this year, Kalobios informed investors that KB001-A had failed to meet efficacy criteria in a Phase 2 trial of cystic fibrosis (CF) patients.\u00a0 In this well-controlled well-executed placebo-controlled trial of182 patients, the primary endpoint and just about every other efficacy endpoint of interest was missed.\u00a0 Neither did KB001\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"KaloBios slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/KaloBios-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/KaloBios-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/KaloBios-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":420,"url":"https:\/\/allphasepharma.com\/dir\/2014\/06\/26\/420\/fighting-p-aeruginosa-part-ii\/","url_meta":{"origin":1769,"position":1},"title":"Fighting P. aeruginosa (Part II)","author":"Harald","date":"June 26, 2014","format":false,"excerpt":"At a still earlier stage of development, we found\u00a0some exciting\u00a0anti-pseudomonal compounds. First, there is BAL-30072, a sulfactam-derivative.\u00a0 It has an interesting dual MoA as it works not only as a traditional B-lactam but also as an Fe-chelator blocking bacteria from accessing this essential nutrient [i].\u00a0 It has very good anti-pseudomonas\u2026","rel":"","context":"In "The News"","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"PipTazo","src":"http:\/\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/06\/PipTazo.jpe","width":350,"height":200},"classes":[]},{"id":5948,"url":"https:\/\/allphasepharma.com\/dir\/2025\/12\/15\/5948\/influenza-vaccination-in-the-elderly\/","url_meta":{"origin":1769,"position":2},"title":"INFLUENZA VACCINATION IN THE ELDERLY","author":"Harald","date":"December 15, 2025","format":false,"excerpt":"In 2024, the ECDC published a detailed review of flu vaccine studies [1].\u00a0 In particular, the report examined published trials of newer flu vaccines.\u00a0 As is well known, the older vaccines provide significant protection, but efficacy is diminished in certain populations.\u00a0 Especially the elderly are at an increased risk of\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/12\/image.png?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/12\/image.png?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/12\/image.png?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/12\/image.png?resize=700%2C400&ssl=1 2x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/12\/image.png?resize=1050%2C600&ssl=1 3x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/12\/image.png?resize=1400%2C800&ssl=1 4x"},"classes":[]},{"id":4540,"url":"https:\/\/allphasepharma.com\/dir\/2025\/06\/21\/4540\/nanobodies-for-autoimmune-diseases\/","url_meta":{"origin":1769,"position":3},"title":"NANOBODIES FOR AUTOIMMUNE DISEASES","author":"Harald","date":"June 21, 2025","format":false,"excerpt":"Thrombotic thrombocytopenic purpura (TTP) is a devastating disease with a downhill course of neurologic, renal and cardiac complications leading to death at a young age if untreated.\u00a0 Thrombocytopenia and thrombosis are its hallmark, with fever, anemia and neurologic deficits. 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