Eledon Announces Positive Topline Results from Phase 2a Trial of Tegoprubart Demonstrating Safety, Target Engagement, and Biomarker Response in Patients Living with Amyotrophic Lateral Sclerosis
- Tegoprubart was well-tolerated, with no drug-related serious adverse events
- Dose dependent target engagement was demonstrated, and ALS associated pro-inflammatory biomarkers were both observed and significantly reduced in a dose dependent manner
- Target engagement and level of pro-inflammatory biomarker reduction were associated with a trend in the slowing of disease progression as measured by ALSFRS slope when compared to a cohort from the ALS PRO-ACT database
- Biomarkers significantly reduced included biomarkers also associated with IgA nephropathy and kidney allograft transplant rejection
- Eledon management will host a webcast and conference call regarding these clinical results at
8:00 a.m. ETtoday, May 31, 2022
Tegoprubart is an investigational humanized monoclonal antibody that inhibits CD40 Ligand (CD40L), a membrane protein linked to increased peripheral immune responses and neuroinflammation in ALS. The 12-week trial included 54 patients with ALS at 13 treatment sites in
Tegoprubart successfully met the primary endpoints of safety and tolerability. Adverse events were equally distributed across dose levels. Tegoprubart was well-tolerated, and no drug-related serious adverse events were observed. Anti-drug antibodies (ADAs) were present in less than 5 percent of samples. All ADAs were of low titer and did not impact tegoprubart drug levels.
Tegoprubart target engagement was demonstrated at the 4 and 8 mg / kg dosing levels using CD40L and CXCL13 biomarkers related to T cell and B cell function, respectively. A pro-inflammatory ALS signature was identified, consisting of 32 different inflammatory biomarkers in the tested population, including TNF-α, MCP1, EN-RAGE, C-Reactive Protein (CRP), and IL-6. IL-1 was not significantly detected in the study patient population. Dose dependent, significant reductions were observed in up to 23 of these biomarkers, including TNF-α, MCP1, EN-RAGE, and CRP. Other pro-inflammatory biomarkers significantly reduced included biomarkers also associated with IgA nephropathy and kidney transplant rejection, such as IgA, IgE, IgM, C3, CXCL9, and CXCL10. While the study was neither primarily designed nor powered to assess the effect of tegoprubart on ALS Functional Rating Scale (“ALSFRS”), both target engagement and level of pro-inflammatory biomarker reduction were associated with a trend in the slowing of disease progression as measured by ALSFRS slope when compared to a cohort from the ALS PRO-ACT database2.
“Neuroinflammation is a driving force in the pathogenesis and progression of ALS. The ability to suppress inflammatory responses may translate into clinical benefit,” said
“These positive Phase 2a topline trial results demonstrated target engagement and a reduction in key inflammatory biomarkers in patients living with ALS,” said
“There would be no tegoprubart without the resolve of so many ALS patients and their families who supported the early drug discovery efforts for tegoprubart, and who continue to champion the scientific advancement of ALS research,” said
Conference Call and Webcast Details
Eledon management will host a webcast and conference call regarding these clinical results at
ALS, commonly known as
About the Phase 2a Study of Tegoprubart
This Phase 2a, multi-center, open label, multiple dose study of tegoprubart enrolled 54 adults with ALS at treatment sites in
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1 ClinicalTrials.gov Identifier: NCT04322149. https://clinicaltrials.gov/ct2/show/NCT04322149?term=at-1501&draw=2&rank=4
2 PRO-ACT (Pooled Resource Open-access ALS Clinical Trials) Database
3 10 Facts About ALS. https://www.research.va.gov/programs/tissue_banking/als_caregivers/ALSFactSheet_NAR.pdf
Source: Eledon Pharmaceuticals, Inc.