Gilead Voluntarily Withdraws Two Accelerated Approvals for Zydelig Amid Evolving Lymphoma Treatment Landscape

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As early as 2014, Gilead's Zydelig became the first PI3K inhibitor drug approved by the FDA for B-cell blood cancers. Fast forward to today, with the emergence of more treatment options, Gilead has had to voluntarily withdraw two indications that Zydelig received under the accelerated approval pathway due to treatment data concerns.

Gilead Withdraws Zydelig’s Use in Relapsed Follicular Lymphoma (FL) and Relapsed Small Lymphocytic Lymphoma (SLL) Due to Inability to Complete FDA-Required Confirmatory Trials. The company stated that this move will not affect Zydelig's use for relapsed chronic lymphocytic leukemia, an indication approved under the FDA’s regular approval process.

The drug was withdrawn this time because the FDA has recently paid more attention to accelerated approval drugs that failed to meet post-approval trial requirements. As Gilead pointed out, the treatment landscape for these two subtypes of indolent non-Hodgkin lymphoma has changed. Based on clinical phase II data showing tumor response to the drug, Gilead received accelerated approval for FL and SLL. However, subsequently launched drugs have already published mature clinical efficacy data.

Bayer announced in April 2021 that its PI3K inhibitor Aliqopa, when used in combination with Roche's Rituxan, reduced the risk of disease progression or death by 48% in patients with indolent non-Hodgkin lymphoma who had received one prior treatment, compared to Rituxan alone. Bayer hopes to use the new Phase III data to convert Aliqopa’s accelerated approval for third-line treatment of follicular lymphoma into a full approval.

Zydelig's own combination therapy trial with Rituxan was prematurely halted in 2016 after reporting multiple deaths in its clinical program. Due to safety concerns, Zydelig's sales never met expectations, with global sales reaching only $50 million in the first nine months of 2021.

Other PI3K options that may be safer than Zydelig, such as TG Therapeutics' Ukoniq, have also received FDA approval for later-line treatment and are undergoing clinical trials to move earlier in the treatment sequence. Additionally, AbbVie and Johnson & Johnson's BTK inhibitor Imbruvica has been able to treat newly diagnosed CLL and SLL patients, thanks to the FDA's 2016 approval based on disease progression data.

Gilead Admits Recruiting Patients for Zydelig’s Clinical Validation Study is a Challenge Amid Changing Treatment Landscape

FDA Recently Revisits Drugs Approved via Accelerated Approval in Oncology Without Confirmatory Trials. This action has led to the withdrawal of several cancer drug indications, most notably several PD-1/L1 inhibitors, including Merck's Keytruda, Bristol-Myers Squibb's Opdivo, AstraZeneca's Imfinzi, and Roche's Tecentriq.

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