Gilead pulls 2 cancer accelerated approvals as changing lymphoma landscape disrupts confirmatory trial

Back in 2014, Gilead Sciences’ Zydelig became the first PI3K inhibitor cleared by the FDA for certain B-cell blood cancers. Fast forward to today, and the company has found itself withdrawing two indications gained under the accelerated approval pathway as more treatments have become available.

Gilead is pulling Zydelig’s uses in relapsed follicular lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL), citing failure to complete an FDA-mandated confirmatory trial. The move doesn’t affect Zydelig’s relapsed chronic lymphocytic leukemia use, which was earned with a full FDA go-ahead, the company said.

The retraction comes as the FDA is paying more careful attention to accelerated approvals that have failed to meet postapproval trial requirements. And as Gilead noted, the treatment landscape for the two indolent non-Hodgkin lymphoma subtypes has changed.

Gilead won accelerated approvals for FL and SLL based on phase 2 data showing tumor responses. But drugs that came after it have posted mature clinical efficacy data.

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Bayer’s rival PI3K inhibitor Aliqopa, used on top of Roche’s Rituxan, cut the risk of disease progression or death by 48% over Rituxan alone in patients with indolent non-Hodgkin’s lymphoma who had already received one prior therapy, Bayer unveiled in April 2021. Bayer hopes to use the new phase 3 data to turn Aliqopa’s accelerated approval for third-line treatment of follicular lymphoma into a full approval.

Zydelig’s own Rituxan combo trials were stopped early after reports of multiple deaths in its clinical programs in 2016. Because of that safety concern, Zydelig’s sales never picked up, with merely $50 million in global sales in the first nine months of 2021.

Other potentially safer PI3K options than Zydelig, such as TG Therapeutics’ Ukoniq, have also won FDA approvals in the late-line setting and are undergoing clinical trials to move earlier in the treatment sequence.

Plus, AbbVie and Johnson & Johnson’s BTK inhibitor, Imbruvica, has been able to treat newly diagnosed CLL and SLL patients thanks to an FDA nod in 2016 based on disease progression data.

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Pointing to the evolved treatment landscape, Gilead admitted that enrollment into Zydelig’s confirmatory study has been a challenge.

Gilead’s decision also comes shortly after Secura Bio made a similar move for Verastem Oncology-inherited PI3K med Copiktra. In December, Secura voluntarily pulled Copiktra’s third-line FL indication off the U.S. market. The company at the time said it had determined that “the current treatment landscape for FL patients in the U.S. and the logistics, cost and timing of the postmarketing requirements for Copiktra in FL was no longer merited.”

The FDA recently launched an industrywide campaign targeting accelerated approvals in oncology with unresolved confirmatory trials. The initiative has triggered the withdrawal of several cancer drug indications, most notably for PD-1/L1 inhibitors including Merck’s Keytruda, Bristol Myers Squibb’s Opdivo, AstraZeneca’s Imfinzi and Roche’s Tecentriq.