AstraZeneca’s supplemental New Drug Application (sNDA) for Calquence (acalabrutinib) has been accepted for Priority Review by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL). This designation is granted to drugs that could offer significant improvements over existing treatments, particularly in terms of safety, efficacy, or the prevention of serious conditions. The FDA is expected to make its decision by the first quarter of 2025, under the Prescription Drug User Fee Act timeline.
MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL) caused by the mutation of B-lymphocytes in the mantle zone of the lymph node. The disease is often diagnosed at advanced stages and remains largely incurable. Approximately 27,500 people globally are affected by MCL.
Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, highlighted the potential of Calquence to improve outcomes for untreated MCL patients, citing data from the ECHO trial. The study showed that Calquence, when combined with chemoimmunotherapy, significantly delayed disease progression and suggested an improvement in survival for patients facing this currently incurable blood cancer. AstraZeneca is working closely with the FDA to make this new treatment available to patients as soon as possible.
The sNDA is also being reviewed under Project Orbis, an FDA initiative that facilitates the simultaneous review of cancer drugs by international regulatory agencies, aiming to accelerate the availability of cancer treatments globally.
Results from the ECHO Phase III trial, presented at the European Hematology Association (EHA) 2024 Hybrid Congress, showed that the combination of Calquence, bendamustine, and rituximab reduced the risk of disease progression or death by 27% compared to standard chemoimmunotherapy (hazard ratio [HR] 0.73; p=0.016). Patients treated with the Calquence combination experienced a median progression-free survival (mPFS) of 66.4 months, nearly 1.5 years longer than those receiving standard care, who had an mPFS of 49.6 months.
Although overall survival (OS) data favored the Calquence combination, the results were not yet statistically significant (HR 0.86; p=0.2743) at the time of this analysis, partly because many patients in the standard-of-care arm switched to BTK inhibitors like Calquence after their initial treatment. The OS data remain immature, and the trial will continue monitoring survival outcomes as a key secondary endpoint.
The ECHO trial took place during the COVID-19 pandemic, so the study included prespecified analyses to account for COVID-19-related deaths. These adjusted analyses showed an even greater improvement in PFS for the Calquence combination, with a 36% reduction in the risk of disease progression or death (HR 0.64; p=0.0017). OS trends were also favorable, although the data were still not fully mature (HR 0.75; p=0.0797).
Calquence’s safety profile remained consistent with previous findings, with no new safety concerns identified.
Background on Mantle Cell Lymphoma (MCL):
MCL is a challenging disease because patients often relapse despite responding initially to treatment. It accounts for about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 people in Western countries. In the U.S., around 4,000 new cases of MCL are diagnosed each year.
ECHO Trial Overview:
The ECHO trial is a Phase III, double-blind, placebo-controlled study that included 635 adult patients aged 65 or older with previously untreated MCL. Patients were randomly assigned to receive either Calquence or a placebo in addition to standard chemoimmunotherapy (bendamustine and rituximab). The trial’s primary goal was to evaluate progression-free survival, while other objectives included overall survival, response rates, and time to response. The study was conducted across 27 countries and spanned from May 2017 to March 2023, during the COVID-19 pandemic.
About Calquence:
Calquence (acalabrutinib) is a second-generation Bruton’s tyrosine kinase (BTK) inhibitor that blocks B-cell signaling pathways involved in cell growth and survival. It has been used to treat over 85,000 patients worldwide and is currently approved for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in the U.S., EU, and other regions. Calquence is also approved for previously treated MCL in several countries, though it is not yet approved for MCL in Japan or the EU.
AstraZeneca continues to evaluate Calquence in clinical trials, both as a standalone treatment and in combination with other therapies, for various B-cell blood cancers, including MCL and diffuse large B-cell lymphoma.
AstraZeneca in Oncology and Hematology:
AstraZeneca is committed to revolutionizing cancer care by developing innovative treatments for some of the most difficult-to-treat cancers. Through its acquisitions of Alexion and Gracell Biotechnologies, AstraZeneca has expanded its capabilities in both malignant and non-malignant blood disorders, aiming to transform care for patients worldwide.
