PF-06751979 / Pfizer - LARVOL DELTA

Selective Secretase Targeting for Alzheimer's Disease Therapy. (PubMed, J Alzheimers Dis) - "In this regard, BACE-1 inhibitors, such as Atabecestat, NB-360, Umibecestat, PF-06751979, Verubecestat, LY2886721, Lanabecestat, LY2811376, and Elenbecestat, were submitted to phase I-III clinical trials. Such therapeutic tools shall focus on slowing down or minimizing the progression of neuronal damage. Here, we summarize structures and the activities of the latest compounds designed for AD treatment, with remarkable in vitro, in vivo, and clinical phase activities."

Journal • Review • Alzheimer's Disease • CNS Disorders

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of PF-06751979, a Potent and Selective Oral BACE1 Inhibitor: Results from Phase I Studies in Healthy Adults and Healthy Older Subjects. (PubMed, J Alzheimers Dis) - P1 | "A drug interaction study (NCT03126721) using midazolam indicated that there was no clinically meaningful effect of multiple doses of PF-06751979 100 mg QD on the PK of single-dose midazolam in healthy adults. Overall, these data suggest that PF-06751979 with daily dosing is favorable for further clinical development."

Clinical • Journal • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders

Design and Synthesis of Clinical Candidate PF-06751979: A Potent, Brain Penetrant, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation. (PubMed, J Med Chem) - "Herein we describe the identification of clinical candidate PF-06751979 (64) which displays excellent brain penetration, potent in vivo efficacy, and broad selectivity over related aspartyl proteases including BACE2. Chronic dosing of 64 for up to 9-months in dog did not reveal any observation of hair coat color (pigmentation) changes and suggests a key differentiator over current BACE1 inhibitors that are non-selective against BACE2 in later stage clinical development."

Clinical • Journal