In next-gen BTK battle, AbbVie and J&J tout pivotal data backing Imbruvica as a combo treatment
Last week, AstraZeneca took a swing at J&J and AbbVie’s first-generation BTK inhibitor Imbruvica in the blood cancer chronic lymphocytic leukemia with long-term data from a head-to-head trial. But the partners aren’t going down without a fight.
AbbVie and Janssen unveiled pivotal data on Saturday showing that first-line CLL patients who received Imbruvica and AbbVie’s Roche-partnered Venclexta lived longer without disease progression than patients on Gazyva and the chemotherapy chlorambucil. The Phase III GLOW trial enrolled 211 elderly patients, or those with comorbidities or concurrent illnesses. Overall, the median age was 71 years old.
Median progression-free survival wasn’t reached in the Imbruvica arm compared with 21 months in the Gazyva arm — showing a 78% reduction in the risk of disease progression or death, the partners said.
At three months post-treatment, undetectable minimal residual disease was 51.9% in the bone marrow of Imbruvica patients compared to 17.1% in the Gazyva arm (p<0.0001), and 54.7% versus 39% in the peripheral blood (p<0.0001). Undetectable minimal residual disease in the peripheral blood was sustained by 85% of patients one year post-treatment in the Imbruvica arm, according to the data.
At the time of assessment, 38.7% of Imbruvica patients saw complete responses (including those with incomplete hematologic recovery), versus 11.4% of patients on Gazyva and chlorambucil (p<0.0001).
“The data from GLOW showed that ibrutinib in an oral, once-daily fixed-duration combination with venetoclax outperformed a standard chemoimmunotherapy regimen for older or unfit patients, providing the first comparative evidence that this approach has the potential to improve depth of response and, therefore, extends time to progression versus standard therapy,” the study’s principal investigator Arnon Kater said in a statement.
Imbruvica inhibits BTK, an enzyme that plays a crucial role in oncogenic signaling that’s key for the proliferation and survival of leukemic cells in many B-cell malignancies. The blockbuster drug was first approved in 2013, but safety and tolerability issues soon emerged. Since then, second-generation candidates like AstraZeneca’s Calquence have been positioned as safer but equally effective alternatives.
At #ASCO21, AstraZeneca unveiled long-term data that showed Calquence matched Imbruvica for a median PFS of 40.9 months in CLL patients, but bested Imbruvica when it came to occurrence of cardiac events. Incidence of all-grade atrial fibrillation — an irregular heartbeat that can lead to stroke or heart failure — was 9.4% in the Calquence arm, compared to a 16% rate in the Imbruvica arm (p=0.02).
Last week, BeiGene read out interim results from a Phase III study comparing its own BTK inhibitor Brukinsa to Imbruvica in patients with relapsed/refractory CLL or small lymphocytic lymphoma (the same disease as CLL but in the lymph nodes). An independent review committee reported that the overall response in the Brukinsa arm was numerically higher but not statistically significant. However, there was a statistically significant lower risk of atrial fibrillation or flutter.
In the GLOW study, AbbVie and Janssen said the safety profile of Imbruvica and Venclexta was “consistent with CLL treatment in an older population with comorbidities.” Seven patients died during treatment in the Imbruvica arm, compared to two deaths in the Gazyva arm.