Biogen Acquiring Pfizer’s Investigational Therapy PF-05251749 for Alzheimer’s, Parkinson’s Symptoms

Biogen is acquiring from Pfizer investigational therapy PF-05251749, a small molecule being developed to treat sundowning in Alzheimer’s disease and irregular sleep wake rhythm disorder (ISWRD) in Parkinson’s disease.

The company plans to begin a Phase 1b clinical trial by the end of this year, according to a press release.

PF-05251749 is aimed at regulating circadian rhythms, the changes the body goes through over the course of a day. The body’s internal timekeeping systems help regulate the daily cycles that signal, for example, hunger and sleepiness.

In people with neurological conditions such as Alzheimer’s and Parkinson’s, these systems can become disrupted, with far-reaching consequences.

“Many patients with Alzheimer’s and Parkinson’s suffer from debilitating sleep disorders and agitation, and we believe that the regulation of the circadian rhythm may hold promise in addressing these challenging behavioral and neurological symptoms,” Alfred Sandrock Jr., MD, PhD, Biogen’s executive vice president of research and development and chief medical officer, said in the release.

About a fifth of people with Alzheimer’s experience a circadian disturbance called sundowning, a state of confusion, anxiety, and/or agitation that sets in late in the day and lasts into the night. Many people with Parkinson’s experience ISWRD, in which sleep becomes fragmented and restless. This typically gets worse as the disease progresses.

Both sundowning and ISWRD are thought to be caused, at least in part, by the disruption of the circadian systems in the body. In mammals, the hypothalamus (a region of the brain) plays a critical part in regulating the body’s internal clock. An enzyme called casein kinase 1 (CK1) is also a key regulator.

CK1 exists in two forms, and PF-05251749 is a highly selective inhibitor of both that can be taken orally. It is thought that by blocking CK1, the therapy could help to regulate the circadian clock in people with Alzheimer’s or Parkinson’s.

The compound was tested in healthy adult volunteers in two Phase 1 trials (NCT02443740 and NCT02691702), both of which were sponsored by Pfizer. PF-05251749 showed an acceptable safety profile in the trials. Data was also collected on how the drug moves through and is processed by the body, in particular with regard to getting into the cerebral spinal fluid, which surrounds the brain and spinal cord.

Under the terms of the agreement, Pfizer will receive an upfront payment of $75 million, with the possibility of additional payments up to $635 million based on future milestones.