Roche’s ulcerative colitis drug etrolizumab looks shaky after data roll-out

Roche’s late-stage trial programme for ulcerative colitis candidate etrolizumab has generated some positive and negative results, but leans firmly towards the latter.

The Swiss drugmaker has acknowledged that the dual-acting anti-integrin antibody – which is trying to chase down Takeda’s blockbuster Entyvio in UC – generated “disappointing” results from the programme, which is billed as the largest ever undertaken in inflammatory bowel disease (IBD).

On the plus side, etrolizumab met the primary endpoint of improving remission compared to placebo in HIBISCUS I – which enrolled UC patients who hadn’t previously been treated with anti-TNF drugs, a go-to therapy for the disease.

Unfortunately for Roche, the drug failed to match that performance in a confirmatory trial in the same patient population (HIBISCUS II), and was no better than placebo at maintaining remission in these patients, according to the LAUREL study.

Finally, in the HICKORY trial involving patients previously treated with anti-TNF drugs, the antibody was able to beat placebo at inducing remission, but once again was no better at maintaining that response.

With one and a half positive results out for four from the phase 3 programme, the future of etrolizumab in UC looks in doubt, although Roche is still testing the drug in a pivotal study in Crohn’s disease, another form of IBD, with and without prior anti-TNF treatment.

Roche’s chief medical officer Levi Garraway said the company is “analysing these data to learn more about how we might address the needs of people with this devastating disease.”

There’s no hiding that the data is a big setback for Roche as it goes after Entyvio (vedolizumab), another integrin-targeting antibody that has become a go-to treatment for UC after besting AbbVie’s TNF drug Humira (adalimumab) in the VARSITY head-to-head study. Takeda reported sales of more than 101 billion yen ($945 million) for its drug in the three months ended 30 June.

Entyvio targets the alpha-4 beta-7 integrin, and Roche had gambled that blocking a second target (alpha-E beta-7 integrin) with etrolizumab would improve its efficacy.

As it stands, the biggest challenger to Takeda’s drug is now Johnson & Johnson’s IL-2/IL-23 inhibitor Stelara (ustekinumab), which was approved for UC last year and according to market research firm Spherix has had a strong roll-out in the new indication.

Also heading through the UC pipeline are oral JAK inhibitors from Gilead and AbbVie, oral S1P inhibitors from Bristol-Myers Squibb and Arena, and new biologics including selective IL-23 inhibitors from AbbVie, J&J and Eli Lilly.

Roche has often also been listed as a key challenger in what looks set to become an increasingly challenging and competitive UC market in the coming years, particularly as the drug is administered as a once monthly subcutaneous injection rather than intravenously. Now, that looks much less likely.