FDA’s ODAC Votes Against Duvelisib for Previously Treated CLL/SLL

An 8-to-4 vote was cast by the FDA’s Oncologic Drugs Advisory Committee against the use of duvelisib in previously treated chronic lymphocytic leukemia and small lymphocytic leukemia.

Duvelisib (Copiktra) received a vote of 8 to 4 from the FDA’s Oncologic Drugs Advisory Committee (ODAC) against the agent’s use in chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) previously treated with at least 2 therapies, with experts citing an unfavorable risk/benefit profile.1

“This agent may work for some patients and may delay progression, but ultimately [these] data do not support that this agent does prolong life, and on the contrary, appears to lead to extra toxicity for some,” ODAC chairperson Jorge Garcia, MD, director of the genitourinary medical oncology clinical and research programs at University Hospitals Seidman Cancer Center in Cleveland, Ohio, said during the meeting.

The PI3K inhibitor was approved in capsule form by the FDA in September 2018 for relapsed/refractory CLL/SLL after treatment with at least 2 therapies.2 The designation was supported by findings from the phase 3 DUO study (NCT02004522), the initial results of which highlighted a significant improvement in progression-free survival (PFS) and overall response rate (ORR) following treatment with duvelisib at a dose of 25 mg twice daily vs ofatumumab. In particular, the median PFS was 13.3 months in the experimental arm vs 9.9 months in the control arm (P <.0002). The ORR was 74% vs 45% in each respective arm (P <.0001).

However, in July 2022, the FDA cited concerns around a potential increased risk of death and serious adverse effects (AEs) associated with duvelisib in patients with CLL/SLL.3 Serious AEs associated with the agent included infections, diarrhea, intestinal and lung inflammation, skin reactions, and increased liver enzymes.

An application for duvelisib also was also voluntarily withdrawn as a treatment for relapsed/refractory follicular lymphoma in December 2021, as the logistics, costs, and timing needed to achieve post-marketing approval requirements could no longer be justified.4 Of note, the withdrawal did not pertain to the agent’s safety or efficacy.

“In the end, I do have concerns about this class of medications. If we’re not clearly improving overall survival in our patients, but we’re increasing toxicity and treatment-associated death, I’m not sure that we’re truly helping patients,” Christopher Lieu, MD, associate director for clinical research and co-director of gastrointestinal medical oncology at the University of Colorado Cancer Center in Aurora, Colorado, stated during the meeting.


  1. September 22-23, 2022 Meeting of the Oncologic Drugs Advisory Committee (ODAC) - Day 2. Streamed live September 23, 2022. Accessed September 26, 2022. https://bit.ly/3fj2biw
  2. Verastem Oncology receives FDA approval of COPIKTRA™ (duvelisib) capsules. News release. September 24, 2018. Accessed September 28, 2022. https://bit.ly/3LHplLH
  3. FDA warns about possible increased risk of death and serious side effects with cancer drug Copiktra (duvelisib). News release. FDA. June 30, 2022. Accessed September 26, 2022. https://bit.ly/3PAlZLl
  4. Secura Bio announces Copiktra® (duvelisib) strategic focus on T-cell lymphoma and voluntary U.S. withdrawal of the relapsed or refractory follicular lymphoma indication. News release. Secura Bio. December 3, 2021. Accessed September 26, 2022. https://prn.to/3arGI4P