The post-marketing requirements for duvelisib are no longer necessary, according to the FDA, and the agent has been withdrawn from the United States market for the treatment of patients with relapsed or refractory follicular lymphoma.
Duvelisib (Copiktra), which is indicated for the treatment of patients with relapsed or refractory follicular lymphoma (FL) after at least 2 prior systemic therapies, has been voluntarily withdrawn from the market by its developer Secura Bio, Inc, according to a press release by the company.1
In 2018, duvelisib was granted accelerated approval by the FDA for the withdrawn indication. Continued approval was contingent upon an additional confirmatory trial. The initial approval was based on data from the phase 3 DUO clinical trial (NCT02004522) and the phase 2 DYNAMO clinical trial (NCT01882803).2
In DUO, investigators evaluated duvelisib versus ofatumumab (Arzerra) in patients with relapsed or refractory chronic lymphocytic leukemia, small lymphocytic leukemia, or follicular lymphoma. A total of 319 patients were randomized 1:1 to either receive either therapy. Duvelisib was administered at 25 mg twice daily until disease progression or unacceptable toxicity, and ofatumumab was dose at 300 mg on day 1 followed by 7 weekly doses and 45 months doses of 2000 mg.
The primary end point of the study was progression-free survival (PFS), and the secondary end points included overall response rate (ORR), the number of patients with hematologic improvement, overall survival (OS), lymph node response, duration of response (DOR), treatment-related adverse events (TRAEs), and the number of patients with samples available for duvelisib pharmacokinetics.
In the study subgroups that were previously treated with at least 2 prior lines of therapy (n = 196), patients had a median age of 69 years (40-90, 88% had an ECOG performance score of 0 or 1, and 59% were male. Deletion 17p was detected at baseline in 22% of patients, and 52% had 1 or more tumors that were 5 cm or larger. Fifty-four percent of patients received 3 or more prior lines of treatment.
Overall, in DUO, duvelisib demonstrated a reduction in the risk of disease progression or death by 60% compared with the control. The median PFS was 16.4 months with duvelisib compared with 9.1 months with ofatumumab (HR, 0.40). The ORR observed with duvelisib was 78% compared with 39% in the ofatumumab arm.
In the DYNAMO trial, 129 patients with refractory indolent non-Hodgkin lymphomas, including FL received duvelisib as monotherapy. The FL cohort includes 83 patients, and the group was 68% male with a median age of 64 years (range, 30-82). Thirty-seven percent of patients had bulky disease at baseline, and 93% had an ECOG performance score of 0 or 1.
Patients in DYNAMO were assessed for the primary end point of ORR, as well as the secondary end points of the number of patients with TRAEs, DOR, PFS, OS, OK plasm concentration of duvelisib in metabolites, and time to response.
The ORR observed with duvelisib in the FL subgroup was 42%, which included 1 complete response and 34 partial responses. At the time the data were reported, responses were ongoing at 6 months in 43% of patients, and responses were ongoing at 12 months in 17%.
In terms of safety, the box warning for duvelisib notes that fatal and/or serious infections can occur in 31% of patients treated. In addition, 18% of those who receive duvelisib can experience fatal and/or serious diarrhea, 5% can have fatal and/or serious cutaneous reactions, and 5% can develop fatal and/or serious pneumonitis.
Given advances that have changed the treatment landscape of FL since the accelerated approval, the FDA no longer sees merit in the company meeting the post-marketing requirement. Instead, Secura Bio, Inc will focus its efforts on applications for T-cell lymphoma. No other indications for duvelisib will be impacted by the company’s decision.
In the coming weeks, Secura Bio plans to work with the FDA to revise the label for duvelisib and quickly notification healthcare providers about the change.
1. Bio announces Copiktra® (duvelisib) strategic focus on t-cell lymphoma and voluntary U.S. withdrawal of the relapsed or refractory follicular lymphoma indication. New release. December 6, 2021. Accessed December 6, 2021.
2. Verastem oncology receives FDA approval of COPIKTRA™ (duvelisib) capsules. News release. September 24, 2018. Accessed December 6, 2021.