Enhertu continues to show that it can hit Her2-expressing cancer cells that other drugs cannot reach, priming the Daiichi Sankyo and Astrazeneca asset for dominance across the Her2 space. That means serious competition for players in what now must be called Her2 high. Roche has the most to lose here, although newer products will also suffer – the launch of Seagen’s Her2 kinase inhibitor Tukysa has already been stopped in its tracks after a mere two years by Enhertu’s arrival. In the newly defined Her2-low space there will also be repercussions. The impressive Destiny-Breast04 data likely consign Gilead’s Trodelvy to a last-resort option, given this ADC’s weaker showing in Tropics-02. What of others eyeing this niche? Not many active trials can be found on clinicaltrials.gov of agents specifically going after Her2 low. Most are ADCs – step forward again Seagen, which paid $200m up front for ex-Asia rights to Remegen’s Her2-targeted ADC, disitamab vedotin. Meanwhile, a trispecific from Sanofi and a radiotherapeutic from Bayer provide different mechanistic approaches to watch. Safety is Enhertu’s weak spot so there is room for improvement here; on efficacy, though, a high bar has been set.
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