Ibrutinib

AstraZeneca’s Calquence became the first BTK inhibitor approved in the US for first-line use in mantle cell lymphoma on Thursday. The drug may now be used in combination with chemoimmunotherapy in adults who can’t be treated with autologous hematopoietic stem cell transplantation. The FDA granted the accelerated approval based on the 27% benefit over placebo on progression-free survival Calquence demonstrated in the Phase 3 ECHO trial last June . This means AstraZeneca can immediately start to capitalize on the lead it has over its nearest rival, BeiGene, whose BTK inhibitor Brukinsa, is still in Phase 3 in first-line MCL. However, there is still a question mark over ECHO’s overall survival endpoint. Data here are not yet mature and findings with Johnson & Johnson and AbbVie’s first-gen BTK, Imbruvica, set a tricky precedent. Imbruvica achieved a median PFS benefit of nearly 28 months in its Phase 3 first-line MCL trial, more than the nearly 17 months the second-gen Calquence showed in ECHO. But Imbruvica’s PFS success did not translate into an improvement in OS, and Imbruvica was not approved for first-line disease. More drastically, in April 2023 J&J withdrew the drug from the US market in the second line setting. It is not clear when full OS data from Calquence’s trial might emerge, though the earlier ECHO data showed a positive trend on this endpoint. PFS data from the Phase 3 trial of Brukinsa in first-line MCL will likely not appear for another couple of years. The study is testing BeiGene’s BTK in combination with Rituxan versus a bendamustine-Rituxan combo. Calquence obtained accelerated US approval in second-line MCL in 2017; on Thursday this was converted into full approval.

A blockbuster AstraZeneca drug may now be used as an earlier treatment for mantle cell lymphoma, making it the first in its class approved as a first-line therapy for this rare and aggressive type of blood cancer. The FDA expanded approval of the drug, acalabrutinib, to include previously untreated MCL in adults who are also ineligible for a hematopoietic stem cell transplant that is a treatment option for younger patients. As a first-line therapy, the AstraZeneca drug must be used in combination with bendamustine and rituximab, a drug regimen often used for older MCL patients. The late Thursday regulatory decision also grants traditional approval to the drug as a single-agent treatment for adults whose MCL has received an earlier line of therapy. MCL is type of B cell non-Hodgkin lymphoma, a cancer of the lymphatic system. Chemotherapy is the standard treatment, but relapse is common. Acalabrutinib, marketed under the brand name Calquence, is a small molecule designed to block Bruton’s tyrosine kinase (BTK), an enzyme that promotes the proliferation and survival of malignant B cells. Healthcare Using Data to Help Healthcare Practices Succeed A new report from Relatient, A Data-Driven Guide to Patient Access Succes, highlights how focusing on data accuracy and relevance can enhance the performance of healthcare practices. By Relatient Calquence, a twice-daily pill, initially won accelerated FDA approval in 2017 as a treatment for adults whose MCL has received at least one prior therapy. In 2019, the AstraZeneca drug’s label expanded to include chronic lymphocytic leukemia or small lymphocytic leukemia. Calquence is one of AstraZeneca’s top oncology products, accounting for $2.5 billion in revenue in 2023, up 25% from the prior year. The latest FDA approval for Calquence is based on the results of ECHO, a Phase 3 study that enrolled 598 patients age 65 and older with untreated MCL. These participants were randomly assigned to receive the study drug plus the bendamustine/rituximab regimen, or a placebo and bendamustine/rituximab. At a median follow-up of 49.8 months, clinical trial results showed longer progression-free survival that was statistically significant. Median progression-free survival was 66.4 months in the study drug arm versus 49.6 months in the comparator group. The Phase 3 data were presented last June during the annual meeting of the European Hematology Association in Madrid. “Managing this aggressive cancer requires maximizing efficacy while maintaining tolerability, especially for elderly patients,” Michael Wang, director of the Mantle Cell Lymphoma Program of Excellence at MD Anderson Cancer Center and principal investigator in the trial, said in a prepared statement included in AstraZeneca’s approval announcement. “Results from the pivotal ECHO trial highlight the promise of the acalabrutinib combination in defining a new standard of care, with today’s approval underscoring the transformative potential of this regimen as a first-line treatment for older patients with mantle cell lymphoma.” presented by Health IT Transforming Patient Care: The Role of AI-Powered Assistants The progress in artificial intelligence (AI) is reshaping patient care, across various dimensions, from facilitating faster discharge to curating treatment plans and suggesting lifestyle changes. By IT Medical Calquence’s new FDA approval makes it the first BTK inhibitor approved as a first-line MCL treatment. That gives the drug an edge over others in its class. Eli Lilly’s BTK inhibitor, Jaypirca, landed FDA approval in 2023 as a third-line treatment for MCL. Imbruvica, marketed by Johnson & Johnson and AbbVie, and Brukinsa, from BeiGene (which is changing its name to BeOne Medicines), are both approved as second-line treatments for MCL.