The US Food and Drug Administration (FDA) has approved AstraZeneca’s Calquence (acalabrutinib) as a first-line combination therapy for treating patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation.

The US regulatory approved Calquence in combination with chemotherapy, bendamustine, and an anti-CD20 (cluster of differentiation 20) monoclonal antibody, rituximab. The approval was based on the positive data from the Phase III ECHO trial.

The US FDA also expanded the therapy’s label as a second-line treatment for MCL by granting full approval. In October 2017, AstraZeneca received accelerated approval from the US regulatory agency for Calquence as a treatment for adult patients with MLC previously treated with at least one prior therapy.

ECHO Phase III trial data

Calquence is a selective inhibitor of Bruton’s tyrosine kinase (BTK). It covalent binds to BTK and inhibits its activity, which can signal the activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.

The randomized, double-blind, placebo-controlled Phase III ECHO trial (NCT02972840) evaluated the safety and efficacy of the combination therapy of Calquence, bendamustine, and rituximab in 635 adult patients at or over 65 years of age with previously untreated MCL. The combination therapy reduced the risk of disease progression or death by 27%, compared to standard-of-care chemoimmunotherapy (placebo group).

The patient who received a Calquence combination therapy showed a median progression-free survival (PFS) of 66.4 months, compared to the median PFS of 49.6 months seen in the placebo group.

AstraZeneca also reported Covid-19 censored data, as the trial enrolled participants during the pandemic. After censoring Covid-19 related deaths, AstraZeneca noted that PFS was improved across both arms, Calquence combination reducing the risk of disease progression or death by 36%.

The safety profile was comparable across both groups, with 88.9% and 88.2% of participants reporting Grade 3 or higher adverse events (AEs) in the Calquence combination and placebo groups, respectively. Commonly observed AEs were atrial fibrillation, hypertension, major bleeding, and infections. AEs leading to discontinuation were seen in 10.4% of patients for the Calquence combination arm, compared to 6.4% of the placebo arms.

What the approval means for AstraZeneca

AstraZeneca secured the approval as part of the priority review program through the US FDA. The US regulatory agency issues a priority review voucher following the FDA approval “for a drug or biological product for a rare pediatric disease”. The agency issues the vouchers as part of its initiative to incentivize drug development for rare pediatric diseases.

Sponsors who receive these vouchers can redeem or sell them to raise capital. The priority reviews can reduce the FDA review time of a drug application from the usual 10 months to 6 months.

Dave Fredrickson, Executive Vice-President, Oncology Hematology Business Unit, AstraZeneca, said: “With today’s approval, Calquence provides a critical new treatment option to mantle cell lymphoma patients in the US, with Calquence proven to deliver nearly one and a half years of additional time without disease progression.”

Fredrickson also noted that the approval reinforces our belief in Calquence as a backbone therapy across multiple blood cancers.” Apart from approval as a treatment for MCL, the US FDA approved the therapy for treating chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in November 2019.

However, Calquence’s profits may be in jeopardy, as the therapy is included in the list of 15 drugs that are expected to be in the second cycle of Medicare drug negotiations. A factsheet from the Centers for Medicare and Medicaid Services (CMS) noted that about 15,000 Medicare beneficiaries took the therapy between November 2023 and October 2024 at a total cost of $1.6 billion to the Medicare Part D program.