tag:blogger.com,1999:blog-4287560491211025099.post7620581649128164878..comments2023-09-22T08:24:01.913-04:00Comments on Antibiotics - The Perfect Storm: Antibiotics - Innovation or Clinical Utility?David Shlaeshttp://www.blogger.com/profile/00228776693058791618noreply@blogger.comBlogger6125tag:blogger.com,1999:blog-4287560491211025099.post-5974930465437098812019-12-05T04:02:12.094-05:002019-12-05T04:02:12.094-05:00Great post. Innovative and novel seem to be the b...Great post. Innovative and novel seem to be the buzzwords in antibiotic development. I have heard people say that novel antibiotics won't have issues with resistance. I have also heard that we can charge premium pricing and have high uptake making a viable business case. Both of these are erroneous statements. In the end we should develop to clinical utility.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-4287560491211025099.post-16457146632167628962019-12-02T13:44:49.217-05:002019-12-02T13:44:49.217-05:00I agree completely. "Innovation" has be...I agree completely. "Innovation" has been a bete noir for me. For one thing, it has been used to describe drug products - or candidates (either as non-cross resistant/new target/NCE - or Clinical Utility) - but I also think innovative merits being used to describe the process of drug discovery, as you have - involving the imagination, creativity, risk of going outside the box. It may not be immediately successful, but it is still innovative, to my mind, and it may ultimately prevail. More relevant to your essay - the narrow definition of non-cross resistant is not as meaningful as clinical utility. Among all the beta-lactam/beta-lactamase inhibitor combinations, there are differences that will have strong effects on clinical use. They will probably remain the mainstay of therapy - keeping up (incrementally) with resistance. As the previous commenter noted, new targets may be unlikely to be panaceas. New chemical scaffolds are more relevant. Thanks for bringing this up, Dave.lynnhttps://www.blogger.com/profile/06624656162991974750noreply@blogger.comtag:blogger.com,1999:blog-4287560491211025099.post-86112712951832080042019-11-26T20:13:53.526-05:002019-11-26T20:13:53.526-05:00Hi David, great post. This is a critical point th...Hi David, great post. This is a critical point that is unfortunately lost on many folks in academia, industry, and government. The assumption is often made that new equals better. In particular, it is frequently assumed that inhibiting new biological targets will produce better outcomes. Why is this heuristic so widespread? Perhaps it is partly human nature. The grass is always greener on the other side of the fence, and we easily forget that change can it is often for the worse. However, the new equals better heuristic is actually quite useful for many important thereaputic areas. In the fields of oncology, autoimmunity, cardiovascular disease, and neurodegeneration, the need for new targets is self-evident because highly effective inhibitors of existing targets are not curative and often fail to even durably mitigate disease progression (this is by no means meant to imply that these drugs are not highly valuable to the patients who need them). However, this logic fails in the field of antibiotic discovery where the standard of care in most cases is a rapid and safe CURE. In the field of antibiotics, the data tells us that the current targets are great and may in fact to be the best, as folks like Lynn Silver have long argued. Patients would be better served by focusing on clinical utility as you outlined above, but changing hearts and minds will be challenging so long as "new antibiotic target" is the golden ticket to publishing in high impact journals, securing R01s, getting coverage in the lay press, and getting buy-in from industry R&D governance committeesAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-4287560491211025099.post-36415136518517585312019-11-25T11:14:13.322-05:002019-11-25T11:14:13.322-05:00You continue to provide thoughtful input. Thank y...You continue to provide thoughtful input. Thank you for it. About innovation, in cancer chemotherapy and AIDS, hypertension, and other disease areas, combination therapies have been pursued to advantage. Indeed, BLI/BLA are combinations that have demonstrated great clinical utility. Trimethoprim/ sulfamethoxazole is another winner. But isn't there more room in antibacterial therapy than these two classes?Mark Stidhamhttp://resoluterx.com/noreply@blogger.comtag:blogger.com,1999:blog-4287560491211025099.post-29372519528701987772019-11-25T09:38:33.747-05:002019-11-25T09:38:33.747-05:00Hi David, this is useful input. We will reflect on...Hi David, this is useful input. We will reflect on this with our expert group for the next iteration of the clinical pipeline in 2020. Peter BeyerAnonymoushttps://www.blogger.com/profile/11788368636653544732noreply@blogger.comtag:blogger.com,1999:blog-4287560491211025099.post-77105941310574457212019-11-25T06:02:46.083-05:002019-11-25T06:02:46.083-05:00David, Spot on ! Thanks. Clinical utility is our g...David, Spot on ! Thanks. Clinical utility is our goal, we do not innovate to innovate, we want to develop drugs and technologies that a actually solve a medical problem. It appears this is a real issue currently in the AMR space in particular but also beyond this space.Anonymoushttps://www.blogger.com/profile/14837118427833155093noreply@blogger.com