Clesrovimab Regulatory review Naked monospecific

Antibody Information

Entry ID	1015
INN	Clesrovimab
Status	Regulatory review
Drug code(s)	MK-1654
Brand name	(Pending)
mAb sequence source	mAb human
General Molecular Category	Naked monospecific
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)	RSV (F glycoprotein)
Indications of clinical studies	RSV infection
Primary therapeutic area	Infectious diseases

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)	Regulatory review EU, US
Status	Active
Start of clinical phase (IND filing or first Phase 1)	August 30, 2018
Start of Phase 2	October 28, 2019
Start of Phase 3	April 07, 2021
Date BLA/NDA submitted to FDA
Year of first approval (global)	None
Date of first US approval
INN, US product name	None
US or EU approved indications	None

Company information

Company	Merck
Licensee/Partner	None
Comments about company or candidate	December 17, 2024: Merck annouced that the FDA has accepted the BLA for clesrovimab to protect infants from respiratory syncytial virus (RSV) disease during their first RSV season. PDUFA date June 10, 2025. EMA starts Clesrovimab MAA evaluation on Nov 28, 2024. July 2024: Merck announced positive topline results from its Phase 2b/3 clinical trial (MK-1654-004) evaluating clesrovimab (MK-1654), the company’s investigational prophylactic monoclonal antibody designed to protect infants from respiratory syncytial virus (RSV) disease. Regulatory submissions are planned. https://www.businesswire.com/news/home/20240723229019/en/Merck-Announces-Topline-Results-from-Phase-2b3-Trial-of-Clesrovimab-MK-1654-an-Investigational-Respiratory-Syncytial-Virus-Preventative-Monoclonal-Antibody-for-Infants Phase 2/3 (NCT04767373) and Phase 3 (NCT04938830) studies for Reduction in incidence of respiratory syncytial virus infection are recruiting as of May 26, 2023 Listed as Phase 3 asset in Merck pipeline dated Feb 2023. NCT04938830 Phase 3 study started in Nov 2021. NCT04767373 Phase 2/3 study in Healthy Pre-Term and Full-Term Infants started in April 2021. NCT04086472 Phase 2 study started in Oct 2019. NCT03524118, which changed to Phase 1/2 at some point, is still recruiting as of last record update in Aug 2019. Phase 1 NCT03524118 is A Double-blind, Randomized, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-1654 in Pre-Term and Full-Term Infants started in Sep 2018. In a Phase 1 study, MK-1654 was generally well tolerated at doses up to 300 mg IM and up to 3000 mg IV and resulted in a dose dependent increase in SNA titers, reflecting biologically active MK-1654 in the serum. No treatment emergent ADAs have been observed. (https://idsa.confex.com/idsa/2018/webprogram/Paper71974.html)
Full address of company	Rahway, NJ 07065 USA North America United States of America https://www.merck.com/contact-us/

Description/comment

MK-1654 is a fully human monoclonal antibody targeting the RSV fusion (F) protein with Fc domain mutations to extend half-life that is being developed to provide passive immunity against RSV in infants. Incorporation of YTE mutations extend its half-life to allow for dosing once every RSV season. Preferentially targets the prefusion F protein over the postfusion one, according to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742648/

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None