Reframing the value of reserve antibiotics: how ultra-orphan reimbursement pathways could offer fair and equitable access to new antibiotics.

Antimicrobial resistance is a significant public health challenge. Antibiotic development pipelines are insufficient to tackle this threat, with unfavourable pricing and reimbursement a key factor deterring the development of novel compounds. New antibiotics are priced against generic comparators, and practical and ethical constraints make it challenging to demonstrate superiority in clinical trials. New antibiotics are often classified as reserve antibiotics for a very select group of closely monitored patients with multidrug-resistant infections. The broader value of antibiotics is not routinely considered. 'Pull' incentives have been implemented to encourage development, but are not universally available, and some companies may not qualify. While it may seem counterintuitive at first, many parallels can be drawn between novel antibiotics and orphan/ultra-orphan drugs. Like orphan drugs, novel antibiotics often target small, high-unmet need patient groups, with potential for considerable clinical benefit. Several countries have established specific reimbursement pathways for orphan drugs, allowing higher prices and flexibility for clinical data uncertainty; thus, potentially addressing some of the challenges faced by antibiotics in the absence of dedicated reimbursement pathways. A multidisciplinary advisory board was convened to explore the feasibility of this further and provide recommendations to companies on leveraging orphan drug pathways for antibiotics. This paper presents its recommendations on evidence-generation activities to demonstrate added clinical value and economic savings, along with effective advocacy and collaboration to raise awareness. Key recommendations include conducting additional single-arm trials in last-line patients, generating a natural history control arm, and strengthening collaboration to build advocacy around the threat of AMR.