Sufferers dosed with an experimental Skye Bioscience weight problems drug did not lose enough weight to fulfill the objectives of a mid-stage research, dealing a setback to the biotech’s bid to revive a category of medicines as soon as written off on account of security dangers. These issues didn’t emerge within the medical trial, which Skye executives say recommend the drug might but show profitable with larger dosing.
The Skye drug, nimacimab, is an antibody designed to dam CB1, a receptor whose physiological roles embrace regulating urge for food. San Diego-based Skye is evaluating the weekly injectable drug in a 136-patient Part 2a research. The preliminary outcomes reported Monday present individuals who obtained Skye’s nimacimab as a monotherapy misplaced a mean 1.52% of their physique weight after 26 weeks in comparison with 0.26% weight reduction for the placebo arm — not sufficient to be statistically vital.
The mixture of the research drug with Novo Nordisk’s Wegovy was higher, reaching a clinically significant common 13.2% loss in weight in comparison with 10.25% within the arm that obtained Wegovy and a placebo. Whereas these outcomes fell in need of statistical significance, weight reduction didn’t plateau at 26 weeks, which the corporate stated signifies sufferers may proceed to lose extra weight with longer dosing.
Skye shares opened Monday at $1.81 every, down practically 62% from Friday’s closing worth.
CB1 has each medical and regulatory validation from Sanofi, which obtained European approval in 2006 for rimonabant, an oral small molecule inhibitor of the goal. Whereas concentrating on CB1 within the gastrointestinal tract may also help sufferers shed some pounds, this receptor can also be discovered within the central nervous system. Rimonabant hit these receptors within the mind, resulting in suicidal ideation in some sufferers. In 2008, Sanofi withdrew the drug from the market.
Skye designed nimacimab to be peripherally restricted, blocking CB1 within the gastrointestinal tract however avoiding the CNS. In an interview final 12 months, Chief Development Officer Tu Diep explained that as an antibody, nimacimab is too large to penetrate the blood-brain barrier — which ought to keep away from inflicting the complication dangers noticed with rimonabant. Within the Part 2a outcomes, Skye stated nimacimab alone and together with Wegovy confirmed a clear security profile. Not solely had been there no further gastrointestinal unintended effects, there have been additionally no neuropsychiatric opposed occasions reported.
Sufferers who accomplished the 26-week research had been eligible to enroll in a 26-week extension research. Enrollment is full and Skye expects information shall be out there within the first quarter of subsequent 12 months. Extra detailed outcomes from the preliminary 26-week interval shall be offered subsequent month throughout the ObesityWeek convention in Atlanta.
The 200 mg, once-weekly dose was primarily based on modeling from Part 1 testing suggesting vital peripheral publicity of the drug however little to no publicity within the mind, Skye stated in an investor presentation. The corporate stated preclinical information and modeling of the nimacimab’s pharmacokinetics (PK) — how the physique interacts with the drug all through its publicity within the physique — point out the drug’s potential at larger doses.
“With our preclinical information, toxicology security margins, and PK modeling, we imagine we’ve a path to help larger dosing, and we’re evaluating the following stage of improvement to optimize dosing in potential future medical trials,” Chief Medical Officer Puneet Arora stated within the Skye announcement.
Skye is attempting to set itself aside in a small group of firms working to revive CB1 inhibition as a technique to deal with weight problems. Novo Nordisk’s 2023 acquisition of Inversago Pharma introduced a lead program, now known as monlunabant, that’s an oral small molecule inhibitor of CB1. Whereas this drug has mid-stage information exhibiting statistically vital weight reduction, results showed neuropsychiatric effects. Corbus Prescription drugs’ CRB-913 can also be a peripherally restricted oral small molecule inhibitor of CB-1; the corporate expects to start a Part 1b dose-ranging research within the fourth quarter of this 12 months.
Skye stated within the investor presentation it is going to give attention to a mix technique with Wegovy whereas persevering with to guage larger doses of nimacimab as a monotherapy. The corporate will even assess nimacimab’s potential as a upkeep remedy for sufferers who’ve achieved goal weight reduction with a GLP-1 weight reduction drug. Within the medical trial outcomes up to now, nimacimab didn’t improve the frequency or severity of gastrointestinal unintended effects which are a typical cause cited for discontinuing remedy. That might give the Skye drug a security and tolerability benefit over continual use of GLP-1 medication.
For Skye to proceed with larger dosing of nimacimab as a monotherapy, William Blair analyst Andy Hsieh stated it’s crucial to cut back the affected person dosing burden, which is presently two injections, 100 mg per syringe. Hsieh is extra intrigued by the Skye drug’s potential use together with Wegovy. The outcomes present that the 2 medication collectively led to a 13% placebo-adjusted weight reduction, which was throughout the double-digit vary that Skye had set and confirmed separation from remedy with Wegovy alone, he stated in a observe despatched to buyers.
“We’re dissatisfied by the medical setback of nimacimab,” Hsieh wrote. “Nevertheless, we’re hopeful that with larger doses (akin to 600 mg or 1,000 mg per week), nimacimab may present extra substantial monotherapy exercise and intensify its capacity to be mixed with Wegovy.”
Photograph: Peter Dazeley, Getty Photographs
