AstraZeneca ends leukaemia trial early after promising results

AstraZeneca has said that it will stop a Phase III trial of its chronic lymphocytic leukaemia drug Calquence (acalabrutinib) early after the drug met its primary endpoint in an interim analysis.

The company said that in previously-treated patients the drug significantly increased progression-free survival compared to a combination regimen of rituximab plus physician’s choice of idelalisib or bendamustine.

In addition, the safety and tolerability of Calquence was consistent with the known profile.

“Calquence is the first BTK inhibitor to show benefit in a Phase III trial as a monotherapy compared to current standard-of-care combinations used in relapsed or refractory chronic lymphocytic leukaemia,” said AstraZeneca’s executive vice president, R&D oncology José Baselga. “We look forward to presenting detailed results at a forthcoming medical meeting.”

Calquence is also being trialed in treatment-naïve, front-line chronic lymphocytic leukaemia (CLL) in the ELEVATE-TN trial, also expected to read out in 2019.

The drug is currently approved for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) in the US, and is being investigated in other blood cancers in a total of 26 trials.

Calquence, which is co-developed with Acerta Pharma, competes with AbbVie and Janssen’s blockbuster Imbruvica, another Bruton tyrosine kinase (BTK). Analysts have predicted Imbruvica could hit $9.56 billion in sales in 2024.

AstraZeneca quoted potential peak sales of around $5 billion when it acquired the molecule in 2015, though many analyst forecasts are much lower. In any case, an approval in CLL will open up the drug to a much larger market.

The company is mostly pinning hopes on the fact that around 20-30% of patients stop taking Imbruvica because of tolerability issues – these include diarrhoea, bruising, skin discolouration and atrial fibrillation, with adverse events much less common in AZ’s trials.

Calquence’s ability to treat patients who don’t respond to Imbruvica secured it an FDA Breakthrough Therapy Designation for MCL, and then an exceptionally fast approval time of less than three months.

However it could soon see more competition from China-based BeiGene’s zanubrutinib, another BTK inhibitor with a similar safety profile.