Excellent points as always, Sam! Expanding, I think the concern is two-fold. Known known (SBECD nephrotoxicity), which as pointed out is low concern (review jasn.asnjournals.org/content/31/7/1… by @MAdamsick stating differences in SBECD exposure from animal studies and RDV course). 1/n
https://twitter.com/OncIDPharmd/status/1318983947531976704
Known unknown – in renal dysfxn/failure, does accumulation of RDV/metabolites occur and lead to tox (including non-renal tox)? For RDV, primarily cleared by non-renal mechs (esterase hydrolysis), but main metabolite (GS-441524) reliant on renal clearance (49% in urine). 2/n 
GS-441524 can accumulate in renal failure/dysfxn, measured levels in 3 HD patients up to 10-fold higher than phase 1 data (MS to be published soon, will share then). However, objectively levels still low (highest ~1.5 mcg/mL) and toxicodynamic threshold unknown 3/n
Patients tolerated tx well. Also, placebo-controlled data suggest that RDV is a well-tolerated drug. Agree that renal dysfxn/failure shouldn’t alter decision-making, but would encourage measuring/sharing data to improve confidence that tx tolerated in these pts. 4/4
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