Oncology Combination Market Access Conundrum in Europe

OBJECTIVES: Examine current market access trends for branded combination oncology therapies in France, Germany, Italy, and the UK

METHODS: We reviewed pricing, reimbursement, and market access when two branded oncology agents are approved for combination use. Because of the extensive use of PD-1s across multiple cancers, we focused on branded combinations with either pembrolizumab or nivolumab. Four branded product combinations were analyzed:

• Nivolumab/cabozantinib(advanced RCC)
• Pembrolizumab/lenvatinib (advanced RCC)
• Pembrolizumab/axitinib (advanced RCC)
• Nivolumab/ipilimumab (melanoma)

RESULTS: Nivolumab/ipilimumab was the only combination therapy from the same manufacturer. Pembrolizumab/lenvatinib was a joint development and commercialization collaboration with favorable access outcomes across all 4 markets. However, the path was more difficult for pembrolizumab/axitinib and nivolumab/cabozantinib where the level of cooperation between manufacturers seemed suboptimal.

• France: Price-volume agreements were re-negotiated for both molecules because of a change in contract conditions, with visible price cuts seen in some cases (e.g. lenvatinib)
• Germany: No price cuts were negotiated on any background therapies; the onus for price negotiations was completely on the manufacturer initiating the new filing/submission
• Italy: Confidential discounts and/or budget caps were re-negotiated for constituent molecules given increasing budget impact (e.g. nivolumab/ipilimumab, nivolumab/lenvatinib)
• UK: Managed access agreements were key to reimbursement (e.g. nivolumab/ipilimumab; pembrolizumab/lenvatinib). However, given the central role of cost-effectiveness, no reimbursement (e.g., pembrolizumab/axitinib) or terminated appraisal (e.g., nivolumab/cabozantinib) seen when manufacturers are unwilling to share associated risks.

CONCLUSIONS: The cost of oncology therapies with ≥2 on-patent medicines in combination poses a challenge for affordability, funding, and access. The manufacturer of an existing branded background therapy does not always have the incentive to renegotiate a price unless there is an agreement to co-develop and/or co-commercialize. With several branded oncology combinations in development, new frameworks for valuing and paying for them and maintaining incentives for investment are key.