OBJECTIVES: Despite high unmet need and limited patient numbers, emerging orphan drugs (OD) must convince the cost-constrained EU5 (France, Germany, Italy, Spain, United Kingdom) of their therapies’ worth. This research examined the HTA and reimbursement landscape for OD in cystic fibrosis (CF) and Duchenne muscular dystrophy (DMD).

METHODS: Across the EU5, 303 pulmonologists and neurologists were surveyed regarding their current and expected prescribing of OD, while 10 payers who influence reimbursement nationally or regionally were interviewed. Secondary research analyzed HTA reviews conducted in the EU5.

RESULTS: Interviewed payers are increasingly reluctant to absorb very high prices for OD with modest or partially proven clinical benefits, as exemplified by ataluren in France, Germany, and Spain. As emerging OD advance in the pipeline, payers indicate that meticulous pivotal trial design—with patient-relevant end points impacting disease progression and quality of life, a well-defined patient population, and optimal trial duration—showcasing unequivocal proof of superiority of emerging OD versus the standard of care (if available) is increasingly crucial for optimal reimbursement across the EU5. Furthermore, payers stress that demonstration of the economic benefit of an OD through cost-effectiveness and cost-utility analysis, and real-world data, will also constitute an important lever in France, Italy, Spain, and the United Kingdom, as drugs offering significant clinical benefit but low cost-effectiveness can be denied reimbursement (e.g., lumacaftor/ivacaftor in the United Kingdom). Indeed, in Germany and the United Kingdom, 33% of DMD patients do not receive ataluren due to access issues, with only 9% of surveyed neurologists in the EU5 indicating that they do not face restrictions to prescribe ataluren.

CONCLUSIONS: OD need to establish acceptable clinical value and—critically—cost-effectiveness in the eyes of healthcare regulatory bodies across the EU5 to secure optimal access. Realistic prices, meaningful discounts/managed-entry agreements, well-designed clinical trials, and persuasive pharmacoeconomic data will facilitate widespread market access.