Replies to post #194308 on Biotech Values

[dewophile]

FGEN

they never tested the higher doses - from the paper:

After 35 patients had been enrolled, 18 into the PK/PD cohort (11 to roxadustat, 6 to placebo and 1 untreated) and 17 into the treatment cohort (13 on roxadustat and 4 to placebo), the study was interrupted and then resumed under an amended protocol with removal of PK-only cohorts that were initially planned to be tested (2.5, 3, 3.5 and 4.0 mg/kg) to avoid excessive rate of rise in Hb levels, so subjects enrolled subsequent to this protocol amendment were all ‘treatment subjects’ (screening Hb = 11 g/dL), while a small subset of these patients at selected study sites could also participate in the PK/PD substudy. An additional 82 treatment subjects were enrolled (64 to roxadustat and 18 to placebo). Thus, there were a total of 99 treatment subjects randomized to one of four dose cohorts (1, 1.5, 2.0 or 0.7 mg/kg, BIW versus TIW or to placebo) as detailed in Supplementary Information and Supplementary Figure 1. Treatment subjects are included in the efficacy analyses, and all subjects from the PK and treatment cohorts are included in the safety analyses.

There's not much in the paper frankly, but feel free to email me (DD has my address) if you want a copy. We all know efficacy is a given for roxa, so here's the safety table, but #s are small so make of it what you will (there are additinal ph2 data that i woudl expect to be published that may be more meaningful, for example the incident dialysis ph2 trial):

Table 3.
AEs reported in three or more subjects

Number of subjects with TEAEa, n (%)
Roxadustat (n = 88) Placebo (n = 28)
Any TEAE52 (59.1) 13 (46.4)
Diarrhea 8 (9.1) 2 (7.1)
Headache 6 (6.8) 1 (3.6)
Back pain 4 (4.5) 1 (3.6)
Fatigue 4 (4.5) 0
Hyperkalemia 4 (4.5) 0
Peripheral edema 3 (3.4) 0
Dizziness 2 (2.3) 2 (7.1)
Insomnia 2 (2.3) 1 (3.6)
Seasonal allergy 1 (1.1) 2 (7.1)
Urinary tract infection (UTI)b 1 (1.1) 3 (10.7)

clark - you raised valid concern re hepcidin and infection - UTI was more common in placebo fwiw
odd that fatigue more common in tx arm, but other symptom c/w anemia more common in placebo (dizziness). again #s small so i don't think we cna draw meaningful conclusions on safety from this paper alone. I fully expect QOL measures to be better in tx arm vs placebo in ph3