Orphan drug designation granted to zandelisib for follicular lymphoma

Follicular lymphoma (FL) is an indolent (or slowly progressing) B-cell lymphoma that represents 20‒30% of all non-Hodgkin lymphomas (NHL). It is most commonly diagnosed in patients >65 years of age. Although rare, FL can transform into a more aggressive type of lymphoma called diffuse large B-cell lymphoma (DLBCL).

Zandelisib is a selective inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ) and is in development as a once daily oral treatment for patients with B-cell malignancies. It is currently being evaluated in several phase II and III clinical trials:

• The phase II TIDAL study (NCT03768505) is evaluating zandelisib as a single agent in patients with relapsed or refractory (R/R) FL and R/R marginal zone lymphoma (MZL) who have failed at least two prior systemic therapies, including chemotherapy and an anti-CD20 antibody.
• The phase III COASTAL study (NCT04745832) is evaluating zandelisib plus rituximab in patients with R/R FL and R/R MZL who have received at least one prior line of therapy, which must have included an anti-CD20 antibody in combination with chemotherapy or lenalidomide.
• A pivotal phase II study (NCT04533581) in Japan evaluating patients with indolent B-cell non-Hodgkin lymphoma (iNHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM).

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to zandelisib for the treatment of patients with FL. This designation, which is granted by the FDA to drugs that are intended for the treatment of a rare disease or condition (one that affects fewer than 200,000 individuals), carries incentives for the company, including tax credits, fee exemptions, and a period of market exclusivity.