Johnson & Johnson and AbbVie’s Imbruvica has enjoyed a nice run in previously untreated chronic lymphocytic leukemia over the last few years. But major competition is here in the form of AstraZeneca’s Calquence.
Thursday, the FDA green-lighted Calquence in newly diagnosed CLL or small lymphocytic lymphoma. The agency based the decision on a pair of phase 3 trials showing that Calquence could top standard therapies at staving off cancer progression.
The approval was the second under Project Orbis, which allows for concurrent submission to the FDA and its international partners. The FDA also examined AZ's application under its real-time oncology review program, which allows the agency to begin sifting through data before a company submits its full application.
The go-ahead is a big one for AZ, which is looking to give rival BTK inhibitor Imbruvica a run for its money. Analysts have foreshadowed a CLL showdown between the two drugs ever since Calquence first hit the scene with a nod in mantle cell lymphoma, which represents a smaller market opportunity than CLL does.
But some industry watchers don’t expect the British drugmaker to have an easy time stealing share—at least, not without head-to-head trial data.
Knocking Imbruvica aside in CLL is “not going to be easy” for Calquence, UBS analyst Michael Leuchten wrote in a note to clients in May after reviewing phase 2 study data presented at ASCO. “Calquence has a place as a second-line treatment but not much more than that,” he added.
Imbruvica, of course, has plenty of clinical data to back it up in the front-line setting. As of last year’s American Society of Hematology annual meeting, it had come up big in four phase 3 CLL studies that were “really made complementary,” according to Danelle James, M.D., head of clinical science at AbbVie’s Pharmacyclics.
“They have almost mutually exclusive populations, but they cover the entire spectrum of CLL,” James said at the time, adding that in “the front-line setting, it’s almost like no patient left behind.”
Imbruvica has also had years on the market without company from Calquence after snagging its first-line go-ahead in March of 2016. Through the first nine months of this year, it reeled in $2.5 billion across all its indications, compared with just $108 million for Calquence.
But AZ execs are confident they’ll see that number balloon on the back of the new OK. CLL is the most common form of leukemia, with an estimated 191,000 new cases globally and 20,720 new cases in the U.S. each year, AstraZeneca has said.
Meanwhile, both Calquence and Imbruvica could be under threat from BeiGene’s freshly approved BTK inhibitor Brukinsa. While that drug has nabbed its first FDA nod in mantle cell lymphoma, it’s also eyeing the CLL/SLL market. The Chinese biotech is already testing Brukinsa against a combo of Teva’s Treanda and Roche’s Rituxan in the phase 3 Sequoia trial in previously untreated CLL/SLL, with a primary completion date set for next September.
Like AstraZeneca, Beigene is also taking on Imbruvica in a head-to-head study. It last year started the phase 3 Alpine trial that’s pitting Brukinsa against Imbruvica in relapsed/refractory CLL. Before that, industry watchers will be looking for data from the phase 3 Aspen trial that compares the two drugs in Waldenstrom macroglobulinemia for signs of whether Brukinsa can compete in CLL. It’s expected to read out by year’s end.
Editor's note: This article previously incorrectly stated that regulators in Canada and Australia had also approved Calquence.