The Food and Drug Administration (FDA) has accepted for review the New Drug Application for parsaclisib for the treatment of patients with relapsed or refractory follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL).
The FDA’s Priority Review has been granted to parsaclisib for the treatment of adults with relapsed or refractory MZL who have received at least 1 prior anti-CD20-based regimen and for the treatment of adults with MCL who have received at least 1 prior therapy.
Parsaclisib is an investigational oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ). The application is supported by data from several phase 2 studies evaluating parsaclisib for the treatment of adults with relapsed or refractory FL (CITADEL-203 [ClinicalTrials.gov Identifier: NCT03126019]), MZL (CITADEL-204 [ClinicalTrials.gov Identifier: NCT03144674]), and MCL (CITADEL-205 [ClinicalTrials.gov Identifier: NCT03235544]).
In all of these studies, patients received parsaclisib 20mg once daily for 8 weeks followed by either 20mg once weekly (weekly-dosing group) or 2.5mg once daily (daily-dosing group [DG]). Patients initially enrolled in the weekly dosing group were allowed to switch to daily dosing as it was subsequently selected as the preferred regimen. The primary endpoint was objective response rate (ORR). Key secondary endpoints including duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
Results from CITADEL-203 showed that among all 118 FL patients, the ORR was 73% (95% CI, 64-81), median DOR was 15.9 months (95% CI, 12-not evaluable [NE]), and median PFS was 15.8 months (95% CI, 13.2-19.3). Among the 95 patients in the DG group, the ORR was 75% (95% CI, 65-83), median DOR was 14.7 months (95% CI, 12-17.5), and median PFS was 15.8 months (95% CI, 13.8-19.1).
In CITADEL-204, among all 100 MZL patients, the ORR was 57% (95% CI, 46.7-66.9), median DOR was 12 months (95% CI, 9.3-NE), and median PFS was 19.4 months (95% CI, 13.7-NE). Among the 72 patients in the DG group, the ORR was 56.9% (95% CI, 44.7-68.6), median DOR was not reached (95% CI, 8.1-NE), and median PFS was also not reached (95% CI, 11-NE).
Findings from CITADEL-205 showed that among the 77 MCL patients in the DG group who were Bruton tyrosine kinase inhibitor treatment naive, the ORR was 71% (95% CI, 60-81), median DOR was 9 months (95% CI, 6.7-14.7), median PFS was 11.1 months (95% CI, 8.3-NE), and median OS was not yet reached. Among the 41 MCL patients in the DG group who were previously treated with ibrutinib, the ORR was 29% (95% CI, 16-46), median DOR was 3.7 months (95% CI, 1.9-NE), median PFS was 3.7 months (95% CI, 1.8-4.1), and median OS was 11.2 months (95% CI, 7.9-NE).
As for safety, parsaclisib was generally well tolerated in all studies with a manageable safety profile.
“Non-Hodgkin lymphomas are some of the most common cancers in the United States, and the FDA’s acceptance of this NDA represents an important milestone for Incyte and for NHL patients who have not responded to or who have progressed on initial therapies,” said Peter Langmuir, MD, Group Vice President, Oncology Targeted Therapies, Incyte. “We look forward to working with the FDA to bring this innovative therapy to patients who may benefit.”
A Prescription Drug User Fee Act (PDUFA) target date of April 30, 2022 has been set for the MZL and MCL indication reviews. For the FL indication, the PDUFA target date is August 30, 2022.
- Incyte announces acceptance of NDA for parsaclisib for three types of relapsed or refractory non-hodgkin lymphomas. News release. Incyte. November 1, 2021. Accessed November 2, 2021. https://investor.incyte.com/press-releases/press-releases/2021/Incyte-Announces-Acceptance-of-NDA-for-Parsaclisib-for-Three-Types-of-Relapsed-or-Refractory-Non-Hodgkin-Lymphomas/default.aspx.
- Incyte announces parsaclisib treatment results in high rate of rapid and durable responses in patients with relapsed or refractory B-cell non-hodgkin lymphomas. News release. Incyte. December 7, 2020. Accessed November 1, 2021. https://www.businesswire.com/news/home/20201207005129/en/Incyte-Announces-Parsaclisib-Treatment-Results-in-High-Rate-of-Rapid-and-Durable-Responses-in-Patients-with-Relapsed-or-Refractory-B-Cell-Non-Hodgkin-Lymphomas.