AstraZeneca’s Benralizumab Asthma Chase Gets Underway
Executive Summary
Watch out GlaxoSmithKline and Teva: AstraZeneca's benralizumab has wind in its sails following a EU CHMP positive opinion for severe asthma. Approval in the US is also expected by year end.
AstraZeneca PLC is set to give chase to GlaxoSmithKline PLC's Nucala (mepolizumab) and Teva Pharmaceutical Industries Ltd.'s Cinqair (respizumab) in the severe eosinophilic asthma market, with a positive approval opinion from the European Medicines Agency's CHMP for its monoclonal antibody product benralizumab (as Fasenra) at its latest meeting this week.
The go-ahead covers benralizumab's use as an add-on maintenance treatment in adult patients with severe eosinophilic asthma inadequately controlled despite high-dose inhaled corticosteroids plus long acting β agonists. A similar approval in the US is also expected by the end of the year.
At its third quarter results presentation on Nov. 9, AstraZeneca emphasized an expected return to sales growth in 2018 driven largely by its cancer portfolio, in particular, Lynparza (olaparib), Tagrisso (osimertinib), Imfinzi in stage III NSCLC, plus its new mantle cell lymphoma therapy Claquence (acalabrutinib).
But respiratory is still an important area for new products for AstraZeneca as it weathers generic competition to its blockbusters, Symbicort (budesonide/formoterol) and Pulmicort (budesonide). As well as benralizumab, it is also developing what it hopes will be a game-changer in severe asthma, the first-in-class injectable anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody tezepelumab. However, another product hopeful, the anti-IL13 human monoclonal antibody tralokinumab, looks set to be dropped after a further Phase III failure in severe uncontrolled asthma. (Also see "End Of The Line For AstraZeneca’s Tralokinumab In Asthma" - Scrip, 1 Nov, 2017.) Analysts at Leerink forecast sales of AZ's respiratory biologicals at $870m in 2022.
Once launched, AstraZeneca is confident that benralizumab will quickly be able to catch up its more established competitors. It cites its differentiated mechanism of action plus its more favorable dosing regimen as factors that will make the product more attractive to doctors and patients.
Benralizumab binds directly to the IL-5α receptor on an eosinophil and uniquely attracts natural killer cells to induce apoptosis. If approved, benralizumab will be available as a once every eight week fixed-dose subcutaneous injection via a prefilled syringe.
By comparison, Cinqair (which was approved in 2015) and Nucala (which was approved last year) target the IL-5 ligand.
Analysts at Datamonitor Healthcare expect benralizumab to see the greatest uptake of all the marketed and late-phase biologics being developed for the treatment of asthma. "While the lack of direct head-to-head trials with these biologics makes comparison of efficacy and safety challenging, pulmonologists suggest that benralizumab’s mechanism of action results in a faster onset of action, giving the drug a competitive advantage."
Added to which is benralizumab's more convenient dosing schedule than Cinqair and Nucala, which boosts its overall clinical attractiveness. "As with other biologics for asthma, benralizumab’s overall uptake will be limited to a small subset of patients who are inadequately controlled on available therapies, but its high expected price point will mean high returns," the Datamonitor analysts said.
Nucala is dosed subcutaneously every four weeks, while Cinqair is dosed intravenously every four weeks.
Winds Of Change
The CHMP recommendation is based on results from the WINDWARD clinical trial program, which included the pivotal Phase III exacerbation trials, SIROCCO and CALIMA, and Phase III oral corticosteroid-sparing trial, ZONDA. (Also see "Why AZ Respiratory Head Believes Third-Placed Benralizumab Can Conquer Market" - Scrip, 7 Sep, 2016.)
AstraZeneca said that a recent pooled analysis of the SIROCCO and CALIMA trials identified specific, well-defined characteristics of an eosinophilic phenotype that will allow clinicians to more precisely select the severe asthma patients most likely to receive maximum benefit from treatment with benralizumab.