AbbVie, J&J blockbuster Imbruvica rakes in 11th FDA approval, as competitors work on eroding franchise
AbbVie and J&J’s market-leading Imbruvica, the original BTK inhibitor, continues to rake in approvals, while competition in the class of drugs heats up.
On Tuesday, the drug secured its 11th FDA approval. Imbruvica in combination with Roche’s rituximab has been sanctioned for use as the first line of defense in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Imbruvica inhibits Bruton’s tyrosine kinase (BTK), an enzyme that plays a crucial role in oncogenic signaling that is 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 BTK inhibitors, such as AstraZeneca’s Calquence, have been positioned as safer but equally efficacious alternatives.
In December, China-based BeiGene’s quest to overshadow market-leading Imbruvica with its own BTK inhibitor fell through after a head-to-head study pitting the two therapies favored the AbbVie/J&J drug in patients with a rare form of lymphoma.
However, the safety profile of BeiGene’s Brukinsa did give it an edge in the open-label study, causing less atrial fibrillation and bleeding that could be clinically and commercially meaningful, SVB Leerink analyst Geoffrey Porges noted at the time.
Still, Porges stuck by his sales forecast for Imbruvica — to grow from $4.7 billion in 2019 to $7.7 billion in 2022 to $8.9 billion in 2024 to $10 billion in 2026, before losing exclusivity and eroding rapidly in the 2028-2031 period.
“Our forecast assumes continued dominance of the CLL indication by AbbVie/JNJ’s Imbruvica, with only 30% share loss for Imbruvica in CLL by 2024 and 33% by 2026,” he said. “Should zanubrutinib confirm better safety (on atrial fibrillation and major hemorrhage) compared to Imbruvica in the CLL pivotal trials, then the share loss for Imbruvica could be greater than we currently forecast.”
The Imbruvica+rituximab approval for first-line CLL and SLL patients was based on data from the E1912 study, which tested the Imbruvica regime against standard-of-care treatment: the chemoimmunotherapy regimen of fludarabine, cyclophosphamide and rituximab (FCR).
Data from the trial involving 529 previously untreated CLL patients showed that after 3 years, the percentage of patients with progression-free survival was 89.4% in the Imbruvica group, versus with 72.9% in the chemoimmunotherapy arm — meeting the main goal of the study. Data on overall survival also favored the Imbruvica group at 98.8%, as compared with 91.5% in the chemoimmunotherapy group, over the same time period.
“The gold-standard first-line treatment option for many patients with chronic lymphocytic leukemia who were fit enough to tolerate an aggressive treatment course had been the intravenous chemoimmunotherapy of FCR — that is, until today,” said Brian Koffman, the CMO of the CLL Society, in a statement.