BIIB118 / Biogen - LARVOL DELTA

Investigation of CYP3A induction by PF-05251749 in early clinical development: comparison of linear slope PBPK prediction and biomarker response. (PubMed, Clin Transl Sci) - "PBPK models were developed to characterize the observed clinical pharmacokinetics (PK) of PF-05251749 at 400 mg QD and 750 mg QD; the PBPK induction model was calibrated using the in vitro linear fit induction slope, with rifampin as reference compound (Ind = 8, EC = 0.32 μM). Clinical trial simulation following co-administration of PF-05251749, 400 mg QD with oral midazolam 2 mg, predicted no significant drug interaction risk...In conclusion, good agreement was obtained between CYP3A drug interaction risk predicted using linear-slope PBPK model and exploratory biomarker trends. This agreement between two orthogonal approaches enabled assessment of drug-interaction risks of PF-05251749 in early clinical development, in the absence of a clinical DDI study."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Assumption Checking Before Application of the Prespecified QT Linear Mixed Effect Model is Essential. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "In the paper, titled Evaluation of QT Liability for PF-05251749 in the Presence of Potential Circadian Rhythm Modification , the authors presented results from assessment of QT-liability based on (i) clinical data and (ii) simulations using models for a drug that affects QT circadian rhythm."

Journal

Biogen reports full year 2019 revenues of $14.4 billion (Biogen Press Release) - "Biogen Inc....today reported full year and fourth quarter 2019 financial results...'We are excited about the prospects for aducanumab in Alzheimer’s disease and look forward to completing a regulatory filing in the U.S. as soon as possible'....R&D expense in the fourth quarter of 2019 included $45 million related...to develop and commercialize BIIB080, an antisense oligonucleotide targeting tau, for Alzheimer’s disease and potentially other tauopathies....In January 2020 Biogen announced an agreement to acquire from Pfizer PF-05251749...This transaction...is expected to close in the first quarter of 2020."

Commercial • Licensing / partnership • Regulatory

Biogen to Acquire Novel Clinical Stage Asset with Application in Alzheimer’s Disease and Parkinson’s Disease from Pfizer Inc. (GlobeNewswire, Biogen Inc.) - "Biogen Inc….today announced an agreement to acquire from Pfizer Inc….PF-05251749, a novel CNS-penetrant small molecule inhibitor of casein kinase 1 (CK1)…Biogen plans to develop the Phase 1 asset for the treatment of Sundowning in Alzheimer’s disease (AD) and Irregular Sleep Wake Rhythm Disorder (ISWRD) in Parkinson’s disease (PD). The purchase will include an upfront payment of $75 million with up to $635 million in potential additional development and commercialization milestone payments...Biogen aims to initiate a Phase 1b study in Q4 2020."

Licensing / partnership • New P1 trial

Evaluation of QTc liability for PF-05251749 in the presence of potential circadian rhythm modification. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "However, simulation results indicated that inference of drug-induced QTc prolongation could be misleading if drug effect on QTc circadian rhythm is not properly addressed. The modeling and simulation results suggest that pre-specification of the concentration-QTc model should be reconsidered for drugs with circadian rhythm modulation potential."

Journal