Developing a solid BACE

WHITEHOUSE STATION, N.J.—In an effort to better supportpatient selection for the clinical development of MK-8931, Merck & Co.'slead investigational medicine for Alzheimer's disease, the company—which isknown as MSD outside the United States and Canada—has signed a collaborationdeal with Austin, Texas-based Luminex Corp.

Specifically, the deal calls for Luminex to be responsiblefor development, regulatory submission and commercialization of the candidatecompanion diagnostic device to help screen patients for recruitment into Merck'sclinical development program for MK-8931, a novel oral beta amyloid precursorprotein site cleaving enzyme (BACE) inhibitor.

The device will build off Luminex's xMAP technology, withthe goal of measuring concentrations of two candidate biomarkers, Aβ42 andt-tau, in cerebrospinal fluid samples from patients with mild cognitive impairment.The candidate device will be evaluated as a means to identify subjects withmild cognitive impairment who have a higher risk of developing Alzheimer's asMerck selects patients for its BACE inhibitor clinical program.

According to Dr. Darryle D. Schoepp, senior vice presidentand head of the Neuroscience and Ophthalmology division at Merck ResearchLaboratories, "Evaluation of biomarkers that may provide an indicator ofdisease onset and enable earlier diagnosis is an important goal toward facilitatingearly intervention and potentially improving the treatment of Alzheimer'sdisease." And, as he notes, recent clinical evidence supports the hypothesisthat the measurement of the investigational biomarkers Aβ42 and t-tau incerebrospinal fluid may be useful in identifying patients at greater risk ofdeveloping Alzheimer's disease, which currently is diagnosed by clinicalexamination—primarily, medical history; physical, neurological, psychiatric andneuropsychological exams; and magnetic resonance imaging or computed tomographyscans have been used for this purpose.

Patrick J. Balthrop, president and CEO of Luminex, says he looksforward to "leveraging our technologies and development capabilities and …expanding our activity into the companion diagnostic segment of personalizedmedicine" and is confident in the potential for this collaboration to deliver anovel companion diagnostic to identify patients at increased risk of developingAlzheimer's disease.

Zacks Investment Research, which currently gives Merck aZacks Rank #3 (Hold) rating, wrote in an investor's note, "We view MK-8931 as ahigh risk-high return candidate for Merck. The successful development oftherapies for the treatment of Alzheimer's disease is challenging, and we notethat several companies, including Medivation, have failed in developingtreatments for the same."

However, Zacks also concedes that the Alzheimer's diseasemarket represents huge commercial potential and therefore attracts a lot ofinterest.

"A successfully developed product could generate billions ofdollars in sales once launched," Zacks notes. "As per data provided by theAlzheimer's Association, approximately 5.2 million people have Alzheimer'sdisease in the U.S. alone," and adds of Merck: "While headwinds remain in theform of the Singulair genericization, EU pricing pressure, unfavorable currencymovement, U.S. healthcare reform and pipeline setbacks, some of the company'srecent launches should start contributing significantly to the top line in theforthcoming quarters."

Financial terms for the Merck-Luminex deal were notdisclosed.

In related news, Merck and GE Healthcare in December 2012announced a clinical study collaboration, license and supply agreement for useof [18F]Flutemetamol, an investigational positron emission tomography imagingagent, to support development of MK-8931.

Merck is advancing what it calls "several innovativeprograms" in Alzheimer's disease, including candidates designed to modifydisease progression as well as improve symptom control. As for its leadcandidate in disease modification, MK-8931, results of Phase I clinical studiesof the BACE inhibitor reportedly have demonstrated that MK-8931 can reducelevels of beta amyloid in cerebrospinal fluid by greater than 90 percent inhealthy volunteers and people with Alzheimer's disease without dose-limitingside effects.

Based on these results, Merck is conducting a global,multi-center Phase II/III clinical trial, EPOCH, to evaluate the safety andefficacy of MK-8931 versus placebo in patients with mild-to-moderateAlzheimer's and has plans to initiate a trial in prodromal subjects.

In addition to the xMAP pen-architecture multi-analyteplatform, the proprietary instruments and assays at Luminex include MultiCodereal-time polymerase chain reaction (PCR) and multiplex PCR-based technologiesthat, as the company maintains, "deliver cost-effective rapid results to cliniciansand researchers."