FDA Grants Priority Review to Genentech’s for People Follicular Lymphoma Therapy

The U.S. Food and Drug Administration has granted Priority Review for Genentech’s mosunetuzumab, a potential first-in-class CD20xCD3 T-cell engaging bispecific antibody, for the treatment of adults with relapsed or refractory follicular lymphoma who have received at least two prior systemic therapies.

Photo: Levi Garraway, chief medical officer and head of Global Product Development

Follicular lymphoma is the most common slow growing form of non-Hodgkin’s lymphoma (NHL), a type of blood cancer, that often returns after initial therapy. It typically responds well to treatment but is often characterized by periods of remission and relapse. The disease typically becomes harder to treat each time a patient relapses, and early progression can be associated with poor long-term prognosis. In the United States, it is estimated that approximately 13,000 new cases of follicular lymphoma will be diagnosed in 2022.

Mosunetuzumab is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development program for mosunetuzumab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin’s lymphomas, including follicular lymphoma, diffuse large B-cell lymphoma and other blood cancers.

The FDA is expected to make a decision on approval of Mosunetuzumab by December 29, 2022.

Priority Review designation is granted to medicines that the FDA considers to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention, or diagnosis of a serious disease. The FDA granted Breakthrough Therapy designation to mosunetuzumab for the treatment of adults with relapsed or refractory follicular lymphoma who have received at least two prior systemic therapies in June 2020 and Orphan Drug Designation in December 2018.

The designation is designed to accelerate the development and review of medicines intended to treat serious or life-threatening conditions with preliminary evidence that indicates they may demonstrate substantial improvement over existing therapies. The European Commission granted conditional marketing authorization for mosunetuzumab for the treatment of people with relapsed or refractory follicular lymphoma who have received at least two prior systemic therapies in June 2022.

“New therapeutic options are needed for follicular lymphoma, which often relapses after initial therapy and becomes increasingly difficult to treat each time it returns. Clinical trial results have demonstrated durable responses with mosunetuzumab in advanced follicular lymphoma, representing a step toward shifting the treatment paradigm,” said Levi Garraway, chief medical officer and head of Global Product Development. “Since mosunetuzumab does not require the collection or genetic modification of patient cells, it could become an effective, fixed-duration outpatient option without the barriers of travelling to a major academic center.”

Genentech’s application for approval to market mosunetuzumab is based on positive results from the pivotal phase 1/2 study that showed high complete response (CR) rates, with the majority of responders (57 percent) maintaining responses for at least 18 months, and manageable tolerability in people with heavily pretreated FL.

After a median follow-up of 18.3 months, the CR rate was 60 percent, and the objective response rate was 80 percent. The median duration of response among those who responded was 22.8 months (95 percent).

The most common adverse event (AE) was cytokine release syndrome (39 percent), which was generally low grade (grade 1: 25.6 percent; grade 2: 14 percent; grade 3: 2.3 percent; grade 4: 0.5 percent), and all events resolved. Other common AEs (>20 percent) included fatigue, headache, neutropenia, fever, and hypophosphatemia. Treatment was administered without mandatory hospitalization. Results were presented for the first time in December 2021 at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition.

Author: Rare Daily Staff