With a quarter of the world’s population is expected to suffer from obesity by 2035, and the obesity drug market is expected to reach $131 billion in the next five years. It’s no surprise, then, that the disease is one of the biopharma industry’s hottest targets. While the market is currently dominated by Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, there are several other candidates in the pipeline whose manufacturers are aiming to secure a piece of the lucrative pie.

While the effectiveness of the GLP-1 class of anti-obesity drugs well documentedGraig Suvannevejh, senior biopharma and biotechnology equity analyst at Mizuho Americas, noted that there is still unmet demand. In an interview with BioSpaceHe has divided future developments into four categories: drugs with better safety and tolerability, those that can induce greater weight loss, oral options instead of today’s injectable drugs, and therapies that are less stressful on the muscles.

Several companies – including Novo – expect to release key data before the end of 2024. BioSpace takes a closer look at five of them.

CagriSema from Novo Nordisk

Phase III

Novo Nordisk brought ashore 1.7 billion US dollars from Wegovy in the second quarter of 2024, but the GLP-1 powerhouse is not resting on its laurels. Instead, Novo has pipeline full of candidates for the treatment of obesity, 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 analogue that promotes weight loss by delaying gastric emptying and lowering blood sugar levels. Suvannevejh noted that combination approaches could “hopefully lead to even greater weight loss.”

In August 2022, Novo Results of a Phase II study In overweight people with type 2 diabetes, CagriSema was shown to achieve a weight reduction of 15.6% over 32 weeks, compared with a reduction of 5.1% with Wegovy alone and an 8.1% reduction with cagrilintide alone.

CagriSema also competes directly with Lilly’s Zepbound. Phase III study which began in November 2023. The study, which will enroll 800 people, is scheduled to be completed in August 2025, according to Clinicaltrials.gov.

MariTide by Amgen

Phase II

During a first quarter 2024 earnings report in May, Amgen CSO James Bradner said expressed confidence in MariTide, the company’s next-generation obesity candidate. At the time, Amgen claimed positive Phase II results for MariTide but did not provide details. Investors and other obesity observers may get a clearer picture later this year, when Amgen is expected to report an interim Phase II analysis.

MariTide is an injectable bispecific molecule that can simultaneously inhibit the GIP receptor and activate the GLP-1 receptor. Data from Phase I for the candidate, published in Februaryshowed that MariTide was able to reduce the body weight of overweight participants without diabetes by 14.5% after 85 days. These data also suggest that the experimental treatment could have longer-lasting effects than currently available GLP-1 treatments, according to Amgen.

Suvannevejh called MariTide “an extremely high-profile program” for Amgen investors, noting that the company’s recent share price fluctuations were largely due to its ownership of an anti-obesity drug.

Monlunabant from Novo Nordisk

Phase II

In August 2023, Novo Nordisk provided more than $1 billion to acquire Inversago Pharma and its lead product, INV-202, now known as monlunabant. Novo will have an opportunity to assess the value of this purchase 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 regulating metabolism and appetite. According to Novo’s acquisition announcement, CB1 is widely expressed in peripheral tissues – including the kidney and liver – and blocking this receptor has demonstrated therapeutic effects in a variety of cardiometabolic and fibrotic diseases in preclinical studies.

Suvannevejh said the upcoming data is “relatively eagerly awaited” and the results could also have implications for the fortunes of two other companies focused on the CB1 receptor, Corbus Pharmaceuticals and Skye Bioscience.

He noted that there have been concerns in the past about the safety profile of this class of drugs, particularly the risk of suicide. However, Suvannevejh said, “The fact that Novo shelled out over a billion dollars suggests that either suicidality was never really a problem… or that this next generation of drugs has somehow figured it out and developed around suicidality.”

APHD-012 from Aphaia Pharma

Phase II

Multinational biopharmaceutical company Aphaia Pharma is developing APHD-012, a proprietary oral glucose formulation to restore endogenous nutrient sensing pathways in the gastrointestinal tract.

APHD-012 is designed to “reactivate the nutrient-sensing cells in the gut that are under-used in the complex pathology associated with obesity,” explained Steffen-Sebastian Bolz, chief scientific officer at Aphaia. “APHD-012 has a broad metabolic effect by restoring the release of the full spectrum of nutrient-related hormones,” he said. BioSpace in an email.

Aphaia expects a wealth of topline data from a Phase II study of APHD-012, with results from Arm 1 of the study expected in the third quarter and Arm 2 in the fourth quarter. In June, the company announced Registration for the second part of the study was completed.

Bolz said The Phase I and II studies showed “very benign side effect profiles” that could encourage long-term use of the drug in order to “permanently restore metabolic balance and achieve effective chronic weight control.”

TERN-601 from Terns Pharmaceuticals

Phase I

In the area of ​​oral GLP-1 treatment, California-based biotech company Terns Pharmaceuticals expects topline Phase I data for its lead obesity candidate TERN-601 in the second half of this year. In a study published in November 2023, Press release In announcing the dosing for the first participant in the Phase I trial, Terns noted that these results would provide proof of concept data for the candidate, an oral GLP-1 receptor agonist.

Although it is still early stages, most investors in the obesity space have looked to the Phase I data as an indicator of the drug’s overall quality, Suvannevejh said. First, he said, that’s because a safety and tolerability report is particularly important for a GLP-1 class that has had tolerability issues. “But perhaps more importantly, you get an initial, albeit only 28-day, report on efficacy.”