After the cliff: How big pharma is backfilling loss of exclusivity

Pharma has always lived with one eye on the clock. Blockbusters that once defined company fortunes eventually face the reckoning of lost exclusivity, when generics and biosimilars swoop in and cash flows collapse.

This decade brings a cliff of unusual magnitude — more than $200 billion in sales are vulnerable by 2030. The question is whether big pharma can smooth the descent and transition to more productive terrain.

The steepest drop belongs to US pharma major Merck (NYSE: MRK) and its cancer juggernaut Keytruda (pembrolizumab), a drug that has reshaped immuno-oncology and delivered approximately $29.5 billion in 2024. Its key US patent expires in 2028. Merck insists this is a hill, not a cliff, pointing to life-cycle maneuvers and a broadening pipeline. Investors, though, remain nervous: even with steady growth in newer indications, a product of this size cannot be replaced overnight.