UB-311 vaccine found safe, slows decline in mild Alzheimer’s: Trial
93% of patients in study had an antibody response against beta-amyloid
Vaccine candidate UB-311 is safe, well tolerated, and triggered an antibody response against beta-amyloid in 93% of patients with mild Alzheimer’s disease, according to now published data from a Phase 2a trial.
Immunization also led to nonsignificant trends in reducing beta-amyloid and slowing cognitive, functional, and dementia decline, data indicated.
“This publication supports the innovative work that we and our collaborators are conducting to advance UB-311 for the potential treatment, and even prevention, of Alzheimer’s disease,” Mei Mei Hu, CEO of Vaxxinity (formerly United Neuroscience), the therapy’s developer, said in a company press release.
“Imagine expanding the addressable patient population of beta-amyloid immunotherapies by multiple orders of magnitude, potentially over 1,000x, and delivering life-changing medicine at a fraction of the cost,” Hu added. “That is our vision for UB-311 and the potential power of active immunotherapies.”
Details of the trial were published in the journal eBioMedicine, in the study, “Safety, tolerability, immunogenicity, and efficacy of UB-311 in participants with mild Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase 2a study.”
Clearing beta-amyloid prevents nerve damage, slows dementia
UB-311 is a lab-made vaccine designed to trigger an immune response against beta-amyloid — a protein that misfolds and forms toxic clumps in the brain in people with Alzheimer’s, causing nerve cell damage. Its goal is the sustained clearance of beta-amyloid to prevent nerve damage and slow or halt symptoms of dementia.
“Vaccine approaches such as UB-311 represent important ways forward in advancing treatment and prevention of Alzheimer’s disease and offer the potential to transform the treatment landscape by providing participants with an accessible therapeutic option,” said Jeffrey Cummings, MD, PhD, the study’s co-author and director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas.
A previous Phase 1 trial (NCT00965588) demonstrated UB-311’s safety and tolerability in patients with mild to moderate Alzheimer’s. The vaccine also generated high levels of anti-beta-amyloid antibodies and potentially stabilized cognitive abilities.
Conducted at multiple sites in Taiwan, the Phase 2a study (NCT02551809) enrolled 43 patients, ages 60-90 years, diagnosed with mild Alzheimer’s disease. Most participants (81%) carried the APOE-E4 genetic factor associated with a higher risk of developing early Alzheimer’s.
Over 60 weeks, 14 participants were randomly assigned to receive seven intramuscular injections of UB-311 (group Q3M), 15 received five doses of UB-311 and two doses of placebo (group Q6M), and 14 others were given a placebo.
The study’s primary goals were the safety and tolerability of the vaccine, and its ability to elicit an antibody response compared with a placebo after 78 weeks (18 months). Secondary objectives included changes in cognitive and neuropsychiatric function, as well as the impact on learning and memory.
MRI scans were performed at the study’s start and every three months post-vaccination to assess amyloid-related imaging abnormalities (ARIA), a group of side effects associated with anti-amyloid therapies, including brain bleeds (ARIA-H) and brain swelling (ARIA-E).
Meeting its primary goal, UB-311 was found to be safe and well tolerated. A total of 43 treatment-emergent adverse events (TEAEs), reported by 19 participants, were considered drug-related by the trial investigator. No TEAEs were seen in lab data, physical examinations, vital signs, or heart tests.
TEAEs with the highest incidence included injection-site pain (16%) and diarrhea (12%). HRIA-H accounted for 12 TEAEs experienced by six (14%) participants.
A total of 11 new (from the previous visit) ARIA-H events occurred, with four in the Q3M arm, four in the Q6M arm, and three with placebo. Eight of these 11 (73%) new cases with small brain bleeds were APOE4 carriers. No large brain bleeds, or ARIA-E were observed.
93% of patients had an antibody response to UB-311 vaccine candidate
By the end of the study, 12 of the 14 patients (86%) who received the Q3M regimen had an antibody response, as did all 15 of those in the Q6M arm, with a combined response rate of 93%. Differences between vaccine regimens were not statically significant.
“The UB-311 Phase 2a program accomplished its goals of establishing safety and tolerability, while generating high levels of anti-amyloid antibodies,” Cummings said. “The gradual, natural [increase] of antibody [levels] through this approach may have contributed to a lack of ARIA-E in this study.”
On average, all participants experienced a reduction in cognitive, functional, and global measures over the 78-week period. Those who received the vaccine, however, showed a slower decline in these secondary outcomes compared with the placebo group, and the data favored the more frequent dosing Q3M arm (seven doses), although no statistically significant differences in treatments were observed.
Data from positron emission tomography (PET) scans using a radioactive molecule (florbetapir) that binds to beta-amyloid showed nonsignificant trends at week 52 toward reduced beta-amyloid in the UB-311 treatment groups. Trends for lower amyloid burden by week 78 were observed only in the Q3M regimen group. In comparison, the placebo group showed a slight nonsignificant increase in amyloid load.
Taken together, the results showed that “UB-311 was safe, well-tolerated, and generated a robust immune response,” the researchers wrote. “Although not powered for efficacy analyses, clinical outcomes [of this study] were promising and will help determine optimal sample sizes for future clinical trials.
“The successful completion of this phase 2a study represents an important milestone in the advancement of this treatment modality with important public health implications and supports the continued development of UB-311 for treatment of Alzheimer’s disease.”
The study was funded by Vaxxinity, and three of the 12 study authors were affiliated with the company.