Months after trial setbacks, Merck licenses Teijin Alzheimer’s candidate

The failure of Merck's BACE inhibitor came after it failed to move the needle in a trial of 2,000 patients with mild-to-moderate Alzheimer’s, delivering another blow to the amyloid hypothesis.

After halting a mid-to-late-stage trial of its doomed-to-fail BACE inhibitor three months ago, Merck has today penned a new licensing deal with Tokyo’s Teijin Pharma for its investigational tau-targeting antibody candidate in Alzheimer’s.

While it has been fast-charging in cancer, racking up a slew of approval and trial wins for its checkpoint inhibitor Keytruda, it has also, like nearly everyone in biopharma for the last decade, posted poor results for its Alzheimer tests.

Back in February, the U.S. big pharma halted a phase 2/3 Alzheimer’s disease trial for verubecestat after an interim analysis found it was destined to fail.

The failure of the BACE inhibitor came after it failed to move the needle in a trial of 2,000 patients with mild-to-moderate Alzheimer’s, delivering another blow to the amyloid hypothesis.

For its latest deal, Merck has in fact turned away from amyloid, which is believed to cause sticky plaques to build up in the brain, to tau. This tau theory associates the onset of the disease to fibrillary tangles called tau protein. Neurofibrillary tangles group in an insoluble form in neurons, affecting normal neuronal functions.

So-called “tauists” are attempting to target and block tau hyperphosphorylation in Alzheimer’s patients in hopes of relieving the negative consequences of the disease.

Its new antibody deal sees Merck gain exclusive, worldwide rights to develop, manufacture and commercialize the candidate.

In exchange, Merck will make an upfront payment to Teijin Pharma (although dollar terms were not published), who is also in-line for future biobucks. Teijin, in addition, retains an option to copromote an approved product in Japan.

“Securing alliances with leading industry partners is a key part of The Teijin Group strategy,” said Akihisa Nabeshima, president of Teijin Pharma. “Teijin Pharma believes that Merck’s strong neuroscience expertise makes it well suited to maximize the potential of this candidate.”

“Teijin Pharma scientists have made important progress to advance this investigational antitau antibody to this stage of development,” added Darryle Schoepp, vice president of neuroscience discovery at Merck Research Laboratories.

“Merck remains committed to developing meaningful therapeutic options for the treatment of Alzheimer’s and other neurological diseases.”

Merck is already working on [18F]-MK-6240, a tau ligand being looked at as a potential PET imaging agent. While it pulled the plug on verubecestat (a.k.a. MK-8931) a few months back, it is also still being tested in a phase 3 study of people with prodromal forms of Alzheimer’s.

But the likelihood of success is slim, if history is anything to go by. The failure rate for Alzheimer’s over the past decade has been a staggering 99%—for a disease that affects an estimated 5.4 million Americans and will eventually prove fatal.

Big Pharmas, including Eli Lilly, AstraZeneca, Biogen, Johnson & Johnson and Pfizer, have all thrown billions of dollars at this research area, but in return have been beset by failures and setbacks, with many now looking to restrict their spending on an area that yields so little ROI.

While medications are on the market for the disease, such as Pfizer/Eisai’s Aricept (donepezil) and others (as well as generics), these have no long-term curative effect and are described by physicians as merely “lifting the fog” for a few weeks or months, only for the disease to come back with a vengeance.

It remains, therefore, a potential major blockbuster market for anyone who can help stop or even reverse the disease.