Before the end of the year Amgen will see data from three key late-stage programmes – sotorasib in NSCLC, omecamtiv in heart failure and the asthma project tezepelumab. While Astrazeneca will see a share of the profits, tezepelumab is a valuable pipeline project for Amgen − blockbuster numbers are expected by 2026, EvaluatePharma consensus suggests.
Tezepelumab is being evaluated in the phase III Navigator study in severe asthma. The market is crowded by biologicals, but Amgen and Astra are targeting a specific type of disease, non-eosinophilic, that has few treatment options.
|% of market cap||2%||1%|
|Event||Phase III data|
The novel monoclonal antibody has a chequered past, having recently failed in a phase II trial in atopic dermatitis, after flunking in the same indication in 2017. This might not bode well for the asthma trial, given the diseases' similar mechanisms; however, Amgen maintained on its second-quarter earnings call that the result in atopic dermatitis had limited read-through to Navigator.
The company added that the best insights into how tezepelumab might perform in asthma would come from its large phase II asthma study. That trial, Pathway, was a success.
It tested tezepelumab as an add-on to corticosteroids or LABAs, and found a reduction in annual asthma exacerbations of 62-71% with three doses of subcutaneous tezepelumab, all of which were significant versus placebo. The reductions were similar in patients with baseline eosinophil counts above and below 250/µl.
Eosinophilia, high levels of white blood cells, is present in approximately 50% of severe asthma cases. Most monoclonal antibodies, including Sanofi’s Dupixent, the expected market leader by 2026, Astra’s Fasenra and Glaxosmithkline’s Nucala, primarily target the eosinophilic phenotype.
Non-eosinophilic disease is just as common but is poorly understood.
Amgen and Astra hope to find a place for tezepelumab by demonstrating its efficacy in severe uncontrolled asthma irrespective of baseline eosinophil counts. The Navigator trial is in 1,061 patients with severe disease inadequately controlled despite treatment with inhaled corticosteroid plus one additional asthma controller medicine. The primary endpoint is annualised asthma exacerbation rate.
Safety will also be closely watched, given that tezepelumab is a novel agent. It targets thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine. There have been concerns that inhibiting the action of TSLP could raise the risk of infections as the cytokine is thought to play a role in host defence against infection.
In Pathway the safety data looked relatively clean, though there were three serious drug-related adverse events that could have been the result of impaired host defence: pneumonia and stroke in the same patient, and Guillain-Barré syndrome in another.
|Biologicals in asthma|
|Product||Company||Description||2020 ($m)||2026e ($m)||Status||Asthma setting|
|Dupixent||Sanofi||Anti-IL-13 and IL-4 MAb||697||2,314||Marketed||Moderate to severe eosinophilic|
|Xolair||Roche/Novartis||Immunoglobulin E regulator||3,306||2,218||Marketed||Severe allergic asthma|
|Fasenra||Astrazeneca||Anti-IL-5 MAb||994||2,014||Marketed||Severe eosinophilic|
|Nucala||Glaxosmithkline||Anti-IL-5 MAb||1,205||1,666||Marketed||Severe eosinophilic|
|Tezepelumab||Amgen/Astrazeneca||Anti-thymic stromal lymphopoietin MAb||-||1,021||Phase III||Severe asthma without eosinophilic phenotype|
|Sources: EvaluatePharma, product labels.|
The only other anti-TSLP MAb in development is Novartis’s inhaled CSJ117, due to start phase II soon. GSK and Roche both had projects in early development, but these now seem to be abandoned, according to EvaluatePharma data.
While Astra leads the development of tezepelumab, the project is one of five antibodies covered by a deal that Astra struck with Amgen back in 2012 for $50m up front. Astra will see a share of the profits.
Tezepelumab is forecast to become Amgen's fourth-biggest growth driver, according to EvaluatePharma sellside consensus, and a setback would leave a rather large hole in the company's pipeline.