JNJ-63742057 (gosuranemab)

JNJ-63742057 (gosuranemab)

Overview

JNJ-63742057 (gosuranemab)

Overview

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">JNJ-63742057 (gosuranemab)</th>
</tr>
<tr>
<td class="label">Parameter</td>
<td>Details</td>
</tr>
<tr>
<td class="label">Phase</td>
<td>Phase I</td>
</tr>
<tr>
<td class="label">Population</td>
<td>Healthy volunteers, early AD</td>
</tr>
<tr>
<td class="label">Status</td>
<td>Completed</td>
</tr>
<tr>
<td class="label">Key Finding</td>
<td>Dose-dependent CSF tau reduction observed</td>
</tr>
<tr>
<td class="label">Parameter</td>
<td>Details</td>
</tr>
<tr>
<td class="label">NCT ID</td>
<td>NCT04619420</td>
</tr>
<tr>
<td class="label">Phase</td>
<td>Phase II</td>
</tr>
<tr>
<td class="label">Population</td>
<td>Early Alzheimer's disease (MCI-AD or mild AD)</td>
</tr>
<tr>
<td class="label">Status</td>
<td>Completed</td>
</tr>
<tr>
<td class="label">Primary Endpoint</td>
<td>Change in CSF biomarkers</td>
</tr>
<tr>
<td class="label">Secondary Endpoints</td>
<td>PET tau imaging, cognitive measures</td>
</tr>
<tr>
<td class="label">Antibody</td>
<td>Sponsor</td>
</tr>
<tr>
<td class="label">Gosuranemab (JNJ-63742057)</td>
<td>Janssen</td>
</tr>
<tr>
<td class="label">Semorinemab (RO7105685)</td>
<td>Roche</td>
</tr>
<tr>
<td class="label">Tilavonemab (ABBV-8E12)</td>
<td>AbbVie</td>
</tr>
<tr>
<td class="label">Bepranemab (UCB0107)</td>
<td>UCB</td>
</tr>
<tr>
<td class="label">E2814</td>
<td>Eisai</td>
</tr>
<tr>
<td class="label">Adverse Event</td>
<td>Frequency</td>
</tr>
<tr>
<td class="label">ARIA-E (amyloid-related imaging abnormality)</td>
<td>Uncommon</td>
</tr>
<tr>
<td class="label">Infusion reactions</td>
<td>Common</td>
</tr>
<tr>
<td class="label">Headache</td>
<td>Common</td>
</tr>
<tr>
<td class="label">Upper respiratory infection</td>
<td>Common</td>
</tr>
</table>

JNJ-63742057 (development code; generic name: gosuranemab) is a humanized anti-tau monoclonal antibody developed by [Johnson & Johnson](/companies/johnson-and-johnson) through its Janssen subsidiary for the treatment of Alzheimer's disease and other tauopathies["@alzforum"]. The antibody targets extracellular tau oligomers and aggregates, with the goal of preventing the spread of pathological tau throughout the brain. Gosuranemab represents one of several anti-tau antibody programs that have advanced to clinical testing, though the field has faced significant challenges with efficacy["@mullard2022"].

Mechanism of Action

Target

JNJ-63742057 is designed to bind to aggregated tau species[@chen2023]:

• Primary Target: Tau oligomers and aggregates
• Epitope: Mid-domain region of tau protein
• Binding Specificity: Prefers pathologically aggregated tau over monomeric tau
• Goal: Neutralize extracellular tau species that mediate prion-like spread

Mechanism

The antibody operates through several mechanisms[@tian2024]:

The rationale for targeting extracellular tau comes from the observation that pathological tau spreads along neuroanatomical pathways in a pattern consistent with trans-synaptic transmission. By intercepting tau species in the extracellular space, gosuranemab may prevent the progression of tau pathology to previously unaffected brain regions.

Clinical Development

Phase I Trial (NCT02874989)

First-in-human studies evaluated the safety, tolerability, and pharmacokinetics of JNJ-63742057 in healthy volunteers and patients with early Alzheimer's disease[@alzforum]:

The Phase I trial established the safety profile and identified doses that achieved meaningful target engagement in cerebrospinal fluid.

Phase II Trial (NCT04619420)

A Phase II clinical trial evaluated JNJ-63742057 in patients with early Alzheimer's disease[@nct04619420][@tian2024]:

The trial utilized phosphorylated tau biomarkers (particularly p-tau217) as both a patient selection criterion and outcome measure, reflecting the growing importance of tau biomarkers in AD clinical trials.

Results and Outcomes

The Phase II trial results showed[@tian2024]:

• Biomarker Effects: Dose-dependent reduction in CSF p-tau217 levels
• Target Engagement: Evidence of antibody binding to tau in CSF
• Cognitive Outcomes: No significant difference on primary cognitive endpoints
• Safety Profile: Generally consistent with other anti-tau antibodies

Comparison to Other Anti-Tau Antibodies

Rationale for Tau Immunotherapy

Tau Pathology in Alzheimer's Disease

Tau protein aggregation is a hallmark of Alzheimer's disease neuropathology:

• Neurofibrillary tangles: Paired helical filaments of hyperphosphorylated tau
• Progression pattern:Braak staging correlates with clinical severity
• Tau spread: Temporal progression follows connected neural networks
• Clinical correlation: Tau burden correlates with cognitive decline better than amyloid

Challenges in Tau-Targeted Therapy

The field has faced significant challenges[@mullard2022]:

Safety and tolerability

The safety profile of JNJ-63742057 has been characterized across multiple studies:

The incidence of ARIA was notably lower than observed with anti-amyloid antibodies, potentially reflecting the lack of significant interaction with vascular amyloid.

Current Status and Future Directions

JNJ-63742057 (gosuranemab) remains in clinical development as part of Janssen's neuroscience portfolio. The program continues to evaluate:

• Combination approaches: Potential synergy with anti-amyloid antibodies
• Biomarker stratification: Identifying patients most likely to benefit
• Earlier intervention: Testing in preclinical or prodromal AD
• Alternative delivery: Intrathecal or enhanced peripheral delivery

See Also

• [Tau Immunotherapy](/therapeutics/tau-immunotherapy)
• [Tau Protein](/proteins/tau)
• [Alzheimer's Disease Therapeutics](/therapeutics/alzheimers-disease-therapeutics)
• [Anti-Tau Therapeutics](/therapeutics/anti-tau-therapeutics)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving JNJ-63742057 (gosuranemab) discovered through SciDEX knowledge graph analysis: