Published at time: 2019-12-12 06:28
BioArctic: Greater confidence in BAN2401 after CTAD
We have raised our SOTP-based target price to SEK144 (115) for BAN2401 (early Alzheimer’s disease) on the back of greater confidence in a positive outcome of the recently initiated confirmatory Phase III study CLARITY-AD. We have raised our launch probability estimate for BAN2401 to 55% (45%) on the back of the presentation of detailed aducanumab (Biogen/Eisai) Phase III results from EMERGE and ENGAGE, which were presented at the Clinical Trial in Alzheimer’s Disease (CTAD) meeting in San Diego on 5 December.
Both aducanumab Phase III trials were stopped in March for futility. In October, it was surprisingly announced that a later analysis of the more mature data-set showed that EMERGE met the primary efficacy end-point, while ENGAGE did not. In EMERGE, high-dose aducanumab showed a 23% improvement versus placebo at 18 months on the CDR-SB scale, measuring both cognition and function. In ENGAGE, high-dose aducanumab had a 2% negative effect on CDR-SB. However, a post-hoc analysis of the data, presented at CTAD, showed that the treatment effect of both EMERGE and ENGAGE was consistent in patients enrolled after the PV4 amendment, which enabled a higher dose exposure. In EMERGE, high-dose aducanumab in the post-PV4 population (n=288) showed a 30% improvement in CDR-SB; in ENGAGE (n=282), the improvement was 27% in the post-PV4 population.
The expert panel at CTAD agreed that the treatment effect (~25% improvement over 18 months) is small but still clinically relevant, and that a consistent effect on cognition/function, amyloid plaque and disease biomarkers is evidence of a real disease-modifying effect with aducanumab. For BioArctic’s BAN2401, we see the aducanumab data as supportive of the amyloid hypothesis. Since there is dose titration need with BAN2401 due to the lower risk of side effects (ARIA), drug exposure in the CLARITY-AD study with BAN2401 should be higher. This suggests BAN2401 could show a greater effect size than aducanumab did in EMERGE. We have removed the spinal cord project from the model.