Incyte has become the latest company to pull an FDA filing following Gilead and Secura Bio, which both voluntarily withdrew therapies that had been granted accelerated approval but hadn’t completed confirmatory studies for full approval.
Incyte has withdrawn a submission for approval for parsaclisib, a phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor for the treatment of relapsed or refractor follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL). The move was a business decision and not motivated by any changes to the efficacy or safety of parsaclisib, according to Incyte.
The FDA accepted a New Drug Application for parsaclisib In November 2021 based on submission data from several phase 2 studies that showed parsaclisib was generally well tolerated with a manageable safety profile. The drug was granted Priority Review for the treatment of adults with relapsed or refractory MZL who received at least 1 prior anti–CD20-based regimen and for adults with MCL who received at least 1 prior therapy.
According to the company, the decision was made after discussions with the FDA “regarding confirmatory studies to support an accelerated approval, which Incyte determined cannot be completed within a time period that would support the investment.”
The company’s decision only impacts the FL, MZL, and MCL indications in the United States and does not affect other ongoing trials.
The move comes shortly after Gilead Sciences voluntarily withdrew the indications of its PI3Kδ inhibitor, idelalisib (Zydelig), in patients with relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma (SLL).
Idelalisib was granted accelerated approval in combination with rituximab (Rituxan) in July 2014 based on results of a phase 2 trial that found idelalisib had an objective response rate (ORR) of 54% in patients with FL and 58% in patients with SLL. However, the continued approval for these indications was contingent on providing evidence to support confirmation of the clinical benefit in FL and SLL.
According to Gilead, “enrollment into the confirmatory study has been an ongoing challenge,” which led to the decision to voluntarily withdraw these indications.
Idelalisib will remain on the market in the US for chronic lymphocytic leukemia (CLL).
Kite, a Gilead company, currently has the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) approved to treat large B-cell lymphoma or FL after 2 or more lines of systemic therapy. In October 2021, Kite submitted a supplemental Biologics License Application to the FDA to expand the indication of the CAR T-cell therapy to include second-line treatment of patients with relapsed or refractory large B-cell lymphoma based on the results of the phase 3 ZUMA-7 study.
At the 63rd Annual American Society of Hematology Meeting and Exposition, the lead author of ZUMA-7 said axi-cel “should be a new standard for patients with second-line relapsed/refractory large B-cell lymphoma.”
The trial has shown that axi-cel improved event-free survival (EFS) more than 60% over standard of care (SOC). The median EFS was 8.3 months for axi-cel vs 2.0 months for SOC, and the ORR was 83% for axi-cel vs 50% for SOC.
Even before Gilead, Secura Bio had withdrawn the indication of duvelisib (Copiktra) for use in patients with relapsed or refractory FL after 2 or more systemic therapies. Similar to idelalisib, duvelisib was granted accelerated approval and Secura needed to conduct an additional confirmatory trial to receive full approval.
In December 2021, Secura announced that after a strategic assessment of duvelisib and the FL space, as well as subsequent consultation with the FDA, “a more prudent application of future effort and resource is in new application for T-cell lymphoma where initial data appear encouraging.”
Duvelisib will remain on the market in the United States for CLL and SLL.