FDA Asks for More Data on Zandelisib

After a meeting with the U.S. Food and Drug Administration (FDA) the manufacturers of zandelisib – MEI Pharma and Kyowa Kirin – will not file for marketing approval of the drug based on results of the single-arm phase 2 TIDAL trial.

The FDA told the manufacturers that a randomized clinical trial is now needed to “adequately assess drug efficacy and safety” of phosphatidylinositol-3-kinase (PI3K) inhibitors.

Zandelisib, a selective PI3Kδ inhibitor, is developed as an oral treatment for patients with B-cell malignancies. In late 2021, data from the phase 2 TIDAL study showed that zandelisib had a 70.3% objective response rate as a monotherapy in patients with follicular lymphoma who had received at least two prior therapies. About one-third (35.2%) of patients had a complete response.

In March 2020, the FDA granted zandelisib Fast Track designation for the treatment of adult patients with relapsed/refractory follicular lymphoma who had at least two prior therapies. In November 2021, the FDA granted the drug Orphan Drug designation for this patient population.

The FDA has discouraged the filing for market authorization of zandelisib under the accelerated approval pathway based on data from the phase 2 TIDAL study. Instead, the manufacturers were encouraged to continue efforts of the ongoing phase 3 COASTAL study, which compares zandelisib plus rituximab to standard of care chemotherapy plus rituximab. Included patients had relapsed or refractory follicular lymphoma or mantle zone lymphoma and have received one or more prior lines including an anti-CD20 antibody in combination with chemotherapy or lenalidomide.