On April 22, I published predictions for the ACACIA-HCM trial; the topline results were announced yesterday, May 5. According to the sponsor, both co-primary endpoints met statistical significance.
The pre-readout PoS prediction was 57.2% for "either co-primary reaches p<0.05", giving a Brier contribution of $(0.572 - 1)^2 = 0.18$ and a log score of $-\log(0.572) = 0.56$ nats.
Figure 1 overlays the observed point estimate and 95% CI onto the pre-readout posterior predictive intervals for both co-primary endpoints.
The numerical comparison:
Both observed values sit inside the 50% credible interval, and both observed 95% CIs sit fully inside the predicted 95% CrI. The two z-scores are essentially identical (-0.21, -0.22) — this is mechanical, since the peak VO2 posterior was derived from the KCCQ posterior via the shared standardized mean difference (pVO2_SD/KCCQ_SD = 5/22).
The pre-readout posterior was wider than the realized observed uncertainty: the KCCQ 95% CrI had width 11.8 points, while the observed 95% CI is 5.0 points wide; the peak VO2 95% CrI had width 2.7 mL/kg/min, while the observed 95% CI is 0.88 mL/kg/min. Predictive posteriors should be wider than the realized sampling distribution (predictive variance = trial sampling variance + parameter uncertainty), so a width ratio of 2-3x is qualitatively in line with expectations.
The pre-readout report defined a "success" stock level as a 10% move above CYTK spot, anchored to the April 21, 2026 spot of \$65.80, for a threshold of \$72.38. Risk-neutral probabilities at that level were extracted from the listed options chain via the Breeden-Litzenberger approach:
Realized reaction: On 2026-05-05, CYTK closed at \$77.76, a +18.2% move from the April 21 spot of \$65.80. Intraday range was roughly \$61 (premarket low) to \$93 (intraday high). The stock cleared the \$72.38 threshold by a wide margin and finished the day above it.
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Trying to cut corners to make nonlinear PK model fitting faster
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