AstraZeneca ends another Calquence trial early

For the second time in the space of a month AstraZeneca has stopped a trial of its chronic lymphocytic leukaemia (CLL) drug Calquence (acalabrutinib) early following positive results.

The company has announced that the phase 3 ELEVATE-TN trial of Calquence in patients with previously-untreated CLL met its primary endpoint, with Calquence in combination with obinutuzumab demonstrating a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) when compared with the chemotherapy-based combination of chlorambucil and obinutuzumab.

The trial also met a key secondary endpoint showing Calquence monotherapy achieved a statistically-significant and clinically-meaningful improvement in PFS compared to the chemotherapy and obinutuzumab regimen.

The safety and tolerability of the drug was consistent with its established profile.

More detailed results will be revealed at a forthcoming medical meeting.

Last month AZ announced it would stop the phase 3 ASCEND trial in previously-treated patients after the drug was shown to significantly increase progression-free survival compared to a combination regimen of rituximab plus physician’s choice of idelalisib or bendamustine.

José Baselga, the company’s executive vice president of oncology R&D, said the positive results from both the ELEVATE-TN and ASCEND trials will serve as the foundation for regulatory submissions later this year.

Calquence 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.