Table II.

Summary of dOFM and Biopsy Data With Selected Background Information

Drug	MW [Da]	cLogP	Fu*	dOFM avg [nM]	dISFtot avg [nM]	dISFu avg [nM]	Biopsy upper dermis [μM]	Biopsy lower dermis [μM]	Main evidence of clinical efficacy
Diclofenac 2%	296	4.3	0.01	31.0	301	3.0	74.8	2.5	Rx osteoarthritis pain [46]
Crisaborole 2%	251	2.6	0.04	11.2	99	4.2	29.2	2.5	Rx atopic dermatitis [47]
Brepocitinib 3%	389	1.6	0.68	3.1	10	6.9	12.8	1.3	Atopic dermatitis Ph2 [48]
Ruxolitinib 1.5%	306	2.5	0.16	1.6	10	1.7	n.a	n.a	Rx atopic dermatitis and vitiligo [49]
Tofacitinib 2%	312	1.5	0.75	1.4	4.3	3.3	2.9	0.2	Atopic dermatitis Ph2 [50]
PF-06763809 2.3%	498	3.8	0.05	0.2	1.8	0.1	3.1	0.2	Failed psoriasis plaque test [51]
PF-06263276 4%	567	~ 4.0	~ 0.001	0.1	1.1	0.001	2.9	0.2	Failed psoriasis plaque test [52]

Fu* refers to the fraction of unbound drug assessed by rapid equilibrium dialysis (RED) in dOFM samples from pigs. The data for all drugs in Study#1 are shown. Ruxolitinib was added from Study#2 (no biopsies). The drugs from Pfizer and their clinical efficacies were blinded until finalization of data analysis. Concentration data are geometric means (dISFtot/dISFu average 0–8 h: N = 12 profiles for brepocitinib, N = 6 profiles for others; biopsies at 8 h: N = 36 for brepocitinib, N = 18 for others). Bold letters indicate dISF concentrations which are considered most relevant for local drug efficacy. Note: dISFu concentrations are from lower dermis thus representing an underestimate of the concentrations in the upper dermis and epidermis.