Sunlenca: what flexibility did regulators accept, and why?

“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.”

“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.”

“It should be noted that the toxicological programme has in most cases not been conducted with the exact clinical formulations - especially the SC formulation (lenacapavir sodium 26.46% [w/w], PEG300 50.13% [w/w] and water) where several variations have been used in the toxicological studies (containing variations of combinations of PEG200, PEG300, P188, ethanol and/or NaOH).”

“This is considered a weakness but still acceptable as all SC exposure independent of exact formulation generated more or less the same toxicity findings.”

“With regard to the DART studies, the choice of conducting repeated oral exposure in rat (which has low bioavailability) and IV exposure in rabbit means that, in practice, a setup where only one animal model has achieved a higher systemic exposure (i.e., rabbit).”

“It is agreed that the there is an absence of adverse DART signals.”