{"id":2446,"date":"2016-04-21T13:22:26","date_gmt":"2016-04-21T17:22:26","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=2446"},"modified":"2016-04-21T21:34:50","modified_gmt":"2016-04-22T01:34:50","slug":"quo-vadis-cdi-drugs","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2016\/04\/21\/2446\/quo-vadis-cdi-drugs\/","title":{"rendered":"Quo Vadis, CDI Drugs?"},"content":{"rendered":"

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

There are only 3 CDI drugs in wider clinical use: vancomycin, metronidazole, and fidaxomicin. They are from totally different classes and have almost nothing in common except for proven efficacy in C. difficile infection (CDI).<\/p>\n

Like vancomycin, the entire group of glycopeptide drugs seems to have good activity against C. difficile. Based on microbiology and animal data they could all be used interchangeably if need be.\u00a0 Differences exist but are probably not clinically relevant. For instance, telavancin MICs are lower than for vancomycin but with a similar MoA it is hard to see any differentiation that would justify a separate CDI development for this or any of the other old glycopeptides.<\/p>\n

Fidoxamicin has moved the goal post regarding efficacy. It is a macrocyclic antibiotic and as active as vancomycin or metronidazole. In addition, it has some unexpected features, both good and not so good: it reduces relapse rates in half in first-time responders, but not so for patients infected with the BI\/NAP1\/027 hypervirulent strain.<\/p>\n

No doubt, there is room for improvement on several fronts. Besides the key features of efficacy and safety, the next CDI drug should have a very low relapse rate (< 12%) and only minimally affect the gut microbiome. These two goals are interconnected: it stands to reason that less disruption of the gut flora will also protect from relapse.\u00a0This can only be avoided with a more C. difficile \u2013 specific agent. Likewise, sustained clinical response in patients infected with the hypervirulent BI\/NAP1\/027 serotype would seem of great importance. Taken together, this makes the target profile for the next CDI drug multi-dimensional.<\/p>\n

Recently some structurally very different NCEs have entered the race to replace the vancomycin – metronidazole – fidaxomicin troika. Here our list without any guarantee for completeness:<\/p>\n

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

 <\/p>\n

Industry consolidation may affect\u00a0development efforts of\u00a0CDI drugs as well. It is hard to see how Merck \u2013 after acquiring\u00a0Cubist \u2013 would continue work on all the CDI drugs it now has in its portfolio.<\/p>\n

Fidaxomicin was priced so high it self-destructed in the market; it may now be too late to turn things around. Then there is\u00a0the anti-toxin cocktail of 2 monoclonal antibodies directed at clostridial toxins TcdA and TcdB which is \u2018under consideration\u2019 for development.\u00a0 In a sizeable (N=200) Phase 2 study, the monoclonals improved C. difficile recurrence rates significantly and by a healthy\u00a0margin when used in combination with either vancomycin or metronidazole. Clinicaltrials.gov lists a\u00a0Phase 3 study as completed since November 2015; hence, it is time for a publication, one would think.<\/p>\n

Antitoxin therapy is highly effective in the other 2 clostridial diseases, tetanus and gas gangrene, hence, there is indirect proof of concept. However, tolevamer, an orally administered toxin binder did not fare well in Phase 3 testing (despite\u00a0promising Phase 2 results).\u00a0

Surotomycin (CB-183,315) is a daptomycin derivative and structurallly different from the other glyco(lipo)peptides<\/span><\/p>\n<\/div><\/p>\n

Surotomycin (CB-183,315 or MK-4261) is not listed on the Merck list of drug development candidates, for unclear reasons. This\u00a0daptomycin derivative should not be discarded too quickly. It is structurally quite different from\u00a0vancomycin, oritavancin, telavancin and dalbavancin. It remains to be seen whether the Cubist team – now at Merck – \u00a0is able to get such finer points across to their new management.<\/p>\n

=========================================================================<\/p>\n

NOTE ADDED IN PROOF
\nThe poster of a large Phase 3 surotomycin study was presented at ECCMID 2016 \/ Amsterdam. The drug showed essentially equivalent efficacy to vancomycin. Unfortunately, the primary efficacy endpoint narrowly missed\u00a0the 10% non-inferiority delta;\u00a0the 95% confidence interval boundaries were\u00a0[-11, 1.9].\u00a0<\/span><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

