AstraZeneca's Kidney Trial Has a 59% Modeled Chance of Success
Jefferies sees a better-than-even chance that AstraZeneca's zibotentan combination clears its Phase 3 kidney trial, but the estimate rests on a narrow efficacy margin and unresolved fluid-retention risk.
Jefferies estimates that AstraZeneca's zibotentan and Farxiga combination has a 59% chance of meeting the main goal of the Phase 3 ZENITH-HP kidney-disease trial. That is a constructive forecast, not a clinical result. The 1,833-patient study is expected to report in the first half of 2027.
ZENITH-HP compares the combination with Farxiga alone in people with chronic kidney disease and high levels of protein in their urine. The main measure is the change in estimated glomerular filtration rate, or eGFR, after two years. Jefferies calculates that the combination needs to preserve roughly 1.1 milliliters per minute per 1.73 square meters more kidney function than Farxiga alone to reach statistical significance.
The bank's combined model produces a median benefit of 1.26 milliliters per minute per 1.73 square meters. Four of its five approaches generate estimates from 0.95 to 1.45, corresponding to modeled success probabilities from 42% to 70%. A more optimistic method based on a small subgroup carries only a 15% weight. That spread matters because the central estimate clears the assumed threshold by just 0.16.
There is biological support for the program. In AstraZeneca's Phase 2b ZENITH-CKD study, the combination reduced urinary albumin more than Farxiga alone after 12 weeks. The low-dose regimen cut albuminuria by 47.7% from baseline, while the high dose produced a 52.5% reduction. Yet the same study highlighted the central safety issue: fluid-retention events occurred in 18.4% of high-dose patients, compared with 8.8% on the low dose and 7.9% on Farxiga alone.
AstraZeneca is using lower zibotentan doses in Phase 3 to limit that risk. Jefferies also flags a possible early eGFR dip, which could weaken the measured two-year benefit even if the drug ultimately protects kidney function.
The commercial stakes are meaningful but still speculative. Jefferies models about $1.3 billion of 2034 sales for a fixed-dose combination, compared with roughly $900 million in consensus estimates, while applying a 60% probability of success. Until the Phase 3 data arrive, the more useful conclusion is narrower: AstraZeneca has a credible efficacy signal, but only modest modeled clearance above the statistical hurdle and a safety trade-off that the lower dose must contain.