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With new data, AstraZeneca makes the case for its BTK inhibitor in a first-line setting

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Combined with chemotherapy and immunotherapy, AstraZeneca’s Calquence reduced the risk of disease progression or death by 27% compared to placebo and chemoimmunotherapy in first-line mantle cell lymphoma.

Last month, the company shared topline data from the ECHO Phase 3 trial. And over the weekend it laid out more detailed results for its blockbuster BTK inhibitor at the European Hematology Association’s annual meeting.

If Calquence gets an expanded label in this indication, it would be the only BTK inhibitor approved in the first-line setting.

Along with reducing the risk of disease progression or death, AstraZeneca said median progression-free survival was 66.4 months for patients treated with the Calquence combination versus 49.6 months with chemoimmunotherapy, the current standard of care. The secondary endpoint of overall survival showed a trend in favor of Calquence, but wasn’t mature at the time of the analysis.

AstraZeneca also did an analysis on the trial that factored in deaths related to Covid-19, since it enrolled during the pandemic. When accounting for the impact of Covid, the data are better: Progression-free survival improved in both the Calquence and placebo arms. Calquence reduced the risk of disease progression or death by 36%, and there was a favorable trend for overall survival.

Benjamin Moutier, AstraZeneca’s head of its global hematology franchise, told Endpoints News that the Calquence combo could become the new standard of care and that the company will work with regulatory authorities to make the combo available “as soon as possible.”

“There is a very high unmet need in first-line MCL,” Moutier said. “We see very strong improvement in terms of progression-free survival — nearly one and a half years of progression. We see a trend in terms of overall survival, which is the first time that a BTKi has demonstrated an OS trend.”

Calquence, which brought in $2.5 billion in sales last year, was acquired by AstraZeneca in 2015 when it paid $7 billion to buy a majority stake in Acerta Pharma. It was first approved in the second-line setting for relapsed/refractory mantle cell lymphoma in 2017, competing with AbbVie and J&J’s Imbruvica. It has scored other approvals, including as a monotherapy and as a combination treatment for chronic lymphocytic leukemia and small lymphocytic lymphoma.

Other BTK inhibitors like BeiGene’s Brukinsa and Eli Lilly’s Jaypirca are also used to treat patients with mantle cell lymphoma.


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