FDA approves the first all-oral, fixed-duration therapy for patients with newly diagnosed chronic lymphocytic leukemia

The U.S. Food and Drug Administration (FDA) has approved the combination of AstraZeneca’s Calquence (acalabrutinib) and AbbVie and Roche’s Venclexta (venetoclax) as the first all-oral, fixed-duration regimen for patients with newly diagnosed chronic lymphocytic leukemia (CLL) in the United States.

The regulatory decision is based on results from a clinical trial involving adult patients without del(17p) or TP53 mutations. Data show that the dual therapy reduces the risk of disease progression or death by 35% compared to standard chemoimmunotherapy. Three years after starting treatment, 77% of patients in the experimental group remained progression-free, compared to 67% in the control group.

The new regimen is administered for a fixed period of 14 months, distinguishing it from previous targeted therapies that require administration until disease progression. This creates an opportunity for treatment breaks and potentially limits the accumulation of long-term adverse reactions and the development of drug resistance. Previously, Calquence was authorized for first-line use in combination with chemoimmunotherapy based on the ECHO study, but without a fixed duration.

The approval comes amid intensified competition in the BTK inhibitor segment. BeOne’s Brukinsa (zanubrutinib) has reported significant sales growth following its first-line authorization in 2023, and Eli Lilly’s Jaypirca (pirtobrutinib) recently achieved positive Phase 3 results. Both products show superiority over the older BTK inhibitor Imbruvica (ibrutinib), while Calquence demonstrated equivalent efficacy in a head-to-head comparative study.

The Calquence/Venclexta combination is already approved in the European Union, Canada, and the United Kingdom. The new indication contributed to a 12% growth in Calquence sales to $3.5 billion over the past year, while Venclexta reported an 8% increase to nearly $2.8 billion. Meanwhile, BeOne is conducting late-phase trials of Brukinsa in combination with its own BCL-2 inhibitor, sonrotoclax, in previously untreated CLL patients.