Hundreds of companies are currently running clinical trials in the increasingly lucrative obesity space. BioSpace looks at five candidates with data expected before the end of the year.
With a quarter of the world’s population expected to have obesity by 2035 and the market for obesity therapeutics predicted to hit $131 billion within the next five years, it’s no wonder the disease is one of biopharma’s hottest targets. While the space is currently dominated by Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, several other candidates are making their way through the pipeline, their makers aiming to snag a piece of the lucrative pie.
While the efficacy of the GLP-1 class of medicines for obesity is well-documented, Graig Suvannevejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, noted that there are still unmet needs. In an interview with BioSpace, he put future developments into four categories: drugs that have better safety and tolerability, those that can elicit greater weight loss, oral options instead of today’s injectables and therapies that are muscle-sparing.
Several companies—Novo included—are anticipating key data readouts before the end of 2024. BioSpace takes a closer look at five of these.
Novo Nordisk’s CagriSema
Phase III
Novo Nordisk reeled in $1.7 billion from Wegovy in the second quarter of 2024, but the GLP-1 powerhouse isn’t resting on this success. Instead, Novo has a pipeline full of obesity candidates, including CagriSema, for which Phase III results are expected in the second half of 2024, according to Mizuho.
CagriSema combines Wegovy with cagrilintide, a long-acting amylin analog that promotes weight loss by delaying gastric emptying and lowering blood glucose levels. Suvannevejh noted that combination approaches could lead to “hopefully even greater weight loss.”
In August 2022, Novo posted results from a Phase II study in overweight individuals with type 2 diabetes, showing that CagriSema could elicit a 15.6% body weight reduction over 32 weeks, compared to a 5.1% reduction with Wegovy alone and an 8.1% reduction with cagrilintide alone.
CagriSema is also going up against Lilly’s Zepbound in a head-to-head Phase III trial that kicked off in November 2023. The trial, which is targeting enrollment of 800 people, is slated to be completed in August 2025, according to Clinicaltrials.gov.
Amgen’s MariTide
Phase II
During a first-quarter 2024 earnings report in May, Amgen CSO James Bradner expressed confidence in the company’s next-generation obesity candidate MariTide. At the time, Amgen said the candidate had a differentiated profile but did not reveal further details. Investors and other obesity space watchers could get a clearer picture later this year when Amgen is expected to provide an interim Phase II analysis.
MariTide is an injectable bispecific molecule that can simultaneously inhibit the GIP receptor and activate the GLP-1 receptor. Phase I data for the candidate, published in February, showed that MariTide could reduce body weight by 14.5% after 85 days in obese participants without diabetes. These data also suggest the investigational treatment could have longer-lasting effects than currently available GLP-1 treatments, according to Amgen.
Suvannevejh called MariTide “a very high-profile program” for Amgen investors, noting that a lot of the more recent movement in the company’s stock is owing to its possession of an obesity drug.
Novo Nordisk’s Monlunabant
Phase II
In August 2023, Novo Nordisk put up more than $1 billion to acquire Inversago Pharma and its lead asset, INV-202, now known as monlunabant. Novo will have an opportunity to gauge the value of this buy in the second half of 2024, when Phase II data from the candidate are expected.
Monlunabant is an oral blocker of the cannabinoid receptor 1 (CB1 receptor), which is important for the regulation of metabolism and appetite. According to Novo’s acquisition announcement, CB1 is commonly found on peripheral tissues—including the kidneys and liver—and blocking this receptor has been shown in preclinical studies to have therapeutic effects across a wide range of cardiometabolic and fibrotic diseases.
Suvannevejh said the upcoming data are “relatively highly anticipated” and that the results could also have an impact on the fortunes of two other companies targeting the CB1 receptor, Corbus Pharmaceuticals and Skye Bioscience.
He noted that there have been concerns in the past regarding the safety profile of this drug class, specifically the risk of suicidality. However, Suvannevejh said, “the fact that Novo plunked down over a billion dollars would seem to suggest that perhaps either this suicidality never really was an issue to begin with . . . or this next generation of drugs have kind of figured it out and kind of engineered around the suicidality.”
Aphaia Pharma’s APHD-012
Phase II
Multinational biopharma company Aphaia Pharma is developing APHD-012, a proprietary oral glucose formulation designed to restore endogenous nutrient-sensing pathways in the gastrointestinal tract.
APHD-012 is intended to “reactivate the intestinal nutrient-sensing cells, which are underutilized as part of the complex obesity-associated pathology,” explained Steffen-Sebastian Bolz, chief scientific officer at Aphaia. “APHD-012 creates a broad metabolic impact by restoring the release of the entire spectrum of nutrient-induced hormones,” he told BioSpace in an email.
Aphaia is anticipating a wealth of topline data from a Phase II trial of APHD-012, with results from Arm 1 of the study expected in Q3 and Arm 2 in Q4. In June, the company announced it had completed enrollment in the second arm of the trial.
Bolz said the Phase I and II trials have shown “very benign adverse effect profiles” that could encourage the long-term use of the drug to “permanently restore metabolic balance and [elicit] effective chronic weight management.”
Terns Pharmaceuticals’ TERN-601
Phase I
In the oral GLP-1 bucket, California-based biotech Terns Pharmaceuticals is expecting topline Phase I data for its lead obesity candidate, TERN-601, in the second half of this year. In a November 2023 press release announcing the dosing of the first participant in the Phase I trial, Terns noted that this readout would provide “proof of concept” data for the candidate, an oral GLP-1 receptor agonist.
While in the early stage, Suvannevejh said that in the obesity space most investors have looked at Phase I data as a proxy for the overall quality of the drug. First, he said, this is because a safety and tolerability readout is especially important for a GLP-1 class in which there have been noted tolerability issues. “But perhaps more importantly, you do get an initial, albeit just 28-day, read of the efficacy.”
Correction (Aug. 12): This article has been corrected to clarify that Amgen did not specifically report positive Phase II results for MariTide. BioSpace regrets the error.
