AbbVie, J&J pull 2 Imbruvica accelerated approvals in lymphoma, giving way to AZ and BeiGene

Amid a market clash with rival medicines, AbbVie and Johnson & Johnson’s Imbruvica is losing two of its approved uses.

Thursday, AbbVie and J&J said they plan to voluntarily withdraw Imbruvica in previously treated mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).

The partners decided to pull the accelerated approvals after results from two phase 3 confirmatory trials failed to convince the FDA, the companies said.

MCL and MZL are relatively small indications for Imbruvica compared with its chronic lymphocytic leukemia (CLL) use, which isn’t affected by the withdrawals. But pulling out of these indications still marks a blow to an already declining brand.

Under siege from BeiGene’s Brukinsa and AstraZeneca’s Calquence, Imbruvica chalked up $3.4 billion in U.S. sales for AbbVie in 2022, down 21% year over year. Plus, Brukinsa’s head-to-head win against Imbruvica in CLL, followed by a pair of recent FDA approvals, has put Imbruvica on the back foot.

Between the two Imbruvica withdrawals, the MCL one comes as more of a surprise. Imbruvica actually met the primary endpoint of the phase 3 SHINE study, showing it could reduce the risk of disease progression or death by 25% in newly diagnosed MCL.

The drug, however, failed to significantly prolong patients’ lives, according to data shared at the 2022 American Society of Clinical Oncology annual meeting. At that time, Craig Tendler, M.D., vice president of oncology clinical development and global medical affairs at J&J’s Janssen, played down the lack of an overall survival showing, partly because many patients in the control arm went on to receive a BTK inhibitor following disease progression.

Still, an overall survival no-show after a progression-free survival win—paired with an increased rate of side effects—apparently raised a red flag at the FDA. Previously, the agency had set off sweeping market withdrawals of several PI3K inhibitors, also for blood cancers, following a similar pattern of clinical findings.

During an advisory committee meeting scrutinizing the PI3K drug class last April, the FDA raised a point that safety is also a measure of efficacy, especially when a drug’s side effects appear to hurt patients’ long-term survival outcomes.

As for the MZL indication, AbbVie and J&J said the phase 3 SELENE study had failed as Imbruvica didn’t stave off cancer progression or death in patients with previously treated MZL or follicular lymphoma. Detailed data will be presented at a future medical meeting, the pair said.

“We fully support the FDA accelerated approval pathway, which patients rely on for timely access to promising treatments that may improve or extend their lives,” Tendler said in a statement Thursday, while adding that J&J remains confident in Imbruvica’s remaining indications.

Once Imbruvica officially bows out of those indications, BeiGene’s Brukinsa will be the only BTK inhibitor available in the U.S. for relapsed or refractory MZL, thanks to its accelerated approval in 2021. In MCL, both Brukinsa and AstraZeneca’s Calquence boast accelerated approvals for patients who have received one prior therapy, and Eli Lilly’s Jaypirca just won a go-ahead as a late-line option.

All those medicines have their own confirmatory trial commitments to meet. But randomized clinical trials for indolent blood cancers can take a long time to read out: Imbruvica’s SHINE was launched in 2013.

For Brukinsa, BeiGene and the FDA have established February 2027 as the deadline for submitting confirmatory evidence in the MCL use. BeiGene has until October 2028 for the MZL indication.

Calquence’s projected completion date for confirming the MCL label is November 2024, according to the FDA.