A pivotal trial of Bayer’s antibody-drug conjugate (ADC) anetumab ravtansine has missed its primary endpoint. The drug failed to improve progression-free survival in mesothelioma patients, causing the stocks of Bayer’s collaborators ImmunoGen and MorphoSys to slip.
Investigators enrolled 248 patients with advanced malignant pleural mesothelioma (MPM) that overexpressed the mesothelin protein who had advanced after first-line treatment. The subjects received either an infusion of anetumab ravtansine every three weeks or weekly dosings of the chemotherapy vinorelbine. Patients continued on these regimens until their cancer progressed or they withdrew from the trial for other reasons.
Anetumab ravtansine failed to delay disease progression in the potentially-pivotal trial. MorphoSys broke news of its partner’s failure without providing PFS numbers for the anetumab ravtansine or vinorelbine cohorts, or any other details beyond the fact the study missed its primary endpoint.
The data, while terrible enough to sink the mesothelioma monotherapy trial, haven’t prompted Bayer to pull the plug on the rest of its anetumab ravtansine clinical development program. Bayer and its collaborators are enrolling patients with a range of cancers in phase 1 and 2 trials of the ADC. The list includes phase 1b trials that are assessing anetumab ravtansine in combination with other drugs in patients with platinum-resistant ovarian cancer and other solid tumors.
Anetumab ravtansine may get a second chance in mesothelioma, too. The National Cancer Institute plans to look at the ADC in combination with Merck’s checkpoint inhibitor Keytruda next year, although the organization plotted out that phase 1/2 before news of the monotherapy failure broke.
The setback will dampen expectations for future readouts related to a drug that was seen as a hot prospect by some of the companies involved in its development. MorphoSys, which contributed the mesothelin-targeting antibody to anetumab ravtansine, listed the candidate as one to watch in a company update last year. The German biotech talked up the preclinical and phase 1 data that had propelled the candidate into the potentially-pivotal phase 2 trial.
Anetumab ravtansine’s failure to go the needle in that trial shuts off an anticipated source of near-term income for MorphoSys. The ADC is one of a clutch of partnered candidates MorphoSys envisaged generating income in the years to come. MorphoSys dialed up its in-house R&D spending in anticipation of the revenue streams coming online. But with Novartis’ bimagrumab and now anetumab ravtansine suffering setbacks, Johnson & Johnson’s Tremfya (guselkumab) is the only one of MorphoSys’ partnered programs to come through late-phase trials unscathed.
Shares in MorphoSys fell 5% before recovering somewhat following the news. ImmunoGen, which is in line for royalties for providing ADC technology, also saw its stock slip by 4%.
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