FDA Grants Priority Review to Calquence for Untreated Mantle Cell Lymphoma
核心洞察
The FDA granted Priority Review to AstraZeneca's Calquence (acalabrutinib) for untreated mantle cell lymphoma (搜索) (MCL (搜索)), expediting its potential approval.
The decision is based on the Phase III ECHO trial, which showed Calquence plus chemoimmunotherapy significantly reduced disease progression risk.
The ECHO trial demonstrated a 27% reduction in disease progression or death compared to standard chemoimmunotherapy in MCL (搜索) patients.
AstraZeneca's supplemental New Drug Application (sNDA) for Calquence (acalabrutinib) has received Priority Review from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with previously untreated mantle cell lymphoma (搜索) (MCL (搜索)). This designation accelerates the review process for drugs that offer significant improvements over existing options.
The FDA's decision is based on data from the Phase III ECHO trial, which evaluated Calquence in combination with bendamustine and rituximab compared to standard chemoimmunotherapy (bendamustine and rituximab) in patients aged 65 years and older with previously untreated MCL (搜索). The Prescription Drug User Fee Act (PDUFA) date, the FDA's action date for their regulatory decision, is anticipated during the first quarter of 2025.
ECHO Trial Results
The ECHO trial demonstrated that Calquence plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy (HR 0.73; 95% CI 0.57-0.94; p=0.016). Patients treated with the Calquence combination experienced a median progression-free survival (mPFS) of 66.4 months, compared to 49.6 months with standard-of-care.
While overall survival (OS) data were not mature at the time of analysis, a favorable trend was observed for the Calquence combination (HR 0.86; 95% CI 0.65-1.13; p=0.2743). It's important to note that most patients in the standard-of-care arm who required subsequent therapy received a BTK (搜索) inhibitor, mainly Calquence.
Impact of COVID-19
The ECHO trial was conducted during the COVID-19 pandemic. Prespecified PFS and OS analyses censoring for COVID-19 deaths were conducted to assess the impact of COVID-19 on the study outcome. After censoring for COVID-19 deaths, the Calquence combination reduced the risk of disease progression or death by 36% (HR 0.64; 95% CI; 0.48-0.84; p=0.0017). A favorable trend was seen for OS in this analysis for the Calquence combination (HR 0.75; 95% CI 0.53-1.04; p=0.0797).
Safety Profile
The safety and tolerability of Calquence in the ECHO trial were consistent with its known safety profile, and no new safety signals were identified. Common adverse events (AEs) of Grade 3 or higher included atrial fibrillation, hypertension, major bleeding, and infections. AEs resulting in treatment discontinuation occurred in 10.4% of patients administered the Calquence combination and 6.4% of patients in the standard-of-care arms.
Expert Commentary
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, stated, “Today’s Priority Review acceptance reinforces the potential of Calquence to transform outcomes in untreated mantle cell lymphoma (搜索). Data from the ECHO trial showed Calquence plus chemoimmunotherapy significantly delayed disease progression and showed a trend to improved survival in patients with this currently incurable blood cancer. We are working closely with the FDA to provide patients this potential new treatment as soon as possible.”
About Mantle Cell Lymphoma
Mantle cell lymphoma (搜索) (MCL (搜索)) is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), resulting when B-lymphocytes mutate into malignant cells within a region of the lymph node known as the mantle zone. It accounts for approximately 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries. In the US, it is estimated that approximately 4,000 new patients are diagnosed with MCL each year. The disease is often diagnosed at advanced stages and remains largely incurable. It is estimated that there are more than 27,500 people living with MCL worldwide.
Project Orbis
The sNDA is being reviewed under Project Orbis, an initiative of the FDA which provides a framework for concurrent submission and review of oncology medicines among participating international partners to bring cancer treatments to patients around the world as early as possible.