Zynlonta gets squeezed

ADC Therapeutics’ Zynlonta, an anti-CD19 antibody-drug conjugate, was approved nearly three years ago, and in 2023 generated sales of just $69m. That’s not a great endorsement for a drug that uses a modality at the forefront of current oncology strategies, and now ADC has another small worry: Lotis-5, the phase 3 trial designed to confirm that accelerated approval, has experienced high rates of censoring, it was revealed today, meaning that more than the planned 350 patients might be needed to maintain powering. One problem is that the setting in question, second-line or later diffuse large B-cell lymphoma, is changing fast, with CD19-directed Car-T therapy expanding from relapsed/refractory to second-line use, and anti-CD20 T-cell engagers taking a slice of the late-line pie. Not only did ADC pick a highly competitive target in CD19, Zynlonta uses a tesirine payload (also used in AbbVie’s doomed Rova-T) rather than topo1 inhibition, the current industry favourite, and numerous Zynlonta study discontinuations show how ADC has had to chop and change plans. Zynlonta always looked like a marginal product, and though it seems likely to remain on the market it’s now being squeezed hard by competitors.

Selected trials of Zynlonta

Source: OncologyPipeline.