Parsaclisib New Drug Application Withdrawn for Relapsed/Refractory MCL, MZL, and Follicular Lymphoma

The new drug application for parsaclisib, an oral PI3Kδ inhibitor, has been withdrawn for patients with relapsed/refractory mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and follicular lymphoma, according to an update on the drug’s clinical development.¹

Incyte made the decision to withdraw the application following discourse with the FDA about the need for confirmatory studies in support of an accelerated approval, as the research would not be completed within the required time period. Notably, the decision is business-based, with the company noting that the safety and efficacy of parsaclisib have not changed. The decision will only apply to MCL, MZL, and follicular lymphoma indications within the United States and will not apply to other clinical trials domestically or internationally.

Parsaclisib was most recently assessed as part of the phase 2 CITADEL-205 trial (NCT03235544) in a population of patients with relapsed/refractory MCL who had not previously undergone treatment with a BTK inhibitor.² Patients who enrolled on the study were set to received either the weekly dosing regimen of 20 mg of parsaclisib once daily for 8 weeks followed by 20 mg weekly, or the daily dosing regimen, in which the subsequent dose was 2.5 mg.

In the overall population of 108 patients, investigators reported an overall response rate (ORR) of 68.5% (95% CI, 58.9%-77.1%). For the daily dosing group, the ORR was 70.1% (95% CI, 58.6%-80.0%). The complete response rates were 17.6% (95% CI, 10.9%-26.1%) and 15.6% (95% CI, 8.3%-25.6%) in the overall and daily dosing populations, respectively.

Among those who responded to treatment, 89.2% of patients responded by the first disease assessment. Additionally, the median duration of response was 13.7 months in the overall population and 12.1 months in the daily dosing cohort. Investigators also reported a median progression-free survival of 11.99 months (95% CI, 8.3-16.9) and 13.6 months (95% CI, 10.0-16.9) in the overall population and daily dosing group, respectively.

Treatment-emergent adverse effects (TEAEs) were reported in 90.7% of patients, with grade 3 or higher TEAEs occurring in 62.0% of patients. Common any grade TEAEs included diarrhea (34.3%), pyrexia (17.6%), and constipation (13.0%), with frequent grade 3 or higher TEAEs being diarrhea (13.9%) and neutropenia (8.3%). Additionally, the most common TEAEs leading to discontinuation were diarrhea (11.1%), colitis (4.6%), and hypokalemia (2.8%).

References

1. Incyte provides update on parsaclisib and MCLA-145. News release. Incyte. January 25, 2022. Accessed January 26, 2022. https://bit.ly/3r3EqhQ
2. Mehta A, Trněný M, Walewski J, et al. Efficacy and safety of parsaclisib in patients with relapsed or refractory mantle cell lymphoma not previously treated with a BTK inhibitor: primary analysis from a phase 2 study (CITADEL-205). Blood. 2021;138(suppl 1):382. doi:10.1182/blood-2021-147867