Eli Lilly’s Kisunla Bags FDA Green Light For Alzheimer’s Drug’s New Dosing

The benefit-risk ratio looks like it increasingly favours Eli Lilly’s Kisunla in early Alzheimer’s disease, following the FDA’s approval of a new dose plan with an enhanced safety profile.

The revised protocol for Kisunla includes a more progressive titration and a markedly reduced incidence of brain swelling, referred to as amyloid-related imaging abnormalities with oedema and effusion (ARIA-E), in comparison to the initial regimen.

ARIA is a pervasive side effect that has hindered the widespread application of anti-amyloid antibody medicines, such as Kisunla, in the early stages of Alzheimer’s disease.

Brandy Matthews, M.D., Lilly’s VP of Global and U.S. Medical Affairs for Alzheimer’s disease, stated in an interview that any progress made in advancing scientific understanding in this area is likely to influence the conversations clinicians have with patients regarding the balance of benefits and risks.

The initial Kisunla prescription administers two 350 mg vials of the medication for every one of the first three infusions, then raising to four units from the fourth dosage onwards. The revised dosing protocol commences with one vial for the initial infusion, then moves onto two vials for the subsequent infusion, three vials for the next, and four vials for each dose afterward. The medication is to be taken every four weeks.

In the phase 3b research designated Trailblazer-Alz6, the altered Kisunla regimen considerably reduced the incidence of any ARIA-E to 14%, in contrast to 24% for participants taking the original regimen, by week 24. This corresponds to a 41% reduction in risk for the new dose schedule.

In the first year, the ARIA-E rate for the two doses was 16% and 25% respectively, with the modified dose showing a 35% risk reduction.

The adjusted titration group also saw a reduced incidence of severe ARIA-E episodes. None of the individuals who got the adjusted regimen developed radiographically significant ARIA-E. In contrast, the first treatment in the phase 3 Trailblazer-Alz2 research, which supported Kisunla’s FDA approval for early symptomatic Alzheimer’s, recorded two cases of comparable severity, as observed by Matthews.

The revised dosing schedule reduced ARIA-E occurrences without diminishing the drug’s efficacy in decreasing amyloid levels. At 24 weeks, participants on the adjusted titration regimen exhibited an average reduction of 67% in amyloid plaques relative to baseline, whereas those on the original dosage regimen demonstrated a 69% reduction, as indicated by Trailblazer-Alz6.

Matthews noted that the study’s findings could offer meaningful and favorable implications for both medical professionals and patients as they navigate discussions about the benefits and risks associated with starting treatment with Kisunla.

The study, however, did not detect any significant variations in another form of ARIA, namely cbrain bleeding, referred to as ARIA-H. The trial researchers contended that the study must enrol a substantially bigger cohort to identify a meaningful reduction in ARIA-H, as this phenomenon frequently occurs spontaneously, even in individuals not undergoing amyloid-targeting therapy.