Mixed Results for Phase II Clinical Study of Atacicept in Lupus
The results of a phase II/III clinical study of atacicept for treatment of lupus did not show a statistically significant difference in the rate of flares between the group of individuals that received a weekly 75-milligram (mg) dose of the agent and those who received a placebo (58% vs. 54%), failing to meet the study’s primary endpoint (goal). There was statistical significance, however, in the flare rates among the 144 individuals that received a 150-mg dose (37 percent vs. 54 percent), but that arm of the study was suspended as a precaution after two trial participants who were receiving that dose died after developing infections.
The Lupus Foundation of America cautions that it is important not to over interpret data from Phase II trials since the explorations of the right and most optimal dose and optimal safety measures aren’t complete at that point. There is evidence from the data available that the 150-mg dose may be effective. However, careful evaluation for infection risk (or blood tests that warn of infection risk) will be very important to ensure patient safety in the continued development of this treatment. In that regard, we await the future results of the ongoing Phase III program.
Atacicept (TACI-Ig) was designed to block signals from a protein called immunoglobulin (Ig) that stimulates B cells. This is in the biologics class of drugs.
The study participants were randomized to receive either low or high doses of atacicept or placebo, plus their standard care. The study measured the number of lupus flares experienced by participants who completed 52 weeks of treatment. When the 150-mg arm of the study was halted, 62 patients had already completed the year's treatment and their results were analyzed separately. The organ systems that had the most prominent reduction in flares were the musculoskeletal and mucocutaneous (skin and mucous membrane) systems.
The study also measured time to flare (time between the start of treatment and the date that the participant experienced their first disease flare). Similar to the results seen for number of lupus flares, there was little difference in time to flare between the group receiving the 75-mg dose and placebo, with a longer time to flare seen among participants receiving the 150-mg dose.
There were some serological (blood-related) improvements seen in the trial. Immunoglobulin (IgG) levels fell by 30 percent among those receiving 75-mg of atacicept, and by 38 percent among those receiving 150-mg, compared with a 3 percent increase in IgG levels among participants receiving placebo. Anti-double stranded DNA antibodies decreased by 31 percent and 38 percent in the those who were treated with atacicept, but increased by 14 percent among individuals in the placebo group. Treatment with atacicept also demonstrated steroid-sparing qualities, allowing a reduction in the number of study participants who required steroids in excess of 20-mg per day.
Two phase III studies of atacicept among people with lupus are ongoing, and the Lupus Foundation of America will report those results when the studies conclude and the data has been analyzed.
The study was funded by EMD Serono, which is developing atacicept for use in treating autoimmune diseases. The results were reported online in the Annals of Rheumatic Diseases on June 20, 2014.