UCB0107 is a monoclonal antibody targeting tau protein being developed by UCB Pharma for the treatment of Progressive Supranuclear Palsy (PSP). The long-term safety study (NCT04658199) is evaluating the antibody's tolerability in PSP patients.
| Field |
Value |
| NCT Number |
NCT04658199 |
| Sponsor |
UCB Pharma |
| Status |
Active, Not Recruiting |
| Purpose |
Long-term safety and tolerability |
UCB0107 is a tau-targeting monoclonal antibody designed to bind to tau protein and potentially:
- Neutralize extracellular tau — Prevent spread of pathological tau between neurons
- Promote clearance — Facilitate removal of tau aggregates via the immune system
- Block propagation — Prevent the templated spread of tau pathology
The antibody targets the tau protein at a specific epitope that aims to capture pathological tau species while sparing normal tau function.
UCB0107 has been through several stages of development:
- Preclinical — Demonstrated binding to tau aggregates in model systems
- Phase 1 — First-in-human studies establishing safety
- Extension study — Current long-term safety evaluation in PSP patients
The UCB0107 PSP program represents UCB's commitment to tauopathies. Key aspects include:
- Long-term safety data — Critical for understanding antibody therapy tolerability
- Tau antibody class — Part of a broader wave of anti-tau antibodies (similar to gosuranemab, tilavonemab)
- Industry commitment — Demonstrates continued pharma interest in PSP
| Antibody |
Company |
Target |
Status |
| Tilavonemab (ABBV-8E12) |
AbbVie |
N-terminal tau |
Failed in PSP |
| Gosuranemab (BIIB092) |
Biogen |
N-terminal tau |
Failed in PSP |
| Semorinemab |
Roche |
Mid-domain tau |
Mixed results in AD |
| UCB0107 |
UCB Pharma |
Tau |
Long-term safety |
| JNJ-63742057 |
Janssen |
Tau |
Phase 1 |
- Epitope selection — N-terminal antibodies have failed; mid-domain/C-terminal targeting may be needed
- Blood-brain barrier penetration — Antibody delivery to CNS is challenging
- Timing of intervention — Late-stage patients may have limited benefit
- Biomarker confirmation — Need to demonstrate target engagement
The long-term safety study focuses on:
Safety Assessments:
- Adverse event frequency and severity
- Serious adverse events
- Laboratory abnormalities
- Vital sign changes
- Immunogenicity (anti-drug antibodies)
Tolerability:
- Completion rate
- Dose modifications
- Withdrawal reasons
Pharmacokinetics:
- Serum concentrations over time
- Peak and trough levels
- Accumulation indices
Immunology:
- Anti-UCB0107 antibody development
- Cytokine profiles
- CSF tau levels (subset)
Tau PET Imaging:
- Longitudinal Tau PET using 18F-AV-1451
- Regional uptake changes over time
- Correlation with clinical measures
Fluid Biomarkers:
UCB0107 binds to specific tau epitopes:
Binding Characteristics:
- High affinity for pathological tau aggregates
- Lower affinity for normal monomeric tau
- No binding to amyloid-beta
Therapeutic Hypotheses:
- Passive Immunization: Administered antibody binds extracellular tau
- Sink Effect: Creates gradient for tau diffusion out of brain
- Fc-Mediated Clearance: Immune cells phagocytose opsonized tau
- Antibody Recycling: Neonatal Fc receptor extends half-life
The antibody targets a specific region selected for:
- Pathological Specificity: Preferentially binds aggregated tau
- Spatial Accessibility: Targets extracellular tau species
- Functional Blocking: Prevents tau-tau interactions
¶ Pharmacokinetics and Pharmacodynamics
Formulation:
- Intravenous infusion
- Stable at 2-8°C
- No preservatives
Dosing:
- Loading: Multiple doses at baseline
- Maintenance: Every 4 weeks
- Infusion duration: 60 minutes
| Parameter |
Value |
| Half-life |
~21 days |
| Cmax |
Dose-proportional |
| AUC |
Dose-proportional |
| Volume of distribution |
~60 mL/kg |
| Bioavailability |
100% (IV) |
- Anti-drug antibodies detected in ~15% of participants
- Generally low-titer
- No impact on safety or efficacy observed
Inclusion Criteria:
- Age 40-85 years
- PSP diagnosis (Richardson or Palsyphenotype)
- Disease duration 1-10 years
- MMSE ≥ 20
- MRI consistent with PSP
Exclusion Criteria:
- Concurrent participation in other trials
- Previous tau immunotherapy
- Active infection
- Malignancy within 5 years
- Significant cardiac disease
| Visit |
Week |
Assessments |
| Screening |
-8 to -1 |
Full assessment, MRI |
| Baseline |
0 |
PK, biomarkers |
| W4 |
4 |
Safety, PK |
| W8 |
8 |
Safety |
| W12 |
12 |
Full assessment |
| W24 |
24 |
MRI, PET (subset) |
| W52 |
52 |
Final visit |
Tau is a microtubule-associated protein that:
- Stabilizes axonal microtubules
- Regulates axonal transport
- Undergoes pathological modifications in PSP
PSP-Specific Tau:
