{"id":2061,"date":"2015-10-20T16:38:16","date_gmt":"2015-10-20T20:38:16","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=2061"},"modified":"2017-04-07T08:47:11","modified_gmt":"2017-04-07T12:47:11","slug":"polyphor-pol7080-and-the-journey-to-the-land-of-pyocyanea-part-2","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/10\/20\/2061\/polyphor-pol7080-and-the-journey-to-the-land-of-pyocyanea-part-2\/","title":{"rendered":"Polyphor POL7080 And The Journey to The Land of Pyocyanea\u00a0 (Part 2)"},"content":{"rendered":"

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

Roche\u2019s current Phase 2 program is strangely ambiguous. RG-7929 has not made it into www.clinicaltrials.gov yet, only POL7080 is listed. An uncontrolled open label study in \u201cpatients with non-CF acute exacerbation of bronchiectasis due to P. aeruginosa requiring IV treatment\u201d is enrolling. Well, good luck finding those patients! At best, this is a\u00a0safety study; an assessment of efficacy (by measuring reduction in CFU) will not be possible in such a small cohort (N= 20).<\/p>\n

More to the point is a Phase 2 VAP study. This\u00a0is also a small open-label uncontrolled trial (N=25) for patients with \u201csuspected or possible\u201d P. aeruginosa lung infection. This study will provide some useful PK information in the target population. With POL7080 given together\u00a0with SoC, it will not permit an efficacy assessment either.<\/p>\n

Interestingly,\u00a0no dosing information is provided for any\u00a0Phase 2 study; it seems that the appropriate dose is still in question.<\/p>\n

In summary, we cannot expect more than PK\/PD information and tiny bit more safety data from the current Phase 2 program. This is not enough to jump into a costly and – we would argue – highly risky Phase 3 program. It would make sense for\u00a0Roche to\u00a0add a mid-size Phase 2 trial to get a\u00a0preliminary read-out on efficacy. This would\u00a0give the team time to structure the path for Phase 3 and the submission package.<\/p>\n

The POL7080 development program is very difficult and getting it right will take imagination. We wish the Roche\/Polyphor team all the best for their Health Authority meetings. VABP has proven to be a mine field for many drugs already, even for those where we would have expected a home run. Think about doripenem and tigecycline, but they are not alone. Nowadays, recruitment has become more difficult as cases of VAP are disappearing, partly because of the CMS penalties for hospitals reporting\u00a0VABP cases, partly because the VAP \u2018bundle\u2019 of preventative measures has really made a difference.<\/p>\n

Let\u2019s also be clear: there is no other indication for POL7080 to pursue than VABP.\u00a0 P. aeruginosa infection in skin infections or burns, UTI and malignant external otitis are just too rare for prospective study. CF patients are routinely receiving\u00a0so many drugs, including IV and aerosol antipseudomonas agents, making it impossible to study POL7080 in this polypharmacy environment. POL7080 is a drug for serious P. aeruginosa infection, not for folliculitis or hot tub rash. But bacteremia \/ sepsis is also not an indication anyone would want to tackle with a new antibiotic coming right from the start.<\/p>\n

Cubist proved that a narrow-spectrum drug like daptomycin can be developed: Their S. aureus endocarditis trial\u00a0was highly innovative in design, difficult to execute and high risk overall but the payback for these\u00a0efforts was enormous. Somehow I doubt that any large pharma company could have done what this small dedicated VC company could pull off.\u00a0 Hats off to Francis Tally and his team of trailblazers at Cubist.<\/p>\n

In contrast to MRSA endocarditis, P. aeruginosa endocarditis is no longer\u00a0common – not even in the Detroit area. Such a study would require\u00a0a huge effort and strong commitment, and still take too long to execute.<\/p>\n

Unfortunately, \u201cexacerbation of bronchiectasis due to P.aeruginosa in need for IV therapy\u201d is not<\/span> the sweet spot for POL7080. Let\u2019s hope that Roche develops a quick diagnostic test and comes up with a workable plan for Phase 3 quickly.<\/p>\n

Part 3 to follow shortly – HHR<\/span><\/p>\n

Abbreviations:<\/strong><\/p>\n

SoC\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 standard-of-care
\nCF \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 cystic fibrosis
\nVAP\/VABP \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0ventilator-associated (bacterial) pneumonia
\nCMS\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Center for Medicare\/Medicaid Services<\/p>\n","protected":false},"excerpt":{"rendered":"

