Astra could be fashionably late with benralizumab
AstraZeneca is late to the party again with its anti-interleukin-5 antibody benralizumab, with the project nearly two years behind GlaxoSmithKline’s Nucala. But this time Astra might benefit from a best-in-class product, Bryan Garnier analysts believe, based on results presented at the weekend at the European Respiratory Society meeting.
Nucala’s 2022 sales forecast is more than double that for benralizumab, according to EvaluatePharma sellside consensus (see table below). But this could change as analysts start to take the latest data into account. Also in Astra’s favour is the fact that Glaxo has had to create the market for IL-5-targeting antibodies, with Nucala reporting revenues of just £14m ($18.7m) in the second quarter.
One reason that sales have been slow to build is that the drugs, which aim to reduce eosinophil levels, are only used in severely ill patients whose asthma has not responded to other therapies. 315 million people are affected by asthma, Astra estimates, but only 10% have severe disease, and of these only around 40% are uncontrolled on current medications.
Being late to the market therefore might not be such a bad thing, with Astra able to take advantage of Glaxo’s efforts to raise awareness of this drug class. Astra plans to file benralizumab in the US and Europe this year, with approval expected in 2017.
|Anti-interleukin-5 MAbs for asthma|
|Product||Company||Status||2022e sales ($m)|
|Cinqair||Teva Pharmaceutical Industries||Marketed||453|
|Long-acting IL-5 MAb||GlaxoSmithKline||Preclinical||–|
The two phase III studies presented at the ERS, Calima and Sirocco, found that benralizumab reduced the annual rate of asthma exacerbations by up to 51%, similar to results seen with Nucala. However, while Sirocco found a 45-51% reduction in exacerbations versus placebo, Calima showed a less impressive 28-36% decrease due to a strong placebo response.
Meanwhile, Astra’s project appears to be better at improving lung function, with a change in FEV1 of around 150-160ml versus 130-140ml with subcutaneous Nucala. Benralizumab targets the IL-5 receptor, while Nucala and Teva's Cinqair act on the molecule itself.
It is obviously not ideal to compare results across trials, but Astra will be looking for anything that might give it an edge. The company could also pursue a more convenient eight-week dosing schedule, compared with every four weeks for Nucala, as data with benralizumab were similar with both regimens.
It is unclear whether this schedule would also mean a lower price. If benralizumab is cheaper Astra could gain market share in an increasingly cost-conscious healthcare sector.
But benralizumab will not only be going up against Nucala; the interleukin-targeting field is getting increasingly crowded, with the next-biggest threat probably Sanofi/Regeneron’s anti-IL-4 and IL-13 MAb dupilumab, in phase III.
This drug is expected to bring in $837m in asthma by 2022, according to EvaluatePharma consensus forecasts – but its bigger opportunity is dermatitis, where it is expected to make $1.3bn the same year.
Astra has its own anti-IL-13-MAb, tralokinumab, also in phase III in asthma. It will be hoping that Roche’s setback with the similarly-acting lebrikizumab does not represent a class effect (Roche’s asthma stumble gives Glaxo the upper hand, February 29, 2016).
|AstraZeneca’s top five pipeline assets|
|Project||Status||Therapy area||Mechanism||2022e sales ($m)|
|Durvalumab||Phase III||Oncology||Anti PD-L1 MAb||1,673|
|Acalabrutinib||Phase III||Oncology||BTK inhibitor||916|
|Tremelimumab||Phase III||Oncology||CTLA4 MAb||668|
|Benralizumab||Phase III||Asthma||Anti-IL-5 MAb||577|
Benralizumab is far from Astra’s most valuable pipeline asset: that honour goes to durvalumab, another laggard that looks likely to become the fourth or fifth anti-PD-1/PD-L1 oncology drug to reach the market.
But the positive asthma findings will still be a boost for the company as it attempts to turn its highly valued pipeline – a cornerstone of its rejection of Pfizer’s takeover bid – into actual sales.