AstraZeneca's Calquence Triumphs Early in First-Line MCL as Imbruvica Exits

AstraZeneca's Calquence has achieved a significant milestone in the treatment of previously untreated mantle cell lymphoma (MCL), becoming the first BTK inhibitor to show an early overall survival benefit in this patient population. This was highlighted by AstraZeneca’s oncology research and development chief, Susan Galbraith, Ph.D., who pointed out the drug's unique early survival signal and its distinctive safety profile.

Calquence, when used in combination with bendamustine and rituximab (BR), demonstrated a significant delay in cancer progression or death compared to standard chemoimmunotherapy alone in newly diagnosed MCL patients. This promising result comes from an interim analysis of the phase 3 ECHO trial, which AstraZeneca had initially anticipated to read out in 2025. The data from this trial could potentially lead to converting Calquence's current accelerated approval for previously treated MCL into full approval. However, there is uncertainty about whether AstraZeneca can proceed with an immediate FDA filing, given the precedent set by Imbruvica's previous challenges.

The ECHO trial results arrived earlier than expected, with the primary endpoint of progression-free survival being met. Despite the positive early findings, AstraZeneca acknowledged that the overall survival data was not yet mature at the time of interim analysis. The study will continue to monitor this critical secondary endpoint. An AstraZeneca spokesperson confirmed that the data will be shared with health authorities and that the trial is ongoing.

This development comes after AbbVie and Johnson & Johnson withdrew Imbruvica's accelerated approval for previously treated MCL and marginal zone lymphoma last year. Imbruvica faced setbacks due to its overall survival data in MCL. In the phase 3 SHINE study, Imbruvica combined with BR significantly reduced the risk of disease progression or death by 25% compared to BR alone. However, overall survival rates between the two groups were comparable, with a slight increase in the risk of death linked to Imbruvica.

While Imbruvica's exit from the market has opened new opportunities, Calquence may still face future competition from BeiGene’s Brukinsa. Brukinsa, which also has FDA accelerated approval for previously treated MCL, is currently being evaluated in combination with rituximab versus the BR combo in untreated MCL in the phase 3 BGB-3111-306 trial. This trial completed recruitment at the beginning of 2024 and has a primary completion date set for March 2027.

Calquence and Brukinsa are now in direct competition, especially with Imbruvica losing favor among doctors due to safety concerns. In 2023, BeiGene reported $1.3 billion in global sales for Brukinsa, a 129% increase from the previous year. During the same period, Calquence generated $2.5 billion in sales for AstraZeneca, marking a 22% increase.

In the crucial first-line chronic lymphocytic leukemia (CLL) market, Calquence remains the leading BTK inhibitor in the U.S. and Europe. Recently, AstraZeneca announced results from the phase 3 ChangE trial in Asia, showing that Calquence monotherapy outperformed the combination of chlorambucil and rituximab in progression-free survival for untreated CLL patients. Additionally, the phase 3 AMPLIFY trial is exploring Calquence in combination with AbbVie and Roche’s BCL2 inhibitor Venclexta, with or without Roche’s anti-CD20 antibody Gazyva, in first-line CLL. Similarly, BeiGene is assessing Brukinsa in combination with its second-generation BCL2 inhibitor sonrotoclax in CLL.