With the smash success of glucagon-like peptide-1 (GLP-1) agonists as a treatment for obesity, pharmaceutical giants and emerging biotechnology firms alike are working to develop an equally effective option in the form of pills.
The weight loss drug market, projected by Goldman Sachs to reach $130 billion by 2030, represents a significant opportunity for drugmakers.
While several oral weight loss therapies have been approved by the US Food and Drug Administration, none are GLP-1 agonists.
GLP-1 agonists mimic the natural hormone glucagon-like peptide-1 to manage blood sugar levels, reduce appetite, and promote weight loss, with a relatively favorable side effect profile.
GLP-1 agonists are typically administered via injections with the development of an oral version promising to be a more convenient and potentially cheaper option for consumers.
At the same time, emerging biotechnology companies are exploring entirely new mechanisms beyond GLP-1 to tackle obesity in the consumer-friendly oral format.
Big pharma’s push
Novo Nordisk (NYSE:NVO) is developing an oral form of semaglutide, the active ingredient in its blockbuster weight loss brands Ozempic and Wegovy. A phase 3 study of oral semaglutide in participants with obesity showed an average weight loss of 15% after 68 weeks, with 34% seeing a 20% drop in their weight.
Novo Nordisk is also developing an oral dual agonist of GLP-1 and amylin receptors called amycretin, which achieved a 13.1% weight loss in a Phase 1 trial after 12 weeks.
Zepbound-maker Eli Lilly and Co (NYSE:LLY), meanwhile, is developing an oral medication targeting GLP-1 called orforglipron with promising results to date. In a Phase 2 trial, participants achieved an average weight loss between 9% to 15% over 36 weeks.
Pfizer Inc (NYSE:PFE, ETR:PFE) is also developing a once-daily GLP-1 agonist danuglipron, which is set to undergo dose optimization studies in the second half of 2024 after gastrointestinal side effects saw high discontinuation rates in a Phase 2b trial.
Emerging biotechs enter the race
Small and mid-cap firms are also taking part in the race to develop oral weight loss therapies, challenging the dominance of big pharma in this market.
Viking Therapeutics (NASDAQ:VKTX) is uniquely positioned with its drug candidate VK2735, a dual agonist of the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. The company has initiated a Phase 2 safety and efficacy trial in patients with obesity after a Phase 1 study demonstrated promising weight loss and tolerability. Higher doses showed greater efficacy, with 57% of patients achieving a 5% or more body weight reduction at the 40-mg dose.
Also entering the race is Biolexis Therapeutics with its small molecule BLX-7006. It demonstrated significant weight loss efficacy in a diet-induced obesity study involving mice, achieving an average weight reduction of 15% over a 28-day period.
Another oral small molecule that has shown promise in addressing weight loss is Immunic Inc (NASDAQ:IMUX)’s IMU-856. Rather than mimicking GLP-1, IMU-856 targets SIRT6, a protein involved in regulating cellular processes, including metabolism and intestinal barrier function.
Dr Daniel Vitt told Proactive the data shows IMU-856 could offer a different way to treat obesity, highlighting the need for more treatment options as obesity increasingly impacts the health system.
“Looking at the data we’ve generated so far, IMU-856 could offer a new mode of action with an oral treatment that would be easy to handle and with an attractive safety profile,” Dr Vitt said.
IMU-856 has been shown to increase endogenous GLP-1 levels in a dose-dependent manner, potentially offering benefits similar to GLP-1 agonists. In a phase 1b clinical trial for celiac disease, it boosted GLP-1 levels by up to 250% compared to placebo.
Further, a six-month preclinical study showed a dose-dependent reduction in body weight gain and food intake, with up to a 40% reduction.