Ionis Pharma Initiates Clinical Study of IONIS-MAPT Rx in Patients with Alzheimer’s Disease

Ionis Pharmaceuticals, Inc. announced that it has initiated a Phase 1/2a clinical study of IONIS-MAPTRx in patients with mild Alzheimer’s disease (AD). Ionis earned a $10 million milestone payment from Biogen related to the initiation of this study.

IONIS-MAPTRx is an antisense drug designed to selectively reduce the production of microtubule-associated protein tau (MAPT), or tau protein, in the brain. Tau misfolding leads to the accumulation of neurofibrillary tangles inside brain cells. These tangles are a hallmark feature of a spectrum of neurodegenerative diseases known as tauopathies, which include AD and some forms of frontotemporal dementia (FTD). AD is the most common form of dementia, accounting for an estimated 70% of cases. FTD is a rare form of early-onset dementia resulting from neuronal damage in the frontal and temporal lobes of the brain.

“In contrast to amyloid plaques that may begin to deposit in the brain for up to 20 years before the onset of AD, tau deposits are spatially and temporally associated with the brain regions where atrophy occurs and neurocognitive deficits originate. IONIS-MAPTRx is designed to reduce the production of all of the many forms of tau in all regions of the brain,” said C. Frank Bennett, Ph.D., senior vice president of research at Ionis Pharmaceuticals.

The three-month randomized, placebo-controlled, dose escalation Phase 1/2a clinical study will evaluate the safety and activity of IONIS-MAPTRx in approximately 44 patients with mild AD. In the study, IONIS-MAPTRx is administered as a once-monthly intrathecal injection directly into the cerebral spinal fluid, similar to the way SPINRAZA® (nusinersen) is administered.  Biogen has an option to develop and commercialize IONIS-MAPTRx.

“IONIS-MAPTRx is another exciting program within our strategic collaboration with Biogen,” said B. Lynne Parshall, chief operating officer of Ionis Pharmaceuticals. “Targeting MAPT represents a unique opportunity to address the unmet need in both rare and more prevalent tauopathies. The first clinical study with IONIS-MAPTRx is in patients with AD, however, in parallel, we also plan to develop IONIS-MAPTRx for patients with FTD, a rare disease population. This strategy has the potential to accelerate the drug’s path to market.”