A small tweak in the dosing regimen of Eli Lilly’s Alzheimer’s disease drug Kisunla has reduced brain swelling of patients in a trial, the company said Tuesday.
In the phase 3 study, 14% of patients who were on the altered dosing plan experienced brain swelling (ARIA-E) events at Week 24 versus 24% of those who received the standard dosing of Kisunla, which was approved by the FDA in July.
The difference adds up to a 41% reduction in ARIA-E and could lead to a label change and help convince doctors to prescribe the anti-amyloid therapy, which is competing with another Alzheimer’s drug in its class, Eisai and Biogen’s Leqembi.
The TRAILBLAZER-ALZ study is investigating the effect of different dosing regimens of Kisunla on the rates of ARIA-E and amyloid clearance in patients with early symptomatic Alzheimer’s. The results were presented Tuesday at the Clinical Trials on Alzheimer’s Disease conference in Madrid.
In the standard dosing regimen of Kisunla, patients receive 700 mg for their first three infusions, four weeks apart, followed by 1,400-mg doses at the same interval. The alternate dosing regimen that produced the statistically significant result is a more incremental plan as patients received 350 mg for their introductory dose, followed every four weeks by doses of 700 mg, 1050 mg and 1400 mg.
While 207 patients received standard dosing in the trial, 212 were given the modified regimen.
The study also examined those who have a genetic variant—apolipoprotein E (APOE4)—that makes them more likely to experience side effects from treatment with Kisunla. Of those individuals who were on a standard dose, there was a 57% incidence of ARIA-E, compared to a 19% incidence for those on the adjusted regimen. The difference translated to a 67% risk reduction with the altered dosing schedule.
Lilly is discussing the results of this study with global regulators, with the intent to submit for a potential label update for Kisunla.
“We are confident in the benefits of Kisunla’s currently approved dosing regimen and are excited that these results reveal a path to potentially improving on Kisunla’s profile by reducing the risk of ARIA-E,” Mark Mintun, M.D., Lilly’s group vice president for neuroscience R&D, said in a release.
As for the reductions in amyloid plaque, the two treatment arms had comparable results—67% for the modified group versus 69% for those on the standard regimen.
The study is ongoing with investigators planning to evaluate the potential reduction of ARIA-E after one year of treatment, Lilly said. The company expects to read out that follow-up early next year.
Last week, Eisai and Lilly came under fire for their conduct in clinical trials for their respective Alzheimer's drugs. Both companies genetically tested participants to identify those with a higher risk of developing the disease but didn’t disclose the results to patients—even though that genetic predisposition was also linked to a higher risk of brain injuries as a side effect of both drugs.