Roche's Mosunetuzumab, the First-in-Class CD20×CD3 Bispecific Antibody, Granted Priority Review in China for Relapsed/Refractory Follicular Lymphoma

Nov 30, 2023 12:19 CST Updated 12:19

Roche

Oncology Drug Research, Development, and Manufacturing

On November 30, 2023, Roche's Mosunetuzumab (RO7030816, Mosunetuzumab)Proposed for Priority Review by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA), for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Figure 1: Mosunetuzumab Proposed for Priority Review by CDE

Mosunetuzumab is aCD3×CD20 T-Cell Bispecific AntibodyTargeting CD20 on the surface of B cells and CD3 on the surface of T cells, it activates and redirects T cells through dual targeting, and releases cytotoxic proteins to eliminate target B cells. Mosunetuzumab has a structure similar to natural human antibodies, with two "Fab" regions. However, it differs from naturally occurring antibodies because one "Fab" region targets CD20, while the other "Fab" region targets CD3.

Figure 2: Mechanism of Action of Mosunetuzumab

In June 2022, Mosunetuzumab received conditional marketing approval in the EU for the treatment of follicular lymphoma (FL) in patients who have previously received at least two systemic therapies. In December of the same year, it was approved by the FDA for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy.

It is reported that this drug is the world's first approved CD20×CD3 T cell-engaging bispecific antibody for follicular lymphoma, and it is also Roche's "first-in-class" bispecific antibody therapy.

In terms of research data,An updated Phase II pivotal study of Mosunetuzumab confirms the drug's durable efficacy in FL patients who have received ≥2 lines of therapy.。

In terms of patient baseline: 90 patients were enrolled. Among them, 54 patients (60%) achieved CR as the best efficacy during treatment; 49 patients (54%) achieved CR at EOT; 1 CR patient experienced disease progression (PD) at C8; 4 CR patients after EOT. Among the 49 CR patients at EOT, 82% were in disease stage III/IV, with a median number of treatment lines being 3 (range: 2-10). As of July 8, 2022, the median follow-up time for the study was 28.6 months.

In terms of efficacy: Among the 49 patients who achieved CR at EOT, the median duration of CR (DOCR; investigator-assessed) was not reached; the 24-month DOCR rate after the first CR was 65% (95% CI 39-90). The median PFS was not reached; the 24-month PFS rate was 77% (95% CI 63-91). Two years after the end of fixed-cycle treatment, 67% of the 49 patients had not experienced a PFS event.

Figure 3-6: Clinical Research Status of Mosunetuzumab

In terms of indication layout, Mosunetuzumab is being studied not only for the treatment of follicular lymphoma but also forClinical studies have been conducted in various other types of non-Hodgkin lymphoma., including monotherapy or combination therapy with other drugs (such as lenalidomide, rituximab, and gemcitabine, etc.).

Figure 7: Key Clinical Trials of Mosunetuzumab in Non-Hodgkin Lymphoma

In fact, bispecific antibodies are an important advantage technology platform for Roche and one of the areas the company has heavily invested in. Roche's bispecific antibody platform belongs to the traditional Fc-full-length bispecific antibody platform, mainly including the KiH platform, CrossMab platform, and ART-lgG platform. According to the Insight database, Roche has nearly 30 early-stage pipelines of bispecific antibodies targeting tumors, mainly including targets such as GPRC5D/CD3, PD-1/LAG3, PD-1/TIM-3, HER2/CD3, WT1/CD3, and CEA/CD3.

Figure 8-9: Roche's R&D Pipeline

References:

[1] Decoding Roche's R&D Pipeline: Strategies, Breakthroughs, and Insights. Insight Database. 2023-06-29.

[2] [2023 ASCO/EHA/ICML] Professors Rong Liang and Wenyu Li: A New Era in the Treatment of Indolent Lymphoma, Obinutuzumab and Mosunetuzumab Bispecific Antibody Help Patients Achieve Remission. Hematologic Oncology News. 2023-06-26.

[3] Leukemia·Lymphoma, 2023,32(3): 143-146.

[4] Roche's official website, MedSci Medical website, etc.

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