OBJECTIVES: With many new therapies for overweight and obesity undergoing HTA evaluations in recent years, several therapies continue to experience negative or restricted reimbursement recommendations. Whilst largely due to uncertainties regarding the clinical meaningfulness of trial results, many interventions have failed to meet acceptable affordability and cost-effectiveness thresholds. This study aims to characterize the most common clinical and economic evidentiary critiques, to enable evidence optimization early in the product life cycle.

METHODS: HTA websites for PBAC, CADTH, HAS, and NICE were searched for HTA reports for drugs treating obesity and/or overweight published up to 31 May 2024. Key evidentiary critiques were extracted and mapped.

RESULTS: Thirteen HTA reports were identified across seven approved drugs; four and seven received positive/restricted and negative recommendations respectively, while two reports are undergoing assessment.

HTA agencies questioned the clinical meaningfulness of weight loss achieved, with little evidence to demonstrate how weight loss translates into real-world outcomes, including improvements in weight-related comorbidities such as diabetes and CV complications, and QoL. Many reports highlighted that whilst these therapies are often assessed in conjunction with managed lifestyle interventions, the availability of these across markets varies. Given the chronic nature of the disease, long-term outcomes are critical, with limited follow-up critiqued in ~40% of submissions.

Approximately 50% of treatments failed to meet accepted cost-effectiveness or budget impact thresholds. The main critiques across cost-effectiveness markets highlighted the unsubstantiated claims of long-term benefits assumed in economic models and the difficulty in accurately modelling weight re-gain upon treatment discontinuation.

CONCLUSIONS: Overweight and obesity continues to be one of the most prevalent diseases with a substantial unmet need for effective therapies. Inclusion of long-term follow-up, ensuring endpoints adequately capture impact on comorbidities and increasing certainty in modelled benefits are necessary to enable access to therapies that deliver safe, sustained weight loss and a positive impact on comorbidities.