Roche\u2019s current Phase 2 program is strangely ambiguous. RG-7929 has not made it into www.clinicaltrials.gov yet, only POL7080 is listed. An uncontrolled open label study in \u201cpatients with non-CF acute exacerbation of bronchiectasis due to P. aeruginosa requiring IV treatment\u201d is enrolling. Well, good luck finding those patients! At best, Continue reading Polyphor POL7080 And The Journey to The Land of Pyocyanea\u00a0 (Part 2)<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":2062,"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":[403,691,892,229,92,228,741,432,233,5,91,1376,83,197,923,173,1358,184,262,43,426,1375,356,79,1186],"class_list":["post-2061","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-qidp_antibiotic","category-the_news","category-the_viewpoint","tag-antibiotic-blog","tag-bacteremia","tag-bronchiectasis","tag-cubicin","tag-cubist","tag-daptomycin","tag-doribax","tag-doripenem","tag-endocarditis","tag-fda","tag-francis-tally","tag-malignant-otitis-externa","tag-mrsa","tag-p-aeruginosa","tag-pol7080","tag-polyphor","tag-rg-7929","tag-roche","tag-sepsis","tag-tigecycline","tag-tygacil","tag-uti","tag-vabp","tag-vap","tag-vap-bundle"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-P2.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-xf","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":1981,"url":"https:\/\/allphasepharma.com\/dir\/2015\/10\/05\/1981\/polyphor-pol-7080-and-the-journey-to-the-land-of-pyocyanea-part-1\/","url_meta":{"origin":2061,"position":0},"title":"Polyphor POL7080 And The Journey to The Land of Pyocyanea\u00a0 (Part 1)","author":"Harald","date":"October 5, 2015","format":false,"excerpt":"When Roche inlicensed Polyphor\u2019s anti-pseudomonas drug POL7080 in November 2013, it marked a turning point. It seemed that Big Pharma that had all but abandoned the field in the last decade and was getting engaged in anti-infectives again. When a company with as\u00a0much experience in antibiotic drug development as Roche\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"bridge Pyocyanea copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-copy.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-copy.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-copy.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2064,"url":"https:\/\/allphasepharma.com\/dir\/2015\/10\/22\/2064\/polyphor-pol7080-and-the-journey-to-the-land-of-pyocyanea-part-3\/","url_meta":{"origin":2061,"position":1},"title":"Polyphor POL7080 And The Journey to The Land of Pyocyanea (Part 3)","author":"Harald","date":"October 22, 2015","format":false,"excerpt":"VABP is clearly the main\u00a0indication to be pursued by a drug like POL7080.\u00a0 Here is the question: How to conduct a study demonstrating efficacy for a drug which only has a\u00a0single-organism spectrum? \u00a0Which is actually no spectrum at all. \u00a0Existing guidelines for the development of ID drugs are indication-driven, with\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"bridge Pyocyanea-P3","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-P3.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-P3.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-P3.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1769,"url":"https:\/\/allphasepharma.com\/dir\/2015\/07\/28\/1769\/the-demise-of-kb001-part-2-an-anti-pseudomonas-antibody-hits-the-dust-instead-of-paydirt\/","url_meta":{"origin":2061,"position":2},"title":"The Demise of KB001 (Part 2): An Anti-Pseudomonas Antibody Hits the Dust (instead of Paydirt)","author":"Harald","date":"July 28, 2015","format":false,"excerpt":"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\u2026","rel":"","context":"In "The News"","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"KB Part 2 NEW","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/KB-Part-2-NEW.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/KB-Part-2-NEW.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/KB-Part-2-NEW.jpg?resize=525%2C300 1.5x"},"classes":[]},{"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":2061,"position":3},"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":2993,"url":"https:\/\/allphasepharma.com\/dir\/2017\/01\/09\/2993\/aradigm-lost-orbit-hayward-problem\/","url_meta":{"origin":2061,"position":4},"title":"Aradigm Lost in ORBIT \u2013 Hayward, We Have a Problem","author":"Harald","date":"January 9, 2017","format":false,"excerpt":"It is interesting to see how often a discussion of study results moves from microbiology to clinical significance to statistical analysis details. When an antibiotic is not evaluated on the basis of its antimicrobial activity but on its ability to change a clinically relevant measure (the \u201cfeel, function, survive\u201d mantra\u2026","rel":"","context":"In "QIDP Antibiotics"","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\/01\/Aradigm-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/Aradigm-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/Aradigm-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1362,"url":"https:\/\/allphasepharma.com\/dir\/2015\/04\/08\/1362\/arties-law-avoid-bad-advice-and-dont-follow-mission-impossible-advice\/","url_meta":{"origin":2061,"position":5},"title":"Artie\u2019s Law: Avoid Bad Advice and Don\u2019t Follow \u2018Mission Impossible\u2019 Advice","author":"Harald","date":"April 8, 2015","format":false,"excerpt":"In this day and age, few truly broad spectrum antibiotics are in development, although this does not hold true for narrow-spectrums.\u00a0 Just think of all the MRSA drugs (quinolones, FabI inhibitors), the pseudomonas drugs (NCEs and monoclonals) or some narrow spectrum drugs that will need to be tested in MDR\u2026","rel":"","context":"In "The Viewpoint"","block_context":{"text":"The Viewpoint","link":"https:\/\/allphasepharma.com\/dir\/category\/the_viewpoint\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2061","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=2061"}],"version-history":[{"count":7,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2061\/revisions"}],"predecessor-version":[{"id":3290,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2061\/revisions\/3290"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media\/2062"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=2061"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=2061"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=2061"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}