ACAD stock: Alzheimer | 48% plunge on March 9, 2021 | My investigation before investment

 Yahoo -> Finance -> Conversation 

Everything considered: IMO this is a patient profile labeling issue

1. There are many types of dementia (Alzheimer's, Lewy body, vascular...).
2. Within each type of dementia there are subgroups: mild, moderate, severe.
3. We know that the FDA has asked for additional data on the PII AD study. This study (see abstract below) showed a pronounced benefit in severe Alzheimer's patients (P less than 0.001). For the entire patient population p=0.045. So the question is what is the p value for the non-severe pt population? Should Nuplazid be prescribed for all ADP pts, or only the subgroup with severe symptoms? I think this is what the FDA wants to clarify.

Worst case interim scenario: CRL followed by refiling in 3 months.
Final outcome: approval for DP; Nuplazid is first-in-class, best-in-class, with Breakthrough Therapy Designation for DP and has very positive support from the medical community.

Clinical Trial J Prev Alzheimers Dis. 2019;6(1):27-33. doi: 10.14283/jpad.2018.30.

Pimavanserin in Alzheimer's Disease Psychosis: Efficacy in Patients with More Pronounced Psychotic Symptoms

C Ballard 1, J M Youakim, B Coate, S Stankovic

PMID: 30569083 DOI: 10.14283/jpad.2018.30
Full text linksCite

Abstract
Background: Pimavanserin is a 5-HT2A receptor inverse agonist/antagonist and is approved in the United States for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.

Objective: Evaluate the efficacy of pimavanserin on symptoms of psychosis in patients with Alzheimer's disease (AD).

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Nursing home residents.

Participants: Patients with AD psychosis.

Interventions: Pimavanserin 34 mg or placebo daily for 12 weeks.

Measurements: The primary endpoint was mean change from baseline at Week 6 on the Neuropsychiatric Inventory-Nursing Home Version psychosis score (NPI-NH-PS). In the prespecified subgroup analysis, the mean change in NPI-NH-PS and the responder rates among those with baseline NPI-NH-PS ≥12 were evaluated.

Results: Of 181 patients randomized (n=90 pimavanserin; n=91 placebo), 57 had baseline NPI-NH-PS ≥12 (n=27 pimavanserin; n=30 placebo). In this severe subgroup, large treatment effects were observed (delta=-4.43, Cohen's d=-0.73, p=0.011), and ≥30% improvement was 88.9% vs. 43.3% (p<0.001) and ≥50% improvement was 77.8% vs. 43.3% (p=0.008) for pimavanserin and placebo, respectively. The rate of adverse events (AEs) in the severe subgroup was similar between treatment groups, and urinary tract infection, fall, and agitation were most frequent. Serious AEs was similar with pimavanserin (17.9%) and placebo (16.7%) with fewer discontinuations due to AEs with pimavanserin (7.1%) compared to placebo (10.0%). Minimal change from baseline occurred for the mean MMSE score over 12 weeks.

Conclusions: Pimavanserin demonstrated significant efficacy in AD psychosis in patients with higher baseline severity of psychotic symptoms (NPI-NH-PS ≥12). Treatment with pimavanserin showed an acceptable tolerability profile.