AbbVie axes multi-billion cancer flop Rova-T after another trial fails

AbbVie has axed its troubled lung cancer drug Rova-T, after another trial failure from the drug that is turning out to be an expensive flop, costing almost $10 billion so far.

As it searched for new drugs to replace revenues lost from the patent expiry of its mega-blockbuster Humira, AbbVie snapped up Rova-T’s developer Stemcentrx in 2016 for $5.8 billion.

But the gamble has not paid off after yet another trial disaster from the antibody-drug conjugate, full name rovalpituzumab tesirine.

AbbVie already took an impairment charge of $4 billion earlier this year following a previous Rova-T trial failure, and there are doubts about the other compounds that AbbVie added to its pipeline following the Stemcentrx deal.

The idea behind Rova-T is to use the antibody to target delta-like protein 3 (DLL3), an antigen expressed in more than 80% of small cell lung cancer tumours, prevalent in tumour cells and cancer stem cells but not healthy tissue.

Then the cytotoxic agent tesirine could be delivered directly to the DLL-3 expressing cancer cells.

It sounds great in theory but in practice it’s not working – AbbVie announced that it has ended the phase 3 MERU trial of Rova-T as first line maintenance therapy in advanced small-cell lung cancer (SCLC) after it demonstrated no survival benefit in a pre-planned interim analysis comparing it with placebo.

The company made the decision based on a recommendation from the trial’s Independent Data Monitoring Committee, which cited a lack of survival benefit compared with placebo.

The Rova-T R&D programme has been terminated, and AbbVie said it will “move forward prioritising other development programmes within its oncology pipeline”.

This follows other issues with Rova-T during development - AbbVie axed the phase 3 TAHOE study in second line advanced SCLC late last year.

In that trial the company found survival was shorter in patients treated with Rova-T compared with the standard care arm treated with topotecan.

And unconvincing results from a phase 2 study in third line relapsed/refractory SCLC early last year prompted AbbVie to pull plans for an accelerated approval with the FDA.

The suspicion is centred on the tesirine cytotoxic component of the drug, also used in other compounds from Stemcentrx, which could be causing side-effects affecting patients’ survival chances.

Regardless of whether these other drugs succeed, Rova-T is already becoming a salutary lesson about the high stakes gamble that is drug development.