Merck and GE Healthcare collaborate on use of imaging biomarkers for investigational BACE inhibitor clinical development program

Merck (NYSE: MRK), known as MSD outside the United States and Canada, and GE Healthcare today announced a clinical study collaboration, license and supply agreement for use of [18F]Flutemetamol, an investigational positron emission tomography (PET) imaging agent, to support Merck’s development of MK-8931, a novel oral beta amyloid precursor protein site cleaving enzyme (BACE) inhibitor and Merck’s lead investigational candidate for Alzheimer’s disease (AD).

Accumulation of beta amyloid in the brain is a pathological characteristic related to Alzheimer’s disease. Currently, AD is diagnosed by clinical examination (i.e., medical history, physical, neurological, psychiatric and neuropsychological exams, laboratory tests and Magnetic Resonance Imaging [MRI] or Computed Tomography [CT] scan). An AD diagnosis can only be confirmed through histopathological identification of characteristic features, including beta amyloid plaques, in post-mortem brain samples.

“There is a serious unmet need for a reliable method for measuring beta amyloid deposits to help physicians diagnose Alzheimer’s disease at its different stages and study its progression,” said Darryle Schoepp, Ph.D., senior vice president, head of neuroscience and ophthalmology, Merck Research Laboratories. “This agreement will allow us to employ an investigational imaging agent to help identify patients who might benefit from an anti-amyloid therapy and enable clinical evaluation of our lead BACE inhibitor candidate for Alzheimer’s disease, MK-8931.”

Under the agreement, GE Healthcare will supply [18F]Flutemetamol to help select patients for clinical trials and evaluate this investigational agent as a companion diagnostic tool. A joint Merck and GE Healthcare Imaging Advisory Committee will oversee the planned imaging studies.

“In clinical trials, [18F]Flutemetamol demonstrated consistent performance in the visual detection of beta amyloid in the brain when compared with histopathology data,” said Jonathan Allis, general manager, PET, GE Healthcare Medical Diagnostics. “[18F]Flutemetamol imaging has the potential to be part of a larger diagnostic workup that may help doctors rule out Alzheimer’s disease by reliably showing the absence of amyloid deposits in patients with unexplained loss of cognitive function.”

About Merck’s BACE Inhibitor Development Program and MK-8931

Merck is advancing several innovative programs in Alzheimer’s disease, including candidates designed to modify disease progression as well as improve symptom control. Merck’s lead candidate in disease modification is MK-8931, an investigational oral BACE inhibitor.

Results of Phase I clinical studies demonstrated that MK-8931 can reduce cerebral spinal fluid (CSF) beta amyloid by greater than 90 percent in healthy volunteers without dose limiting side effects. Based on these results, Merck is moving forward with a global, multi-center Phase II/III clinical trial, called EPOCH, to evaluate the safety and efficacy of MK-8931 versus placebo in patients with mild-to-moderate AD. For more information about the EPOCH study please visit www.ADstudyinfo.com or call 1-855-55-EPOCH (37624). Information is also available at www.clinicaltrials.gov.

About [18F]Flutemetamol

[18F]Flutemetamol is an investigational PET imaging agent being developed by GE Healthcare for the detection of beta amyloid deposits in the brain. Pooled results from Phase III brain autopsy and biopsy studies showed a strong concordance between [18F]Flutemetamol images and AD-associated beta amyloid brain pathology. Phase III studies demonstrated [18F]Flutemetamol visual detection of beta amyloid with a majority read sensitivity of 86 percent and specificity of 92 percent.

About Alzheimer’s Disease and Amyloid Hypothesis

Alzheimer’s disease (AD) is a devastating, irreversible and ultimately fatal disease that progressively destroys neurons in the brain, leading to a deterioration of cognitive function. The symptoms include loss of memory that progresses into behavioral changes, alterations in thinking and reasoning skills that interfere with daily activities, and dementia. AD is the most common cause of dementia, accounting for approximately 50-75 percent of the estimated 35 million dementia cases globally.1,2 About 5.4 million people in the United States are currently living with AD.3 There are currently no disease-modifying treatments available for AD, and current treatment options are limited to providing symptomatic improvements with only modest and short-term effects.

While the exact cause of AD remains unknown, a current prevailing theory asserts that AD occurs due to the accumulation of beta amyloid proteins in the brain. Beta amyloid precursor protein site cleaving enzyme (BACE) is believed to be a key enzyme in the production of beta amyloid peptide. Evidence suggests that inhibiting BACE decreases the production of beta amyloid and may therefore reduce amyloid plaque formation and modify disease progression.

References

1. Alzheimer’s Disease International. Types of Dementia: Alzheimer’s Disease. Available at: http://www.alz.co.uk/info/alzheimers-disease.
2. Alzheimer’s Disease International. Dementia Statistics. Available at: http://www.alz.co.uk/research/statistics.
3. Alzheimer’s Association. Alzheimer’s Fact and Figures. Available at: http://www.alz.org/alzheimers_disease_facts_and_figures.asp