EHA: A shorter leukemia therapy? AbbVie, J&J tee up FDA filing for Imbruvica, Venclexta fixed-duration combo

Imbruvica
AbbVie and Johnson & Johnson eye FDA approval for a fixed-duration combination of Imbruvica and Venclexta for previously untreated chronic lymphocytic leukemia. (AbbVie, Johnson & Johnson)

AbbVie and Johnson & Johnson already boast three FDA-approved regimens for Imbruvica in newly diagnosed chronic lymphocytic leukemia (CLL). Now, the pair aims to add another to the drug’s label, one that could shorten the time patients need to stay on treatment.

A combination of Imbruvica and AbbVie and Roche’s Venclexta slashed the risk of cancer progression or death by 78.4% compared with a cocktail of Roche’s Gazyva and the chemotherapy chlorambucil in previously untreated CLL. The data, from the phase 3 GLOW trial, were shared at the European Hematology Association (EHA) annual meeting.

Compared with existing Imbruvica therapies, where patients take the BTK inhibitor daily—potentially for years—until their disease progresses, the new Venclexta combo caps treatment at about 14 months. That could offer a new option for “probably younger patients with CLL that prefer more flexible, treatment-free intervals,” said Craig Tendler, M.D., vice president of oncology clinical development and global medical affairs at J&J’s Janssen unit, during an interview.

Same as Imbruvica’s original monotherapy use, the Venclexta combo offers a convenient oral treatment, while the drug’s two other approved cocktails—with Gazyva or Roche’s Rituxan—involve infusions.

RELATED: ASCO: AbbVie, J&J pad Imbruvica's CLL case with Venclexta fixed-duration combo data

One key question for the fixed-duration combo is whether it can sustain remission after treatment has stopped. In the preliminary analysis of the GLOW trial, at three months after treatment ended, 51.9% of the Imbruvica-Venclexta patients had undetectable measurable residual disease (uMRD)—a stringent marker reflecting no signs of cancer—in bone marrow, versus 17.1% for the control group. The rates for peripheral blood were 54.7% and 39% for the two groups, respectively.

From the three-month point onward, 84.5% of uMRD patients maintained that deep remission in the blood to the 12-month assessment. These data show the new combo can deliver “very durable remissions” for the vast majority of patients, Tendler said.

To persuade doctors to stop treatment for a traditionally continuous therapy, AbbVie and J&J likely also need to show that doing so won’t hurt patients’ chance at successful retreatment if their cancer does rebound early.

RELATED: ASCO: AstraZeneca details Calquence's heart safety edge over Imbruvica as both brace for BeiGene's rival Brukinsa

The GLOW trial doesn’t yet have the answer to that question, but Tendler pointed to encouraging early evidence from the regimen’s phase 2 trial, dubbed CAPTIVATE. Among eight patients who progressed after stopping the fixed-duration combo, six responded to subsequent Imbruvica monotherapy, while the other two didn’t have a response report, according to data presented at the recent American Society of Clinical Oncology annual meeting.

While they are early data, “it’s also very reassuring that those patients who have progressed can be rather easily reinduced into remission,” Tendler said. J&J and AbbVie are now taking the same approach for the GLOW study, he added.

RELATED: EHA: Watch out, Imbruvica. BeiGene's touting Brukinsa efficacy, safety wins in a key leukemia battleground

As the first-to-market BTK inhibitor, Imbruvica has been treating front-line CLL patients since its monotherapy go-ahead in early 2016. But it’s now facing competition from AstraZeneca’s Calquence, which just detailed a head-to-head safety advantage over Imbruvica in previously treated CLL.

What’s more, also at the EHA meeting, BeiGene’s Brukinsa showed it could outperform Imbruvica at triggering tumor responses while causing fewer cases of atrial fibrillation, a potentially dangerous heart side effect, in its own head-to-head phase 3 study in previously treated CLL.

The third-to-market BTK inhibitor is also looking to report top-line results from a front-line trial later this year. Imbruvica could feel more pressure if that study also turns out successful.