AbbVie Stock Drops After Disappointing Clinical Trial Update
By Mark Terry
AbbVie updated its Phase III trial of Imbruvica (ibrutinib) in untreated diffuse large B-cell lymphoma (DLBCL), an aggressive type of non-Hodgkin lymphoma (NHL). The trial, DBL3001, studied the addition of Imbruvica to a chemotherapy regimen of five different drugs used in combination—rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) compared to R-CHOP and a placebo. It was conducted in a subset of untreated DLBCL patients that have the non-germinal center B cell (GCB) or activated B-cell (ABC) subtypes. These patients usually have poorer outcomes.
The data found that Imbruvica plus R-Chop was not superior to R-CHOP alone. That means it missed its primary endpoint of improving event-free survival (EFS) in the targeted patient population. But the company is holding out hopes, saying clinically meaningful improvements were seen in a patient subpopulation that they will study more.
AbbVie expects to release full data at an upcoming conference and publish results in a peer-reviewed medical journal.
“Since its first U.S. FDA approval in 2013, Imbruvica has redefined standard of care in many different blood cancers—several of which had little to no treatment options available to patients before,” said Thorsten Graef, head of Clinical Development at Pharmacyclics, an AbbVie company, in a statement. “These medical achievements reflect our objective of focusing research where there is great unmet patient need and understanding that the nature of research is such that some studies succeed and others do not. We continue to believe that ibrutinib has great untapped potential as a cancer treatment alone or in combination. Together with our global partner Janssen, we are advancing our robust ibrutinib scientific development program and anticipate results from several studies in the future.”
There are currently 30 ongoing company-sponsored clinical trials of Imbruvica with 14 in Phase III. There are more than 100 investigator-sponsored trials and external collaborations worldwide.
On June 25, the U.S. Food and Drug Administration (FDA) accepted AbbVie’s supplemental New Drug Application (sNDA) for Imbruvica in combination with Rituxan (rituximab) as a new treatment option for Waldenstrom’s macroglobulinemia (WM), a rare and incurable blood cancer.
Imbruvica works primarily by blocking a protein called Bruton’s tyrosine kinase (BTK), a key signaling molecule in the B-cell receptor signaling complex that is involved in the survival and metastases of malignant B cells. It has been approved in six distinct patient populations so far: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenstrom’s macroglobulinemia, along with previously-treated mantle cell lymphoma (MCL), previously-treated marginal zone lymphoma (MZL) and previously-treated chronic graft-versus-host disease (cGVHD).
“We are excited about the data from the Phase III iNNOVATE study, which indicate that Imbruvica plus rituximab was able to improve progression-free survival, versus rituximab alone, across all lines of therapy and Waldenstrom’s macroglobulinemia patient subgroups that were studied,” Graef said in a statement at the time. “These promising findings build on our commitment to exploring the full potential of Imbruvica alone and in combination with other treatments. If approved, this chemotherapy-free combination will provide another treatment opportunity for patients living with this rare disease, which continues to have very limited treatment options.”