Nobody Wants to Make the Drug We Need Most

Antimicrobial resistance killed 1.27 million people in 2019 — more than HIV/AIDS or malaria — and projections estimate 39 million cumulative deaths by 2050. Yet the pharmaceutical industry is abandoning antibiotic development. Novartis, Sanofi, AstraZeneca, and Bristol-Myers Squibb have all exited antibiotic R&D, leaving only four major pharmaceutical companies with active programs. The economics are inverted: developing a new antibiotic costs ~$1.5 billion but generates average annual revenues of just $46 million, because the most effective new antibiotics are reserved as last-resort treatments, minimizing sales volume. Achaogen spent 15 years developing plazomicin, received FDA approval and WHO essential medicines listing, earned less than $1 million in its first six months, and filed for bankruptcy. The WHO's 2020 TPPs for antibacterial agents targeting four priority infections remain largely unfilled.

Six bacterial species alone — *E. coli*, *S. aureus*, *K. pneumoniae*, *S. pneumoniae*, *A. baumannii*, *P. aeruginosa* — cause over 250,000 deaths each per year from resistant infections. The highest death rates are in sub-Saharan Africa (27.3 per 100,000). Of 97 antibacterial agents in the clinical pipeline, only 12 targeting WHO priority pathogens are considered innovative, and only 4 of those target "critical" priority pathogens. 82% of researchers focused on innovative antibiotics in 2018 had left the field by 2023. Without systemic economic reform, the pipeline faces collapse within 4-8 years.

Traditional pharmaceutical business models fail because antibiotic stewardship — the correct public health response — directly undermines commercial returns. Reserve antibiotics must be used sparingly to preserve effectiveness, creating a fundamental conflict between public health value and commercial value. The net present value of an antibiotic development project is negative $50 million, compared to +$1.15 billion for a musculoskeletal drug. Venture capital for antimicrobials (2011-2020) totaled $1.6 billion vs. $26.5 billion for oncology. Push incentives (CARB-X, BARDA funding) have sustained early-stage research but don't fix late-stage economics. The AMR Action Fund (~$1 billion from pharma) is time-limited. The UK's "Netflix" subscription model — paying up to 20 million GBP/year per antibiotic regardless of volume — launched in 2024 as the world's first delinked payment, but one country's subscription cannot sustain a global pipeline.

The WHO TPPs define what drugs are needed (oral agents for enteric fever, gonorrhea, and UTI; IV agents for neonatal sepsis; novel mechanisms of action against critical pathogens). The bottleneck is not primarily technical but economic-structural. The US PASTEUR Act ($6 billion over 10 years in delinked subscription contracts) has been introduced but not passed. GARDP (Global Antibiotic Research and Development Partnership) is advancing zoliflodacin for gonorrhea and cefepime-taniborbactam for UTI. Gepotidacin (GSK) is in Phase 3 for gonorrhea and UTI. But without multi-country adoption of delinked payment models, each successful new antibiotic faces the same bankruptcy risk as plazomicin.

A team could model the economic dynamics of antibiotic development under different incentive structures — subscription payments, milestone prizes, transferable exclusivity vouchers — using Monte Carlo simulation of clinical trial outcomes, market adoption, and resistance evolution. The question is: which policy mechanism minimizes the probability of pipeline collapse while maintaining stewardship? Alternatively, a team could design a prototype rapid AST (antimicrobial susceptibility testing) device that enables narrower-spectrum prescribing, reducing the need for broad-spectrum reserve antibiotics and potentially improving their commercial viability by reducing stewardship-imposed volume restrictions. Relevant disciplines: health economics, policy, biomedical engineering, infectious disease.