There are only 3 CDI drugs in wider clinical use: vancomycin, metronidazole, and fidaxomicin. They are from totally different classes and have almost nothing in common except for proven efficacy in C. difficile infection (CDI). Like vancomycin, the entire group of glycopeptide drugs seems to have good activity against C. Continue reading Quo Vadis, CDI Drugs?<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":2447,"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":[227,3,18],"tags":[593,1619,1271,403,1601,1617,1620,1622,608,1607,75,1594,1623,229,66,85,228,89,597,1589,1624,409,1600,88,612,1605,70,1608,1583,304,588,1598,1618,1215,1609,1096,1610,1615,174,1614,1613,234,67,655,1596,1611,1616,1621,1612,602,613,1595,74,1604,263,480,1606,426,1593,48,86,1599,440],"class_list":["post-2446","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","category-the_viewpoint","tag-actelion","tag-actoxumab","tag-allphase-pharma-consulting","tag-antibiotic-blog","tag-antitoxin","tag-bacitracin","tag-bezlotoxumab","tag-binap1027","tag-cadazolid","tag-cb-183315","tag-cdi","tag-clostridium-difficile","tag-crestone","tag-cubicin","tag-dalbavancin","tag-dalvance","tag-daptomycin","tag-dificid","tag-durata","tag-eccmid","tag-ef-g","tag-ef-tu","tag-enterococcus-faecium","tag-fidaxomicin","tag-fusidic-acid","tag-gas-gangrene","tag-glycopeptide","tag-glycopeptide-antibiotics","tag-harald-reinhart","tag-lff-571","tag-merck","tag-metronidazole","tag-mk-3415a","tag-mk-4261","tag-nanotherapeutics","tag-niaid","tag-nitazoxamide","tag-novacta","tag-novartis","tag-nvb-302","tag-opt-80","tag-orbactiv","tag-oritavancin","tag-pfizer","tag-ramoplanin","tag-ridinilazole","tag-rifaximin","tag-salix","tag-smt19969","tag-summit","tag-surotomycin","tag-teicoplanin","tag-telavancin","tag-tetanus","tag-tetracycline","tag-the-medicines-company","tag-tolevamer","tag-tygacil","tag-vancocin","tag-vancomycin","tag-vibativ","tag-vre","tag-wyeth"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/04\/CDI-slider-copy.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-Ds","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":249,"url":"https:\/\/allphasepharma.com\/dir\/2014\/06\/05\/249\/here-they-are-dalbavancin-oritavancin-the-new-long-acting-lipoglycopeptides\/","url_meta":{"origin":2446,"position":0},"title":"Here They Are: Dalbavancin and Oritavancin \u2013 The New Long-Acting Lipoglycopeptides","author":"Harald","date":"June 5, 2014","format":false,"excerpt":"The development history of glycopeptide drugs is anything but normal.\u00a0 Daptomycin (Cubicin\u00ae) was abandoned by Lilly but resurrected by Francis Tally at Cubist by adjusting the dosing schedule to once daily and careful uptitration.\u00a0 The drug did superbly in a landmark endocarditis trial and everything looked rosy.\u00a0 Then we learned\u2026","rel":"","context":"In "The News"","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2205,"url":"https:\/\/allphasepharma.com\/dir\/2015\/12\/23\/2205\/qidp-antibiotics-2015-year-end-update\/","url_meta":{"origin":2446,"position":1},"title":"QIDP Antibiotics – 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 "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\/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":2563,"url":"https:\/\/allphasepharma.com\/dir\/2016\/06\/22\/2563\/progress-report-new-antibacterials-in-the-fight-against-mdr-bacteria\/","url_meta":{"origin":2446,"position":2},"title":"Progress Report: New Antibacterials In the Fight against MDR Bacteria","author":"Harald","date":"June 22, 2016","format":false,"excerpt":"Since the beginning of this millennium we have seen antibiotic R&D dwindle year after year. There are many reasons for this; while economics are often cited for this decline, the FDA and the \u2018Guideline Wars\u2019, i.e., those never ending discussions about regulatory requirements, have contributed to this trend in a\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"Pipeline - slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/06\/Pipeline-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/06\/Pipeline-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/06\/Pipeline-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1543,"url":"https:\/\/allphasepharma.com\/dir\/2015\/06\/12\/1543\/vancomycin-vs-tmpsmx-for-mrsa-not-the-final-word\/","url_meta":{"origin":2446,"position":3},"title":"Vancomycin vs TMP\/SMX for MRSA \u2013 Not the Final Word","author":"Harald","date":"June 12, 2015","format":false,"excerpt":"Vancomycin got a bad reputation since the early 90ies when it became clear that it\u00a0was slow to provide clinical improvement and microbiologic cure in MRSA patients. \u00a0It was associated with prolonged bacteremia even when combined with rifampin\u00a0[1]. \u00a0And for MSSA, anti-staph penicillins like nafcillin were always the better choice. Then,\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"vanquish","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/vanquish.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":3116,"url":"https:\/\/allphasepharma.com\/dir\/2017\/01\/30\/3116\/txa-709-kid-qidp-block\/","url_meta":{"origin":2446,"position":4},"title":"TXA-709 –\u00a0 New Kid on the Block","author":"Harald","date":"January 30, 2017","format":false,"excerpt":"When searching for FtsZ inhibitors on PubMed, there are 187 hits. When narrowing down the search looking for clinical trials only, there are none. Taxis Pharmaceuticals obtained QIDP status for its candidate drug TXA-709 in late 2016 and it is still in preclinical testing. The drug\u2019s target, bacterial replication machinery\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\/FtsZ-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/FtsZ-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/FtsZ-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":3577,"url":"https:\/\/allphasepharma.com\/dir\/2025\/06\/02\/3577\/__trashed-2__trashed\/","url_meta":{"origin":2446,"position":5},"title":"The 10 x \u201920 Initiative – A Retrospective","author":"Harald","date":"June 2, 2025","format":false,"excerpt":"It started all so well with fanfare and great expectations.\u00a0Fifteen years ago, the 10 x \u201920 initiative got underway. Its goals were spelled out clearly: To \u2018Pursue a Global Commitment to Develop 10 New Antibacterial Drugs by 2020 \u2019[3].\u00a0 It was driven by ID clinicians and by antibiotic developers concerned\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"BBND","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2020\/06\/BBND.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2020\/06\/BBND.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2020\/06\/BBND.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2446","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=2446"}],"version-history":[{"count":9,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2446\/revisions"}],"predecessor-version":[{"id":2462,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2446\/revisions\/2462"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media\/2447"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=2446"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=2446"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=2446"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}