Mosunetuzumab Approved Bispecific

Antibody Information

Entry ID	40
INN	Mosunetuzumab
Status	Approved
Drug code(s)	BTCT4465A, RG7828, RO7030816
Brand name	Lunsumio
mAb sequence source	mAb humanized
General Molecular Category	Bispecific
Format, general category	Full length Ab
Format details	None
Isotype (Fc)	IgG1
Light chain isotype	kappa
Linker	None
Ave. DAR	None
Conjugated/fused moiety	None
Discovery method/technology	None

Therapeutic information

Target(s)	CD20, CD3
Indications of clinical studies	Systemic Lupus Erythematosus, Chronic Lymphocytic Leukemia, Follicular Lymphoma, Diffuse Large B-cell Lymphoma, Non-Hodgkin's Lymphoma, NHL and Chronic Lymphocytic Leukemia (first Phase 1)
Primary therapeutic area	Cancer

Development stage information

Phase lengths*

*The graph represents early-stage clinical development phase lengths. For molecules approved or under evaluation for marketing authorization in the US is provided a complete overview of all clinical development phase lengths. Phase lengths are calculated from the start of the first in human (FIH) study (Start of clinical phase). “Start of Phase 2” bar represents Phase 1 length (Start of clinical phase to start of Phase 2); “Start of Phase 3” bar represents Phase 1+2 length (Start of clinical phase to start of Phase 3); “Date BLA/NDA submitted” bar represents Phase 1+2+3 length (Start of clinical phase to Date BLA/NDA submitted); and “Date of first US approval” bar represents Phase 1 to first US approval length (Start of clinical phase to Date of first US approval).

Most advanced stage of development (global)	Approved EU, US
Status	Active
Start of clinical phase (IND filing or first Phase 1)	September 01, 2015
Start of Phase 2
Start of Phase 3	January 15, 2021
Date BLA/NDA submitted to FDA	April 29, 2022
Year of first approval (global)	2022
Date of first US approval	December 22, 2022
INN, US product name	Mosunetuzumab, mosunetuzumab-axgb
US or EU approved indications	US: First approval for Follicular Lymphoma (LUNSUMIO is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy) (as of first label and as of December 22, 2024 label.). EU: First approval for Follicular Lymphoma (LUNSUMIO as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies) (as per EPAR - Product Information last updated on October 22, 2024).

Company information

Company	Genentech
Licensee/Partner	Biogen
Comments about company or candidate	Mar 2024: Chugai submits marketing application in Japan. https://www.chugai-pharm.co.jp/english/news/detail/20240314150001_1055.html?year=2024&category= Dec 22, 2022: Genentech announces FDA approval. July 5, 2022: Genentech announced that the U.S. Food and Drug Administration has accepted the company’s Biologics License Application (BLA) and granted Priority Review for mosunetuzumab, a potential first-in-class CD20xCD3 T-cell engaging bispecific antibody, for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least two prior systemic therapies. FL is the most common indolent (slow growing) form of non-Hodgkin’s lymphoma (NHL), a type of blood cancer, which often returns after initial therapy. PDUFA date is December 29, 2022. June 8, 2022: Roche announced that the European Commission has granted conditional marketing authorisation for the CD20xCD3 T-cell engaging bispecific antibody Lunsumio® (mosunetuzumab), for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least two prior systemic therapies. Approval is based on the phase I/II GO29781 study, where Lunsumio induced high complete response rates, with the majority of complete responses lasting for at least 18 months in people with heavily pre-treated FL April 22, 2022: Positivie opinion from CHMP announced. Feb. 01, 2022: Biogen Inc. announced that it exercised its option to participate in the development and commercialization of mosunetuzumab. EMA started application review Oct 28, 2021. NCT04712097 Phase 3 in follicular lymphoma as of Roche H1 2021 update. Plan 2021 BLA (https://www.roche.com/dam/jcr:a1437516-3f73-4112-a483-40c8b1c3836e/en/irp210722.pdf) July 2020: Roche announced that its investigational CD20xCD3 T-cell engaging bispecific mosunetuzumab has been granted Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma who have received at least two prior systemic therapies. NCT04246086 study started in Aug 2020 is a Phase 1 study in FL; asset is listed as having a new pivotal trial start in 2020 in Roche update of Sep 2020. NCT03677154 Phase 1/2 study started in May 2019. Two Phase 1/2 studies started in Oct 2018. Listed in Genentech pipeline, NCT02500407 Phase 1 study still recruiting patients as of Aug 2018. Included as Phase 1 in Q3 2015 update
Full address of company	South San Francisco, California, United States North America United States of America https://www.gene.com/contact-us/visit-us

Description/comment

N297G mutation results in aglycosylated Fc. IgG assembled from half-antibodies (KiH). RG7828 (anti-CD20/CD3) is a full-length bisepcific antibody that targets CD20 on B cells and CD3 on T cells. It has a mode of action distinct from other CD20-directed antibody therapies, in that it is designed to recruit and activate cytotoxic T cells to kill malignant B cells. Described as "full-length, humanized immunoglobulin G1 molecule with near-native antibody architecture constructed using "knobs-into-holes" technology." in Sci Transl Med. 2015 May 13;7(287):287ra70. doi: 10.1126/scitranslmed.aaa4802

Additional information

Anticipated events	Regulatory review in Japan, China
Factor(s) contributing to discontinuation	None