Vivoryon Therapeutics N.V. Shares Clinical Development Update Highlighting Progress of N3pE-Amyloid-targeting Small Molecule Varoglutamstat in Alzheimer’s Disease - Seite 3

Varoglutamstat is designed to prevent N3pE- Abeta formation, rather than aiming to clear existing plaques, making it an intervention upstream of other approaches such as monoclonal antibodies (mAbs). Through a second mode of action, varoglutamstat also modulates neuroinflammation via the CCL2 pathway, which, in turn, has an impact on tau pathology.

Varoglutamstat was shown to be well-tolerated in both a completed first-in-human Phase 1 study in over 200 participants and the subsequent first-in-patient Phase 2a study, SAPHIR (NCT02389413), which enrolled 120 patients suffering from early AD. Importantly, after only 12 weeks of treatment, this study showed evidence of improving not only pathological hallmarks, but also synaptic function and connectivity, cognition, memory and attention in AD patients, including statistically significant changes from baseline in working memory.

VIVIAD (NCT04498650) is a state-of-the-art Phase 2b study being conducted in Europe and designed to evaluate the safety, tolerability, and efficacy of varoglutamstat in 259 (final number of randomized participants) subjects with mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD).

• Data from AAIC 2023: P1-18 / P1-904 Poster #82642 – “VIVIAD, a Phase 2b Study Investigating Varoglutamstat in Patients with MCI or Mild AD: Analysis of Baseline Cognition Data.” These data demonstrate that Vivoryon’s strategy of recruiting individuals with evidence of baseline deficits on the WAIS-IV Coding test, a well-known measure of cognitive function, successfully enriches study cohorts with respect to deficits in attention and working memory, enabling reliable assessment of potential cognitive improvement after treatment.
  • A new enrichment strategy was applied in the VIVIAD study to ensure that study participants exhibited rescuable deficits in attention and working memory at baseline. VIVIAD uses the WAIS-IV Coding test to select patients with rescuable cognitive deficits in the target domains. The study inclusion criteria encompassed a score of at least 0.5 SD (standard deviations) below age-adjusted mean on the WAIS-IV Coding subtest.
  • Approximately 20% of screened patients did not meet the inclusion criteria during screening due to good performance on the WAIS-IV Coding test. In addition, for selecting patients with mild disease, the MMSE cut-off was set at 20, leading to 8% of patients not meeting the inclusion criteria due to falling under this cut-off value.
  • The WAIS-IV Coding test performance shows reasonably good correlation with the measures that comprise the primary outcome, i.e. detection (DET), identification (IDN) and one back test (ONB) of the Cogstate NTB as judged by the Spearman correlation coefficients of 0.27, 0.44, and 0.47, respectively, using the blinded baseline data of all randomized patients.

• The use of MMSE and WAIS-IV Coding test, together with inclusion criteria based on CSF biomarkers (Abeta and p-tau) are valuable tools in identifying and recruiting patients with MCI or mild AD who already have deficits in working memory and attention.