Sosei Group and Allergan, its license partner for HTL0018318, have decided to voluntarily suspend clinical development activities with HTL0018318 pending the investigation of an unexpected toxicology finding in an animal study involving non-human primates. This voluntary suspension is not based on any human findings.
Sosei's programs with other partners as well as its in-house pipeline are not impacted by the finding.
HTL0018318 is a selective small molecule muscarinic M1 receptor agonist under clinical investigation as a potential new symptomatic treatment for cognitive impairment in patients with Alzheimer's disease (AD) and other dementias, including dementia with Lewy bodies, (DLB). The compound is in Phase 1 clinical development in the US (sponsored by Allergan), and in a Phase 2 clinical study in Japan in patients with DLB. A further Phase 1b study in AD patients has completed its clinical phase in Europe and the data is being analyzed (sponsored by Sosei's subsidiary Heptares Therapeutics).
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To date, HTL0018318 has been investigated in approximately 310 human subjects in the US and Europe, including healthy volunteers and patients with mild/moderate AD. Data available from the human studies have found it to be well tolerated and with no serious adverse effects at the tested doses for up to 28 days.
The decision by Sosei and Allergan to voluntarily suspend clinical development activities with HTL0018318 was taken as a precaution based on emerging results from a single animal toxicology study in non-human primates. This animal toxicology study was investigating different dosing levels of HTL0018318 over a nine-month period. The toxicological finding (neoplastic, rare tumor) was observed at doses and durations exceeding those used clinically in humans to date. No serious safety findings were observed in any species in any other animal toxicology studies with HTL0018318 extending as long as six months. Scientists from both Sosei and Allergan will be investigating these findings, which are currently of unknown cause.
Sosei and Allergan have reported the safety finding of the study to the US Food & Drug Administration (FDA) and the Japan Pharmaceutical & Medical Devices Agency (PMDA). Other regulatory authorities in countries where studies that have been completed were also informed. Sosei is undertaking a thorough investigation to identify the significance and cause of the safety finding and determine the next steps. Data from previous preclinical and clinical studies will be reviewed as part of the investigation.
"We were very surprised to see these results given the safety profile HTL0018318 has exhibited across all previous animal and clinical studies. We have taken these steps in the best interests of patient safety, which is our number one priority,” Dr. Tim Tasker, Chief Medical Officer of Sosei, said. “We are committed to working with clinical investigators, R&D teams and regulatory authorities to understand better the reason for the findings from this animal toxicology study and so enable the human clinical development program with HTL0018318 to continue as soon as possible. We remain confident that this compound has the potential to deliver important benefits to patients with AD and DLB.”