周末医疗健康动态：耐药菌危机-全球性威胁、创新刚需与印度机遇

Courtney Breen+19173448407 courtney.breen@bernsteinsg.comLee Hambright+19173448429 lee.hambright@bernsteinsg.comSusannah Ludwig+41582723127 susannah.ludwig@bernsteinsg.comMiki Sogi, Ph.D.+81367776991 mikisogi@bernsteinsg.comRebecca Liang,Ph.D.+85221232656rebeccaliang@bernsteinsg.comEve Burstein+19173448313 eve.burstein@bernsteinsg.comJustin Smith+442077625899 justin.smith@bernsteinsg.comWilliam Pickering,MD+19173448340 william.pickering@bernsteinsg.comJeffrey Walch,MD, Ph.D.+1917344 8613 jeffrey.walch@bernsteinsg.comDelphineLe Louet+33142139293 delphine.le-louet@bernsteinsg.comLance Wilkes+19173448501lance.wilkes@bernsteinsg.com representsthe class ofbacteria thatare initially susceptible to aparticular class ofantibiotic;however,an adaptive and evolutionarystrategy isnowresistanttothe impact antibiotics.Bothaccidentalmutations andthe introductionof foreign genetic material canresult in acquired resistance.On the other hand, intrinsic resistanceincludes those bacteria that, right from the beginning, exhibitresistanceabilityagainst the antibiotic as theylack the potentialantibiotic target in their system.Duetoacquired resistance,theviabilityof potential pathogenic bacteria (bothGram-positiveand Gram-negative)is continuously increasing in every niche ofthe biosphere, complicating the overall scenario.Our study ofclinical publications onthistopic suggests that thecombination ofacquired and intrinsic resistance are the drivers of exponentiallyincreasingmortalityburden in AMR.We estimate from theLancetanalysis of The GRAM 2024thatbacterialAMR was directlyresponsibleforabout1.2Mnglobaldeaths in2021andassociated with in about 4.7Mn deaths.We estimate that by 2050,direct AMRdeaths canreachabouttwomillionannuallyandassociated deaths about eight-ninemillionannually.Weestimatefrom the WHO-cited World Bank reports that AMR could createUS$1tnofadditional healthcarecostsby2050andUS$2tntoUS$3.4tn of annualGDPlossesby2030.Resistantinfectionsincrease lengthof stay,IcUutilization,diagnostic intensityuse of second-line and third-line drugs, isolation costs andreadmissions. PROVIDERS,PAYERS,ANDPHARMACOS?Antimicrobial resistance(AMR),occurs whenbacteria,viruses fungiorparasitesevolvemechanismstosurvivedrugsthatpreviously killed them. In pharma, it is bacterial resistance toantibiotics. The clinical result is hence simple:first antibioticfails,treatmentisdelayed,infectionprogresses,hospitalstayextends,andmortality rises.Our research of academicpublications and medical literature suggests that the AMR is causedby three fundamental factors. We believe the first reason is the highrise in antimicrobialuse overthe pastfewdecades.The secondwebelieve is thatmostof the time,patients are unableto appropriatelyfollow the therapeutic guidelines. The third reason we believe isevenmore convoluted,within aparticularclass ofantibiotics,therearen'tmanynewmedications being developedto replacethosethatare becoming ineffective owing to increaseddrug resistance. At a biology level,resistance is an evolutionary selectionproblemAntibiotic exposurekills susceptible organisms and leavesbehindorganismswith survival advantages.These advantages cancomefrombeta-lactamasesthatdestroybeta-lactamantibiotics,carbapenemsthatneutralizelast-line carbapenems,effluxpumpsthat push drugs out of the bacterial cell, target-sitemutationsand plasmid-mediated genetransferthatspreads resistancebetweenbacteria.Why do thesethings matter commercially?Becausetheyturncheapgeneric antibiotics into inadequatetherapy andforcehospitals into expensivediagnostics,IcU careand last-line injectables. Thus, the two broad categories of Globally,India is one ofthe highest-exposedmarkets.Our researchof Indian healthcare system data suggests that In India over thelastfiveyears,bacterial infectionscaused anaverage ofabout1.5-1.6 Mn deaths of which AMR was associated in more than 60% deaths. We believe this also results in an unsettling trend that Indiahasa large sepsis poolwithourestimateof incidenceatabout 540to 640 per 100,000 population,and mortalityof 25to 30%.EXHIBIT1:Multiple bacterial resistance mechanismsreduce NHS England's Quality Premium, introduced way back in 2015, rewardedlocalClinicalCommissioningGroupsfinanciallyforcutting primary-care prescribing-where~74-80%of antibioticsaredispensed.Thisprogramtargeteda1%reductionintotal itemsanda 10% cut inbroad-spectrumuse.Our researchof follow-upstudyfromImperial/PHEevaluationsuggeststhat~8.2%relativefallin total antibiotic items and an 18.9% drop in broad-spectrumprescribing. On the supply side,the United Kingdom pioneered theworld's first"Netflix-style" subscription (pull) model-the mirrorimage of Japan'sdemand-sidefee.Since July2022,NHSEnglandpays a fixed annualfee (initially up to 10 million/product) de-linkedfrom sales volumeforPfizer's ceftazidime-avibactam (Zavicefta)and Shionogi's cefiderocol (Fetcroja), rewarding value to the healthsystem ratherthan units sold (NICE;Applied Health Econ &HealthPolicy). In May 2024 the UK