Roche’s CD20xCD3 Bispecific Antibody Mosunetuzumab Receives FDA Breakthrough Therapy Designation for Relapsed/Refractory Follicular Lymphoma

July 14, 2020 News /BioValleyBIOON/ -- Roche recently announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to mosunetuzumab, a T-cell-engaging CD20xCD3 bispecific antibody, for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have previously received at least two systemic therapies.

Breakthrough Therapy Designation (BTD) is a new drug review pathway established by the FDA in 2012, aimed at accelerating the development and review of new drugs intended to treat serious or life-threatening diseases, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies. Drugs granted BTD can receive, during development, includingFDACloser guidance, including from senior officials, to ensure that new treatment options are made available to patients in the shortest possible time.

FDABreakthrough Therapy Designation (BTD) was granted to mosunetuzumab based on encouraging efficacy results observed in the Phase I/Ib GO29781 study (NCT02500407). This multicenter, open-label, dose-escalation Phase I/Ib study evaluated the safety and pharmacokinetics of mosunetuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). The enrolled patient population included those who had relapsed after or were refractory to CAR-T cell therapy, a group with limited treatment options. The study aimed to assess the best overall objective response rate (ORR, evaluated using the revised International Workshop Criteria), maximum tolerated dose, and tolerability.

Results presented at the 2019 American Society of Hematology (ASH) annual meeting late last year demonstrated encouraging efficacy for mosunetuzumab: (1) The overall response rate (ORR) was 62.7% (n=42/67) in patients with indolent non-Hodgkin lymphoma (NHL) and 37.1% (n=46/124) in patients with aggressive NHL. (2) The complete response (CR) rate was 43.3% (n=29/67) in patients with indolent NHL and 19.4% (n=24/124) in patients with aggressive NHL. (3) CR responses proved durable, with 82.8% (n=24/29) of patients with indolent NHL remaining in remission 26 months after initial treatment, and 70.8% (n=17/24) of patients with aggressive NHL remaining in remission 16 months after initial treatment. (4) In patients who had previously received CAR-T cell therapy, the ORR was 38.9% (n=7/18) and the CR rate was 22.2% (n=4/18). (5)Adverse ReactionsIn terms of adverse events, 28.9% of patients experienced cytokine release syndrome (CRS), with 20.0% being Grade 1 and 1.1% being Grade 3; Grade 3 neurological adverse events occurred in 3.7% of patients.

Levi Garraway, M.D., Chief Medical Officer and Head of Global Product Development at Roche, stated, “We are pleasedFDA“The granting of Breakthrough Therapy Designation to mosunetuzumab indicates the agency’s recognition of the drug’s early efficacy data as well as the unmet medical needs that remain in the field of follicular lymphoma (FL). Indeed, we are excited about the potential of CD20xCD3 bispecific antibodies (mosunetuzumab and glofitamab) in the clinical development for refractory lymphoma, and we remain committed to developing innovative therapies to improve patient outcomes.”

Mosunetuzumab and glofitamab (formerly known as CD20-TCB) are both CD20xCD3 T-cell-engaging bispecific antibodies that target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects the patient’s existing T cells to eliminate target B cells by releasing cytotoxic proteins into the B cells.

The two antibodies differ structurally. Mosunetuzumab resembles a natural human antibody but contains two Fab regions, one targeting CD20 and the other targeting CD3. Glofitamab features a novel “2:1” structural format, with two Fab regions targeting CD20 and one Fab region binding to CD3. These two antibodies are part of Roche’s exploration of several bispecific antibody formats to identify the approach that offers maximal potential clinical benefit for patients. Currently, Roche is developing mosunetuzumab and glofitamab as monotherapies and in combination with other agents for the treatment of CD20-positive B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma and follicular lymphoma.

It is worth noting that in April this year, Zai Lab and Regeneron entered into a strategic collaboration for the development and commercialization of REGN1979, a CD20xCD3 bispecific antibody, in mainland China, Hong Kong, Taiwan, and Macau. Under the agreement, Zai Lab will pay Regeneron an upfront payment of $30 million, followed by up to $160 million in regulatory and sales milestone payments. Zai Lab will share part of the global development costs for REGN1979 and obtain rights in mainland China, Hong Kong, Taiwan, and Macau forTumorDevelopment and exclusive commercialization rights in the field. In early July, five clinical trial applications for REGN1979 were accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA).

REGN1979 has been approved in the United StatesFDAOrphan Drug Designation (ODD) granted for the treatment of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). REGN1979 is currently being evaluated in a Phase I clinical trial and a Phase II clinical trial, which may serve as a registrational study, in patients with advanced FL, DLBCL, and other lymphomas.

Positive Data from the Phase I Clinical Study of REGN1979 Presented at ASH 2019MeetingPublished data showed that REGN1979 monotherapy for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) demonstrated increased efficacy at higher doses: 5 out of 8 patients treated with 80/160/320 mg achieved complete response (CR), and 2 out of 3 patients who had failed CAR-T therapy achieved CR.

Furthermore, monotherapy with REGN1979 for relapsed or refractory follicular lymphoma (R/R FL) also demonstrated a dose-dependent increase in efficacy: 13 out of 14 patients receiving ≥5 mg achieved disease response, with an overall response rate (ORR) of 93% (n=13/14) and a complete response rate (CR) of 71.4% (n=10/14). (Bioon.com)

Original Source:FDA grants Breakthrough Therapy Designation for Roche’s CD20xCD3 bispecific cancer immunotherapy mosunetuzumab recognising its potential in follicular lymphoma