S2 Ep79: Alzheimer Updates, Stroke Breakthroughs, and the Case for Early Treatment

In this episode of Mind the Meds, Erica Marini, PharmD, highlights information from the European Stroke Organization Conference include encouraging data on asundexian
(Bayer), a factor XIa inhibitor showing reduced recurrent ischemic stroke risk without increased bleeding, as well as positive results from three trials of tirofiban in acute ischemic stroke settings. On the multiple sclerosis (MS) front, Marini covers the FDA approval of ocrelizumab (Ocrevus; Genentech) for pediatric relapsing-remitting MS in children 10 and older, a new study supporting early use of high-efficacy agents in pediatric MS, and 2 Lancet publications on ocrelizumab — one examining higher weight-adjusted dosing (which did not improve disability progression) and one confirming benefit in a broader primary progressive MS population. She also briefly discusses PADOVA (NCT04777331), a phase 2b trial of prasinezumab in early Parkinson's disease, which failed to meet its primary end point.
The bulk of the episode is a discussion with guest Millad Sobhanian, PharmD, BCPS, clinical pharmacy specialist in neurology at the University of Maryland, focused on Alzheimer disease. They cover dextromethorphan/bupropion (Auvelity; Axsome Therapeutics), newly approved in April 2026 for agitation associated with Alzheimer dementia. Sobhanian walks through key safety considerations—including additive NMDA antagonism if combined with memantine, cardiovascular risks from the bupropion component, and the ever-present black box warning on antipsychotics in dementia patients—while both note that the efficacy data, though statistically significant, shows modest clinical effect sizes compared to the threshold for meaningful within-patient change.
The conversation then turns to lecanemab's subcutaneous initiation formulation (Leqembi Iqlik; Eisai, Biogen), whose FDA decision has been delayed to about August 2026 as regulators seek more data on bioavailability and ARIA monitoring in the at-home setting. Sobhanian shares his real-world perspective on anti-amyloid therapy, describing a patient population that is typically early-stage, high-functioning, and has a mean age of about 60 to 70 years, and emphasizing the pharmacist's role in expectation-setting around the modest but potentially cumulative slowing of cognitive decline.
The episode closes with a thorough discussion of the April 2026 Cochrane review on amyloid-targeting monoclonal antibodies, which both Marini and Sobhanian find overly broad in its conclusions. They note limitations such as the inclusion of withdrawn agents like aducanumab (Aduhelm; Biogen), heterogeneous inclusion criteria across trials, and an 18-month study horizon that may be too short to capture the full benefit suggested by longer-term open-label extension data.

Key Takeaways:
1. New options for Alzheimer's agitation exist, but fit carefully into the treatment algorithm. Dextromethorphan/bupropion offers a novel NMDA-based mechanism for treating agitation in Alzheimer dementia, but its clinical effect size is modest, and it carries meaningful safety considerations—particularly around the bupropion component in elderly patients. Like all pharmacologic options in this space, it remains a later-line choice after nonpharmacologic interventions have been exhausted, and medication reconciliation is critical given its interaction potential with memantine and CYP2D6 inhibitors.
2. Anti-amyloid therapies are imperfect but not ready to be written off. The April 2026 Cochrane review drew significant attention with its conclusion that anti-amyloid monoclonal antibodies produce only trivial cognitive benefits, but its findings are limited by the inclusion of older, withdrawn agents, heterogeneous trial populations, and an 18-month time horizon that may be too short to capture the full trajectory of benefit.
3. The pharmacist's role in anti-amyloid therapy goes well beyond dispensing. As illustrated by Sobhanian's practice at the University of Maryland, clinical pharmacists embedded in neurology clinics play a critical role in patient selection, expectation-setting, ARIA counseling, and informed decision-making for patients considering anti-amyloid therapy—a complex, high-stakes treatment decision that these patients and their caregivers should never be navigating alone.