- Results provide first evidence of biological and clinical effect of a mid-domain tau-targeting disease-modifying therapy1
- In full study population primary endpoint was not met, however in key secondary endpoints bepranemab slowed cognitive decline and rate of tau accumulation2
- In pre-defined patient subgroups, consistent treatment benefit shown across multiple primary and secondary outcome measures, including cognition and function2
- UCB is evaluating next steps in the development program
BRUSSELS, Belgium I October 31, 2024 I UCB today reported Phase 2a data from the TOGETHER (AH0003) study, investigating the safety, efficacy, and tolerability of bepranemab – an investigational anti-tau antibody targeting the mid-region of the tau protein – in people living with prodromal to mild Alzheimer’s disease3. The results were presented during a late-breaking symposium at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) meeting (Madrid, Spain, October 29 – November 1, 2024).
“We are deeply encouraged by the proof-of-concept data for bepranemab, which highlight its potential to impact early Alzheimer’s disease progression. This strengthens our belief in the value of targeting the mid-region of tau as an important strategy in altering the trajectory of the disease,” said Alistair Henry, Chief Scientific Officer at UCB. “We extend heartfelt thanks to the patients, families and friends, and dedicated clinical trial teams who have partnered with us on this important research. Their support is invaluable as we continue to explore the next steps in bepranemab’s development.”
Full study population2
In the overall study population, no beneficial effect of low- or high-dose bepranemab compared with placebo was observed on the primary endpoint, Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score at Week 80 (CDR-SB is a measure of cognition and function). However, at Week 80, in key secondary endpoints, treatment with bepranemab (45mg/kg and 90mg/kg):
- Slowed the rate of tau accumulation versus placebo in key brain regions by 33%-58%.
- Slowed cognitive decline by 21-25% versus placebo – the change between Baseline and Week 80 in the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) total score.
Consistent treatment effect in sub-group analysis2
In two predefined subgroups, low tau burden at Baseline and APOε4* non-carriers, treatment benefits were observed across multiple outcome measures. In a post-hoc subgroup analysis comprising participants with low tau at Baseline or those who are APOε4 non-carriers (approximately 50% of the full study population), high-dose bepranemab (90mg/kg):
- Slowed the rate of tau accumulation versus placebo in key brain regions by 63%-67% at Week 80.
- Slowed clinical disease progression by 29% – as measured by the change in CDR-SB between Baseline and Week 80.
- Slowed disease progression according to secondary/exploratory endpoints, including measures of Activities of Daily Living by 41-54% at Week 80.
In the subgroup comprising participants with high tau at Baseline who were also APOε4 carriers, treatment with high-dose bepranemab showed no benefit across almost all clinical endpoints with effects on CDR-SB, A-iADL-Q and ADCS-ADL scores favoring the placebo arm.
Safety data2
Bepranemab had an acceptable safety profile and was generally well tolerated. Brain haemorrhagic and inflammatory changes were similar between placebo and bepranemab treatment arms. Incidence of Treatment Emergent Adverse Events (TEAEs), drug-related TEAEs, and TEAEs leading to dropout were comparable between the treatment arms. Most reported TEAEs were infections and infestations (placebo 50.3% / bepranemab 50.2%), nervous system disorders (placebo 40.1% / bepranemab 35.2%) and musculoskeletal disorders (placebo 26.8% / bepranemab 28.3%).
About TOGETHER study3
TOGETHER is a Phase 2a double-blind, placebo-controlled, three-arm study, randomizing patients to placebo, low, or high dose bepranemab. A total of 466 patients participated in the study and were treated in the double-blind phase for 80 weeks. The majority of participants have now entered the 48-week open-label extension (OLE) period with planned bepranemab treatment for 44 weeks, followed by a safety follow-up visit 20 weeks after the last infusion.
About bepranemab
Bepranemab is a monoclonal antibody (mAb) that specifically targets a mid-region epitope of human tau4,5. In pathological conditions, the mid-region of tau is thought to be essential for tau aggregation and is a key driver of neurodegeneration in Alzheimer’s disease6.
*APOε4 is the primary genetic risk factor for sporadic Alzheimer’s disease.
This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval.
About UCB
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 9,000 people in approximately 40 countries, the company generated revenue of €5.3 billion in 2023. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news.
References:
- Imbimbo B, et al. Initial failures of anti-tau antibodies in Alzheimer’s disease are reminiscent of the amyloid-β story. Neural Regeneration Research. 2023; 18(1): 117-118.
- Barton M, et al. Results from TOGETHER, a double-blind, placebo-controlled Phase II study evaluating efficacy, safety and tolerability of bepranemab in prodromal–mild AD. Presented at: 17th Clinical Trials on Alzheimer’s Disease (CTAD), Madrid (Spain) October 29 – November 1, 2024.
- https://www.ucb.com/clinical-studies/Clinical-Trials?studyId=AH0003. Accessed October 2024.
- Albert M, et al. Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody. Brain. 2019;142(6):1736–1750.
- Courade JP, et al. Epitope determines efficacy of therapeutic anti-Tau antibodies in a functional assay with human Alzheimer Tau. Acta Neuropathol. 2018;136(5):729–745.
- Roberts M, et al. Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer’s disease. Acta Neuropathol Commun. 2020;8(1):13.
SOURCE: UCB
Post Views: 208
- Results provide first evidence of biological and clinical effect of a mid-domain tau-targeting disease-modifying therapy1
- In full study population primary endpoint was not met, however in key secondary endpoints bepranemab slowed cognitive decline and rate of tau accumulation2
- In pre-defined patient subgroups, consistent treatment benefit shown across multiple primary and secondary outcome measures, including cognition and function2
- UCB is evaluating next steps in the development program
BRUSSELS, Belgium I October 31, 2024 I UCB today reported Phase 2a data from the TOGETHER (AH0003) study, investigating the safety, efficacy, and tolerability of bepranemab – an investigational anti-tau antibody targeting the mid-region of the tau protein – in people living with prodromal to mild Alzheimer’s disease3. The results were presented during a late-breaking symposium at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) meeting (Madrid, Spain, October 29 – November 1, 2024).
“We are deeply encouraged by the proof-of-concept data for bepranemab, which highlight its potential to impact early Alzheimer’s disease progression. This strengthens our belief in the value of targeting the mid-region of tau as an important strategy in altering the trajectory of the disease,” said Alistair Henry, Chief Scientific Officer at UCB. “We extend heartfelt thanks to the patients, families and friends, and dedicated clinical trial teams who have partnered with us on this important research. Their support is invaluable as we continue to explore the next steps in bepranemab’s development.”
Full study population2
In the overall study population, no beneficial effect of low- or high-dose bepranemab compared with placebo was observed on the primary endpoint, Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score at Week 80 (CDR-SB is a measure of cognition and function). However, at Week 80, in key secondary endpoints, treatment with bepranemab (45mg/kg and 90mg/kg):
- Slowed the rate of tau accumulation versus placebo in key brain regions by 33%-58%.
- Slowed cognitive decline by 21-25% versus placebo – the change between Baseline and Week 80 in the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) total score.
Consistent treatment effect in sub-group analysis2
In two predefined subgroups, low tau burden at Baseline and APOε4* non-carriers, treatment benefits were observed across multiple outcome measures. In a post-hoc subgroup analysis comprising participants with low tau at Baseline or those who are APOε4 non-carriers (approximately 50% of the full study population), high-dose bepranemab (90mg/kg):
- Slowed the rate of tau accumulation versus placebo in key brain regions by 63%-67% at Week 80.
- Slowed clinical disease progression by 29% – as measured by the change in CDR-SB between Baseline and Week 80.
- Slowed disease progression according to secondary/exploratory endpoints, including measures of Activities of Daily Living by 41-54% at Week 80.
In the subgroup comprising participants with high tau at Baseline who were also APOε4 carriers, treatment with high-dose bepranemab showed no benefit across almost all clinical endpoints with effects on CDR-SB, A-iADL-Q and ADCS-ADL scores favoring the placebo arm.
Safety data2
Bepranemab had an acceptable safety profile and was generally well tolerated. Brain haemorrhagic and inflammatory changes were similar between placebo and bepranemab treatment arms. Incidence of Treatment Emergent Adverse Events (TEAEs), drug-related TEAEs, and TEAEs leading to dropout were comparable between the treatment arms. Most reported TEAEs were infections and infestations (placebo 50.3% / bepranemab 50.2%), nervous system disorders (placebo 40.1% / bepranemab 35.2%) and musculoskeletal disorders (placebo 26.8% / bepranemab 28.3%).
About TOGETHER study3
TOGETHER is a Phase 2a double-blind, placebo-controlled, three-arm study, randomizing patients to placebo, low, or high dose bepranemab. A total of 466 patients participated in the study and were treated in the double-blind phase for 80 weeks. The majority of participants have now entered the 48-week open-label extension (OLE) period with planned bepranemab treatment for 44 weeks, followed by a safety follow-up visit 20 weeks after the last infusion.
About bepranemab
Bepranemab is a monoclonal antibody (mAb) that specifically targets a mid-region epitope of human tau4,5. In pathological conditions, the mid-region of tau is thought to be essential for tau aggregation and is a key driver of neurodegeneration in Alzheimer’s disease6.
*APOε4 is the primary genetic risk factor for sporadic Alzheimer’s disease.
This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval.
About UCB
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 9,000 people in approximately 40 countries, the company generated revenue of €5.3 billion in 2023. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news.
References:
- Imbimbo B, et al. Initial failures of anti-tau antibodies in Alzheimer’s disease are reminiscent of the amyloid-β story. Neural Regeneration Research. 2023; 18(1): 117-118.
- Barton M, et al. Results from TOGETHER, a double-blind, placebo-controlled Phase II study evaluating efficacy, safety and tolerability of bepranemab in prodromal–mild AD. Presented at: 17th Clinical Trials on Alzheimer’s Disease (CTAD), Madrid (Spain) October 29 – November 1, 2024.
- https://www.ucb.com/clinical-studies/Clinical-Trials?studyId=AH0003. Accessed October 2024.
- Albert M, et al. Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody. Brain. 2019;142(6):1736–1750.
- Courade JP, et al. Epitope determines efficacy of therapeutic anti-Tau antibodies in a functional assay with human Alzheimer Tau. Acta Neuropathol. 2018;136(5):729–745.
- Roberts M, et al. Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer’s disease. Acta Neuropathol Commun. 2020;8(1):13.
SOURCE: UCB
Post Views: 208