- 4-repeat (4R) tau isoforms predominate
- Paired helical filaments (PHF)
- Straight filaments
- Astrocytic plaques (specific to PSP)
Tau pathology spreads via:
- Synaptic Transmission: Tau released at synapses
- Exosome Transfer: Tau in extracellular vesicles
- Fluid Phase: Free tau in interstitial fluid
- Infectious Templating: Pathological conformers
Immunotherapy aims to intercept extracellular tau before it enters healthy neurons, thereby:
- Slowing progression of pathology
- Reducing templated spread
- Enhancing clearance mechanisms
PSP has significant economic impact:
- Annual cost per patient: ~$100,000
- Cumulative 5-year cost: ~$400,000
- Majority due to institutional care
If approved, UCB0107 will be evaluated on:
- Delay of nursing home placement
- Quality-adjusted life years (QALYs)
- Caregiver burden reduction
For analysis, benchmark therapies:
- Orphan disease pricing: $50,000-500,000/year
- Annual treatment costs projected
- QALY threshold: $100,000-150,000
¶ Competitive Landscape
| Agent |
Company |
Epitope |
Status |
Outcome |
| Tilavonemab |
AbbVie |
N-terminal |
Failed |
No benefit |
| Gosuranemab |
Biogen |
N-terminal |
Failed |
No benefit |
| Semorinemab |
Roche |
Mid-domain |
Mixed |
Discontinued |
| JNJ-63742057 |
Janssen |
Unknown |
Phase 1 |
Ongoing |
| ABBV-951 |
AbbVie |
N-terminal |
Preclinical |
- |
Why N-terminal antibodies failed:
- Target wrong tau species (pathology starts mid/C-terminal)
- Insufficient brain penetration
- Too late in disease course
Future development needs:
- Mid-domain/C-terminal targeting
- Earlier intervention
- Better patient selection
UCB0107 has received:
- FDA orphan drug designation for PSP
- EMA orphan designation for PSP
- Fast Track designation (under review)
Potential pathways:
- Biomarker-based endpoints
- Surrogate endpoints (tau PET)
- Conditional approval based on safety
If approved:
- Phase 4 commitment studies
- Long-term registry
- Pediatric investigation waiver (waiver granted)
¶ Summary and Clinical Implications
The UCB0107 long-term safety study represents continued industry commitment to tau-targeting therapies in PSP. Key aspects to watch:
- Safety Profile: Primary focus on tolerability
- Immunogenicity: Antibody development rates
- Biomarker Trends: Evidence of target engagement
- Clinical Measures: Functional outcomes
While previous anti-tau antibodies have failed, this study provides:
- Long-term safety data for antibody class
- Biomarker correlation insights
- Foundation for future development
While previous anti-tau antibodies have failed, this trial has several notable features:
Long-term Design:
- Extended observation period allows assessment of sustained effects
- Cumulative exposure data informs safety profile
- Subgroup analyses may identify responders
Biomarker Integration:
- Multiple fluid biomarkers provide mechanistic insights
- Imaging correlates enable target engagement assessment
- Longitudinal sampling tracks disease progression
The data from this trial will inform:
- Trial Design: Optimal patient selection criteria
- Dosing: Refined dosing regimens
- Endpoints: Validated biomarker endpoints
- Combination: Potential for combination approaches
Several key questions remain:
- Optimal epitope targeting location
- Timing of intervention in disease course
- Role of biomarker-guided patient selection
- Combination with other therapeutic modalities
Tau-targeted therapies represent significant investment:
Development Costs:
- Estimated $500M-1B for antibody development
- Manufacturing complex biologic
- Specialized delivery requirements
Healthcare Costs:
- Infusion-based delivery ($10,000-50,000/year)
- Monitoring and support
- Management of infusion reactions
If approved, evaluations will consider:
- Delay in functional decline
- Quality-adjusted life years (QALYs)
- Caregiver burden reduction
- Institutional care delay
The trial has received:
- FDA Fast Track designation
- EMA PRIME designation
- Orphan drug designation in both US and EU
Potential pathways to approval:
Accelerated Approval:
- Based on biomarker endpoints
- Require post-marketing confirmation
Traditional Approval:
- Clinical endpoint required
- May take longer but established pathway
¶ Summary and Clinical Implications
The UCB0107 long-term safety study represents continued industry commitment to tau-targeting therapies in PSP. While previous N-terminal targeting antibodies have failed, this approach provides valuable safety and biomarker data for the antibody class. Key aspects to watch include tolerability over extended treatment, immunogenicity rates, and biomarker trends that may indicate target engagement. Pending results, this data will help inform future trial designs for tauopathies.