Skye Biosciences’ glucagon-like peptide 1 receptor agonist (GLP-1RA) alternative has failed to show efficacy as a monotherapy in obesity, dashing its chance as a competitor of blockbuster drugs Zepbound (tirzepatide) and Wegovy (semaglutide).
During the Phase IIa trial (NCT06577090), the peripheral cannabinoid receptor 1 (CB1) inhibitor, nimacimab, did not significantly boost weight loss, achieving a 1.52% reduction as opposed to the 0.26% increase seen in the placebo cohort.
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However, in the topline readout, Skye noted that this was likely due to the 200mg chosen dose, which the San Diego-based biotech claimed was “suboptimal as a monotherapy”. Skye claimed this due to the observed association between exposure to the drug and patient response.
To combat this issue in further studies, Skye is considering testing doses of 600mg – 1000mg, though this would boost the injection burden for patients, noted Andy T. Hsieh, biotech equity research analyst at William Blair.
Though nimacimab monotherapy was not effective on its own, it did show promise when paired with Novo Nordisk’s star GLP-1RA, Wegovy.
After 26 weeks of treatment, patients given the combination lost significantly more body mass than those in the Wegovy monotherapy arm – demonstrating weight loss of -13.2%. This was 2.95% more than the 10.25% drop seen in Wegovy-only patients.
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By GlobalDataNimacimab also enhanced the frequency of responders when used in combination with Wegovy, triggering weight loss of 10% or higher in 67% of patients compared with the 50% seen in the Wegovy monotherapy arm.
Meanwhile, the drug was proven tolerable and safe, as there were no additional gastrointestinal (GI) or neuropsychiatric adverse events (AEs) associated with the addition of nimacimab to the standard Wegovy regimen.
According to Sean Wharton, Director of the Wharton Medical Clinic and clinical advisor to Skye, the Phase IIa topline results warrant further studies with “higher nimacimab dosing,” as this would help to fully define the drug’s potential role in obesity.
However, investors do not seem enamoured by the concept, as Skye’s stock value crashed by 61% to $1.83 at market open after the news debuted on 6 October. This is down from $4.75 at market close on 3 October.
Analysts “intrigued” by Skye’s obesity candidate
Despite nimacimab failing to meet investor expectations when used as a monotherapy for obesity, Hsieh noted that he was “encouraged” by activity in the nimacimab-Wegovy combination group.
“The combination of nimacimab plus Wegovy demonstrated a rough 3.0% separation over Wegovy monotherapy,” he stated.
Hsieh added: “Though speculative in nature, we are encouraged that the weight loss curve continues to separate over time for both nimacimab plus Wegovy combination”. This was also seen for nimacimab monotherapy compared to Wegovy monotherapy and placebo, respectively”.
Meanwhile, key opinion leaders (KOLs) Dr Wharton and Louis Aronne, past chair of the American Board of Obesity Medicine and clinical advisor to Skye, noted that a low-dose GLP-1RA like Wegovy or Zepbound plus a modality that does not contribute to GI AEs could combat high patient discontinuation rates.
This is because the combination could potentially “drive more substantial weight loss”, while maintaining patients on therapy.
Though the future of Skye’s drug in obesity may be hanging in the balance, if it were to get the regulatory go-ahead, it would be entering a rapidly growing market.
Analysts at GlobalData, parent company of Clinical Trials Arena, forecast that the sector will be worth $206.5bn by 2031 – up more than 1500% from its $12.3bn value in 2021.
