Roche breathes easier with positive data for severe asthma drug

Positive phase II data for Roche’s antibody lebrikizumab should help it get closer to even footing in the race to market a new drug for severe asthma.

Phase III trial results are expected soon for Teva’s Cinquil and GlaxoSmithKline’s mepolizumab, both of which have seen slow progress in treating uncontrolled asthma driven by overproduction of eosinophils. Roche’s own phase III programme is well under way, but it needs to differentiate itself in a space that could get very congested as numerous drugmakers target this population (Therapeutic focus – Interleukin modulators crowd pipeline for severe asthma, May 28, 2013).

A little help from a friend

Roche outlined results from the Lute and Verse trials at the AAAAI meeting in San Diego; both studies had been filed as phase III but converted to phase II because of manufacturing deficiencies.

Pooled data from the two trials in 463 patients showed reductions in asthma attacks in all treated patients versus placebo, and this effect was driven by those with high blood levels of periostin, a biomarker for elevated eosinophils. The exacerbation rate versus placebo was 60% for periostin-high patients and only 5% in those with low periostin.

The lack of a dose response might be one concern, however: patients were given lebrikizumab doses of 37.5mg, 125mg and 250mg, and reported exacerbation rates of 62%, 35% and 11% respectively, though confidence bands were wide. All patients enrolled were unable to control their asthma on a regimen of inhaled corticosteroids and at least one other type of medication.

Roche’s Cobas diagnostic division has developed a companion test to identify those patients who are likely to respond because of elevated periostin – the company says that biomarker is a specific indicator that interleukin-13 (IL-13) is a major contributor to airway inflammation. With this personalised medicine approach, Roche hopes to have a stronger efficacy case to present to regulators when it submits lebrikizumab for approval, not to mention justifying its likely higher cost to payers as the eligible patient population could be more easily identified.

EvaluatePharma’s consensus forecasts $73m in sales in 2018. Analysts from Bryan Garnier this morning said they expected first sales to come in 2018, totalling SFr158m ($178m) that year.

Stumbles

The companion diagnostic is one potential differentiator for lebrikizumab. The other is its target – IL-13 rather than IL-5 in the case of Cinquil and mepolizumab. Those two agents should be approaching their phase III readouts imminiently, although Teva and Glaxo have said little about the trials.

While Roche might rue having had to downgrade its phase III programme for lebrikizumab, the clinical paths of the leading eosinophilic asthma products have not exactly been straightforward.

Mepolizumab, as Bosatria, had once been submitted in Europe for hypereosinophilic syndrome but was withdrawn as rejection had looked certain. Cinquil, which came with Teva’s 2011 acquisition of Cephalon, has not exactly fitted the Israeli speciality/generics group’s pipeline and cannot have been a management focus as executives tried to address the immediate issues presented by the looming expiry of Copaxone’s patent and stalling sales growth.

In the meantime, the late-stage pipeline of interleukin-targeting antibodies has got a bit more busy: AstraZeneca advanced benralizumab into phase III late last year, while Novartis, Astra, Sanofi and Amgen could all report phase II data by the end of this year. Significantly, the nearest IL-13 is Astra’s tralokinumab (CAT-354), which could report phase IIb data in mid to late-2014.

With its first phase III data out in 2016 Roche is not out of the uncontrolled asthma game by a long shot. It will probably have serious competition – clear differentiation and sharp elbows in the marketing game will help its chances.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter