OBJECTIVES: Orphan drugs offer significant clinical benefit, however their cost leads to potentially unsustainable budget impact. US Managed Care Organizations (MCOs) and Pharmacy Benefit Managers (PBMs) often provide coverage, regardless of price and limitations of data at launch, while European payers review data more critically before providing coverage. This poses a challenge to manufacturers of how to design clinical trials that ensure their product will be reimbursed across geographies.

METHODS: The ten highest priced orphan drugs by Wholesale Acquisition Cost (WAC) in the US in 2021 were chosen for this analysis. Health Technology Assessment (HTA) outcomes and rationale for reimbursement decisions were reviewed in Germany, France, and the UK. This was compared to US formulary coverage. The findings informed an online survey which probed on the review of clinical trials for orphan drugs in the US which was sent to 24 US MCO and PBM representatives. In-depth telephone interviews with national decision makers in the US, Germany, France, and the UK were conducted to further understand data requirements across geographies.

RESULTS: MCOs and PBMs in the US are taking minimal action to manage orphan drugs. US payers rely on guidance from the Food and Drug Administration (FDA), often accepting placebo comparators, shorter trial duration, and smaller sample sizes. European payers do not always consider this type of data as sufficient to provide coverage. As a result, trials that are acceptable in the US may not be seen as such to payers in Europe.

CONCLUSIONS: One solution for manufacturers of orphan drugs is to design trials in the most robust way, to satisfy the most stringent markets. Another strategy is to prioritize markets where less data is required at launch. However, this strategy poses several drawbacks, most notably that life-saving treatments would not be available in all markets that need them.