A Decade of PD-1 Inhibitors: Keytruda and Opdivo Transform Global Cancer Treatment Landscape

Key Insights

• Keytruda and Opdivo have achieved remarkable market penetration over the past decade, with Keytruda available in 59 countries across 40 indications and Opdivo present in 53 countries with 13 approved indications.
• Both drugs show distinct pricing patterns across major markets, with lowest launch prices in Asian markets and significant price erosion in Japan, Germany, and France, while maintaining stable prices in the US, UK, Spain, and China.
• Health Technology Assessment outcomes reveal similar approval patterns for both drugs, with bladder cancer emerging as a challenging indication, while both continue to expand into new therapeutic areas.

Ten years after their initial approvals, PD-1 inhibitors Keytruda (pembrolizumab) and Opdivo (nivolumab) have fundamentally transformed the oncology treatment landscape, establishing themselves as cornerstone immunotherapy agents across multiple cancer types.

Global Market Expansion and Regulatory Success

Keytruda's journey began with FDA approval in September 2014, followed by rapid market entry just four days later. The drug has since established presence in 59 countries, entering a new market approximately every 64 days. With reimbursement secured in 60% of these markets and approval across 40 indications, Keytruda's global footprint is substantial.

Opdivo, while receiving FDA approval three months after Keytruda, actually pioneered the market with its initial Japanese approval in July 2014. The drug has since expanded to 53 countries, achieving reimbursement in 68% of these markets, with new market entry occurring every 65 days on average. However, Opdivo's indication portfolio remains more focused, with 13 approved indications compared to Keytruda's 40.

Strategic Pricing Dynamics Across Major Markets

The pricing landscape reveals intriguing regional variations. In Asian markets, both drugs launched at their lowest price points - Keytruda at $23.82 per unit/mg in Japan and Opdivo at $13.04 per unit/mg in China. Opdivo's entry into China's National Reimbursement Drug List (NRDL) required significant price negotiations, resulting in a 70% lower launch price compared to its US pricing.

Over the decade, price evolution has varied significantly by region:

• Japan, Germany, and France have seen price erosion for both drugs, ranging from 7.52% to 48% for Keytruda
• Opdivo experienced more extensive price reductions, ranging from 23% to 82% across these markets plus Italy
• Japan's biennial price reviews, which shifted to annual revisions in 2022, have particularly impacted both drugs
• The US stands alone among major markets in showing price increases
• Prices have remained stable since launch in Spain, the UK, and China

Health Technology Assessment Performance

Analysis of HTA evaluations (130 for Keytruda and 105 for Opdivo) across major markets reveals similar patterns of acceptance and rejection. Notable challenges include:

• Multiple rejections in bladder cancer indications for both drugs
• Keytruda faced additional challenges in head and neck cancer and soft tissue sarcoma
• France has rejected three indications for each drug, primarily due to insufficient SMR ratings

Looking ahead, both drugs continue to pursue indication expansions, with Keytruda focusing on lung cancer and Opdivo on bladder cancer, though the latter may face continued challenges based on historical assessment patterns.

Market Impact and Future Outlook

Despite growing competition in the PD-1 inhibitor space, both Keytruda and Opdivo have maintained strong market positions through strategic pricing, systematic global expansion, and continuous indication development. Their success has established new paradigms in cancer immunotherapy while highlighting the complexities of global pharmaceutical market access and pricing strategies.