ASH: AstraZeneca's Calquence, BeiGene's Brukinsa turn heads with new data, putting Imbruvica on notice

Brukinsa
BeiGene's Brukinsa and AstraZeneca's Calquence are both coming after J&J and AbbVie's Imbruvica in CLL. (BeiGene)

Johnson & Johnson and AbbVie’s Imbruvica currently reigns supreme in the previously untreated chronic lymphocytic leukemia (CLL) market. But newer members of its class are threatening, and both put up data over the weekend in other cancer types that might catch the attention of CLL prescribers down the line.

Sunday at the American Society of Hematology virtual annual meeting, AstraZeneca touted long-term phase 2 Calquence results showing previously treated mantle cell lymphoma (MCL) went a median 22 months without seeing their cancer worsen. And at three years of follow-up, more than half of patients taking Calquence were still alive.

The way AZ sees it, “the fact that we’re seeing a number of patients with deep, durable responses over time is helpful for reinforcing the efficacy of the medicine”­—even outside of MCL, Dave Fredrickson, EVP and global head of AstraZeneca’s oncology business unit.

And the numbers are particularly noteworthy considering that MCL “is an aggressive and difficult-to-treat blood cancer. It’s diagnosed at an advanced stage, and patients become resistant to treatment,” he added.

RELATED: AstraZeneca's Calquence steps up to challenge Imbruvica with big CLL green light

Specifically, AstraZeneca is hoping the data reinforce the case for Calquence in CLL—a much larger market. The BTK inhibitor won a first-line nod in the disease last November, setting up an in-class showdown with Imbruvica.

Since then, AZ’s drug has gone on to capture 35% of new CLL patients, and Fredrickson predicts that number could rise to 50% by the launch’s 18-month mark. One reason? Calquence’s safety and tolerability profile. “The medicine itself is resulting in really good experiences for physicians and their patients,” he said.

But Calquence isn’t the only BTK inhibitor looking to give Imbruvica a run for its money in CLL. BeiGene’s Brukinsa, which scored its first FDA go-ahead last year with a green light in MCL, is on a collision course with both Imbruvica and Calquence in that arena.

Sunday at ASH, industry watchers got a look at the drug in marginal zone lymphoma (MZL), another B-cell malignancy, where Brukinsa showed it could provoke a response in 74% of patients and obliterate cancer completely in 24% of them after just 10.7 months of follow-up.

Imbruvica, in its own phase 2 MZL trial, spurred a benefit in 48% of patients and eliminated cancer in 5% of them after one year of follow-up.

“What it tells me really is that consistently, across every tumor type, we are seeing numerically better overall response rates, as well as higher complete response rates, than may have been historically seen with other BTK inhibitors,” said Jane Huang, M.D., BeiGene’s chief medical officer in hematology.

While “it can be challenging” to compare numbers across trials, in part because of differences in patient populations, “I think you can look at general trends,” she added.

RELATED: BeiGene's Brukinsa misses in Imbruvica head-to-head, but analysts still chalk up a win

BeiGene is also looking to Brukinsa’s safety profile for an advantage over its older rival—and in that department, it has head-to-head data it can point to.

Last December, the company unveiled phase 3 results in Waldenstrom macroglobulinemia showing that while the study missed its primary endpoint, just 2% of patients experienced atrial fibrillation, compared with 15% of those taking Imbruvica.

“In general, investigators feel that for the most part safety is extrapolatable to other diseases,” Huang noted.

BeiGene will no doubt be referencing that head-to-head safety win as it moves into first-line CLL, where it could have phase 3 data as soon as next year, Huang said.