Spinogenix’s lead candidate, tazbentetol, has shown early signs of sustained, cumulative cognitive benefits in patients with mild-to-moderate Alzheimer’s disease in a mid-stage study.
During a Phase IIa trial (NCT06427668), the once-daily oral small molecule showed early cognitive benefit, with patients receiving the high (300mg) dose experiencing a >2.5-point average increase in standardised mini-mental state examination (SMMSE) scores versus placebo within four weeks of treatment.
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This effect on SMMSE was sustained across patients who continued treatment in a 24-week open-label extension (OLE) period. A similar impact was seen in other key primary endpoint measures, including clinical dementia rating sum of boxes (CDR-SB) and activities of daily living (ADL) values.
After the 24-week period, patients were given the option to stay on treatment for an additional 52 weeks. During this time,
tazbentetol demonstrated increasing benefits, with both ADL and CDR-SB scores seeing improvements over baseline measures after 40 weeks of treatment.
Tazbentetol also exhibited impacts on neurophysiological biomarkers of synaptic regeneration, as patients experienced a reversal of cortical “slowing”, according to measures of brain activity recorded through electroencephalogram (EEG) scans.
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By GlobalDataOnce-daily treatment with tazbentetol – formerly known as SPG302 – was also proven to be tolerable and safe. No severe treatment-emergent adverse events (TEAEs) were observed when tazbentetol was used as a monotherapy or in combination with standard of care (SoC) cholinesterase inhibitors.
These topline results were originally presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference on 4 December.
Next steps for tazbentetol
Following the promising results of the Phase IIa trial in Alzheimer’s, Spinogenix is looking to explore tazbentetol’s potential in the indication further through a late-stage trial.
The US Food and Drug Administration (FDA) has already accepted an investigational new drug (IND) application for tazbentetol in Alzheimer’s disease, which will facilitate the initiation of a “registrational or registrational-directed study”.
Moving forward, Spinogenix’s CCO Sharron Gargosky noted that the biotech will communicate further with the FDA, which will guide the next steps for the drug in Alzheimer’s disease.
While the Phase IIa study revolved around patients with mild-to-moderate disease, Gargosky said that Spinogenix is also looking to explore the drug’s potential in both the preventive and late-stage settings in conversation with Clinical Trials Arena.
If approved, tazbentetol could become the first regenerative drug to obtain FDA approval for Alzheimer’s disease. It would enter a market that GlobalData estimates will be worth $19.3bn by 2033.
Outside of Alzheimer’s, Spinogenix also posted a win for tazbentetol in amyotrophic lateral sclerosis (ALS), which will see the therapy advance to a registrational trial after it triggered a stable or improved rate of ALS-associated decline in 82% of patients during a mid-stage study.
The company is also exploring tazbentetol’s efficacy and safety in a Phase II trial in schizophrenia.
Addressing synaptic degradation in Alzheimer’s disease
Tackling Alzheimer’s disease has been a challenging feat for the pharmaceutical industry, with SoC protocols revolving around symptom management for many years.
However, the approval of Eli Lilly’s Kisunla (donanemab) and Biogen & Eisai’s subcutaneous Leqembi (lecanemab) offers new hope to early-stage Alzheimer’s patients, with both disease-modifying therapies (DMTs) gaining approval in recent years.
Despite these advancements, there are currently no approved therapies that target synaptic loss, which Spinogenix believes is a “major driver of cognitive decline and memory loss in the early stages of Alzheimer’s disease progression”.
In conversation with Clinical Trials Arena, Spinogenix’s CEO Stella Sarraf said that preventing synaptic loss could be a promising strategy in Alzheimer’s disease, as it could be employed alongside treatment with both symptom-managing cholinesterase inhibitors and DMTs such as Kisunla and Leqembi.
Sarraf added that drugs such as tazbentetol can reduce the burden of Alzheimer’s on healthcare systems, as a PET scan is not required to determine if the drug is suitable for a patient; instead, only a general diagnosis is required.
According to Philippa Salter, managing neurology analyst at GlobalData, key opinion leaders (KOLs) have previously highlighted the important unmet need in the Alzheimer’s market for effective drugs which target cognition.
Salter said: “If the positive results can be replicated in a large, pivotal, placebo-controlled trial, then tazbentetol has the potential to meet this unmet need.
“As an oral drug with a favourable safety profile, it would be easy to incorporate into the treatment algorithm.”
