<p>The disease-modifying monoclonal antibodies lecanemab and donanemab have demonstrated efficacy in slowing clinical decline in early-stage Alzheimer’s disease (AD), bringing practical questions about formulation and delivery to the forefront. With a new weekly subcutaneous (SC) option for lecanemab, clinicians and patients can weigh the advantages of clinic oversight against home convenience, with pipeline advances likely to make shared decisions about drug administration increasingly important.</p>

The currently US Food and Drug Administration (FDA)–approved disease-modifying therapies (DMTs) for the treatment of early-stage AD, lecanemab and donanemab, are amyloid-β–directed monoclonal antibodies that are changing the course of the disease by affecting the underlying biology rather than by treating symptoms.

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In January 2023, lecanemab was granted accelerated approval from the FDA for mild cognitive impairment (MCI) or mild Alzheimer’s dementia based on the findings from the phase 3, randomized, placebo-controlled Clarity AD trial. In addition to the findings of reduced amyloid-β burden 18 months post treatment in study participants with early-stage AD, Clarity AD also demonstrated that participants in the lecanemab arm had significantly less cognitive and functional decline vs patients who received placebo.

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In July 2024, the FDA approved donanemab for the treatment of patients with AD who have MCI or mild Alzheimer’s dementia based on the results from the phase 3 TRAILBLAZER-ALZ 2 trial. TRAILBLAZER-ALZ 2 showed that, among patients with early symptomatic AD and amyloid and tau pathology, donanemab significantly slowed clinical progression.

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With the efficacy established, the next practical considerations relate to how each drug is formulated and delivered, as the route of administration often determines who can receive therapy, how reliably they can continue it, and how practices operationalize monitoring. So, what does the administration look like in practice, and what burdens does it introduce?

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Lecanemab and donanemab were both initially approved by the FDA as intravenous (IV) formulations. IV administration offers advantages, as it occurs under direct clinical supervision, which simplifies drug reaction management, vital sign monitoring, and rapid escalation if new neurologic symptoms raise concern for such conditions as amyloid-related imaging abnormalities. The administration of infusions by clinical staff ensures dose accuracy and documentation, and many infusion centers can coordinate magnetic resonance imaging monitoring around infusion visits. From a formulation standpoint, this means that both agents begin their life cycles in most health systems as clinic-based IV therapies delivered on a recurring schedule, leveraging existing infusion infrastructure and standardized treatment protocols.

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The trade-offs of IV administration include recurring travel and chair time burden, a required period of postinfusion observation, and a dependence on infusion center capacity. These burdens may disproportionately affect patients who have limitations with transportation and/or caregiver availability. In short, the IV formulation concentrates on proper administration and safety oversight in the clinic, but there is burden there as well.

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Recently, lecanemab’s maintenance-phase dosing option has expanded with the FDA’s recent approval of a once-weekly SC autoinjector formulation for use after the completion of an initial 18-month IV course of lecanemab. A recent study presented at the Alzheimer’s Association International Conference 2025 showed that the SC formulation of lecanemab has a safety and tolerability profile that favorably compares with the FDA-approved 10-mg/kg biweekly IV dose. Moreover, there were no differences in clinical outcomes between continued biweekly IV dosing and 360-mg weekly SC maintenance dosing. This introduces a clear formulation distinction between lecanemab and donanemab; lecanemab now offers an IV-to-SC pathway, whereas donanemab remains IV only.

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In addition to increasing the dosing choices for patients, the FDA approval of the new SC formulation of lecanemab comes with potentially different benefits that are not realized with the IV formulation. Among the perhaps most obvious benefits of SC dosing include reduced patient reliance on infusion center appointments, potential decreases in travel and caregiver time, and the flexibility to align dosing with household routines. Having the option of maintenance dosing outside of infusion centers may relieve capacity constraints, allow dosing that is independent of infusion chair schedules, and help to facilitate care for patients who live far away from infusion centers.

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Naturally, success with SC dosing may depend on various factors that are not as important with IV dosing, including consistent patient or caregiver participation; the training of patients to prevent dose handling errors; attention to storage, timing, and documentation; and follow-up outside a traditional infusion center. Importantly, a recent human factors validation study showed that most intended users of the SC formulation of lecanemab, including patients with MCI or mild AD, caregivers, and clinicians, successfully administered full doses under expected-use conditions, underscoring that these challenges may be manageable with standardized training and oversight. Thus, for lecanemab, specifically, the SC formulation appears implementable in real-world settings with structured training, whereas donanemab’s current IV-only formulation keeps the administration and many of the logistics infusion center based.

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We can expect that advances will continue in the development of these currently available DMTs. For SC lecanemab, a 500-mg dose is being developed and investigated for use as a starting dose in early-stage AD. The manufacturers of donanemab may also develop an SC formulation, as evidenced by a 2021 study report. Several other DMTs for AD with different routes of administration are also being developed and, if FDA approved, will further increase the number of available treatment options.

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For clinicians and patients, then, “which drug?” is increasingly becoming “which formulation, at which phase, and for which person?” Clinic-based oversight (eg, IV formulations) has to be balanced against potential home-based convenience (eg, SC formulations). As the DMT pipeline matures, shared decision making that explicitly addresses formulation preferences, alongside efficacy, safety, monitoring, coverage, and caregiver bandwidth, will likely be central to durable, real-world benefits.