Sunlenca: genotox, carcinogenicity and repro: done or skipped?

“Lenacapavir was negative for mutagenesis in the in vitro reverse mutation assay, negative for clastogenicity in the in vitro assay using human peripheral lymphocytes, and negative for genotoxicity in the in vivo micronucleus assay in rats.”

“A treatment-related increase in the incidence of malignant sarcoma at the injection site was observed in males and a treatment-related increase in combined benign fibroma and malignant fibrosarcoma at the injection site was observed in females, at the highest dose (927 mg/kg).”

“In animal reproduction studies, no adverse developmental effects were observed when lenacapavir was administered to rats and rabbits at exposures (AUC) ≥16 times the exposure in humans at the recommended human dose (RHD) of SUNLENCA”

“As no adverse cardiovascular effects were observed in dogs at exposures 20-fold the clinical free Cmax and a human thorough QT study without significant effects at supratherapeutic doses of lenacapavir is available, the lack of a hERG study is however considered acceptable.”

“Lenacapavir was negative for mutagenesis in the in vitro reverse mutation assay, negative for clastogenicity in the in vitro assay using human peripheral lymphocytes, and negative for genotoxicity in the in vivo micronucleus assay in rats.”

“Lenacapavir was negative for mutagenesis in the in vitro reverse mutation assay, negative for clastogenicity in the in vitro assay using human peripheral lymphocytes, and negative for genotoxicity in the in vivo micronucleus assay in rats.”

“Lenacapavir was negative for mutagenesis in the in vitro reverse mutation assay, negative for clastogenicity in the in vitro assay using human peripheral lymphocytes, and negative for genotoxicity in the in vivo micronucleus assay in rats.”

“The carcinogenicity potential of lenacapavir is being evaluated in a 26-week study (single subcutaneous injection given once every 13 weeks for a total of two doses) in 001178-T (hemizygous) RasH2 mice and a 2-year study (single subcutaneous injection given once every 13 weeks for a total of eight doses) in Wister Hanover rats.”

“A 6-month transgenic mouse (TgRasH2) and a 2-year rat carcinogenicity studies with lenacapavir are stated to be in progress becoming available between end of 2021 and early 2023).”

“As lenacapavir became a suspension at concentrations ≥ 0.1 µM in the DMSO/buffer vehicle used for the patch clamp technique no GLP hERG assay was performed.”