ASH 2024 – AstraZeneca aims to fix Calquence’s position

While BeiGene’s Brukinsa is emerging as the covalent BTK inhibitor of choice in chronic lymphocytic leukaemia, sales of AstraZeneca’s Calquence are still growing. The UK company aims to shore up its position with data being presented at ASH on Monday from the phase 3 Amplify trial, testing a fixed duration of Calquence in first-line CLL.

The study found that Calquence plus the BCL-2 inhibitor Venclexta reduced the risk of disease progression or death by 35% versus chemoimmunotherapy, and a Calquence/Venclexta/Gazyva triplet did even better, with a 58% reduction. However, the bigger question for Astra could be how Calquence compares to Brukinsa, which got the a first-line CLL label last year based on the Sequoia trial.

That’s because in Alpine, a second-line CLL trial that is also an approved Brukinsa setting, the Beigene drug beat Imbruvica head-to-head, while Calquence has only shown non-inferiority to the Abbvie/Johnson & Johnson drug.

And a threat to all the approved BTK inhibitors could be coming from degraders, with projects from BeiGene and Nurix also set to feature at ASH on Monday.

Fixed

Calquence is already approved for first-line CLL, but is currently given until disease progression. Amplify tested a fixed-duration of 14 cycles (each 28 days) which, Astra said, could allow patients to take breaks from therapy, reducing the risk of long-term adverse events and drug resistance.

The company has claimed that Calquence plus Venclexta could become the only medicine in front-line CLL approved for both fixed and extended durations of treatment. Astra hasn’t yet given details of its filing plans here.

But one fly in the ointment could be overall survival. With the caveat that the data are immature, only Calquence plus Venclexta showed a trend towards an OS benefit, which wasn’t seen with Calquence/Venclexta/Gazyva.

Whether the availability of fixed-duration Calquence will boost sales is another question. Still, the drug is doing well for now, with revenues up 26% in the first nine months of 2024, at $2.3bn. During its third-quarter earnings call last month, Astra’s head of oncology R&D, Susan Galbraith, said that doctors preferred finite therapy for around half of patients, including those who are fitter.

The next big events for Calquence will be an approval decision in first-line mantle cell lymphoma early next year, and readout of the phase 3 Escalade trial in DLBCL.

Meanwhile, BeiGene will present data at ASH on Monday from a phase 1 trial combining Brukinsa with its BCL-2 inhibitor sonrotoclax in first-line CLL – the abstract shows an ORR of 100% and a complete response rate of just over 40%. A phase 3 trial has already begun, testing the combo head to head against Venclexta plus Gazyva.

Notable Calquence trials

Source: OncologyPipeline & company presentation.