The race for the next Ozempic is on

Two recent disappointing clinical trials of highly-anticipated weight-loss drugs have made it clear that it is too early to crown any winners in the race for the next generation of anti-obesity treatments.

Novo Nordisk’s (NVO) CagriSema and Amgen’s (AMGN) MariTide both fell short of an expected 25% average weight-loss target in late-stage trials late last year, leaving investors frustrated and sending their stock prices tumbling.

These setbacks have left the door wide open for other pharmaceutical companies racing to develop more potent weight-loss drugs. But it’s unclear how much better the next wave of treatments will be compared to those already on the market.

These medications, known commonly as GLP-1 or incretin drugs, have taken the world by storm — especially in the United States. Popularized by Ozempic, these treatments mimic gut hormones that regulate blood sugar and suppress appetite, making them highly sought after for their weight-loss effects. Popular brand names of these treatments currently on the market include Novo Nordisk’s Wegovy, which shares the same active ingredient with Ozempic, and Eli Lilly’s (LLY) Zepbound.

The weight-loss drug boom has turned Novo Nordisk and Eli Lilly into the world’s most valuable pharmaceutical companies, with sales skyrocketing in recent years. Morgan Stanley (MS) projects the global market for these treatments could hit $105 billion by 2030. In the U.S. alone, nearly 10% of the population — 31.5 million people — are expected to be using them by 2035.

With that much money at stake, it’s no surprise that drugmakers are already grinding to develop the blockbuster weight-loss drugs of tomorrow.

Faster weight loss with fewer injections and side effects

Several pharma companies are developing weight-loss drugs promising faster results and, in some cases, less frequent injections — an improvement over weekly shots like Wegovy and Zepbound. To outperform the current options, these new treatments will need to deliver weight loss exceeding 20%, the average achieved with the highest dose of Zepbound.

Novo Nordisk: The Danish pharma giant is developing a successor to its popular Ozempic medication. The company is betting that mimicking multiple hormones could deliver greater weight loss. CagriSema combines semaglutide — the active ingredient in Ozempic and Wegovy — with cagrilintide, a dual amylin and calcitonin receptor agonist, hence the name CagriSema. However, in December, Novo Nordisk said patients in a phase 3 clinical trial of the drug only lost an average of 22.7% of their body weight after 68 weeks on the medication.

Eli Lilly: The American multinational is also developing a stronger weight-loss injection, retatrutide, which, in a small clinical trial, helped patients lose 17% of their weight in 24 weeks. 

“Retatrutide is really exciting because the amount of weight loss you have seen there was even beyond tirzepatide (the active ingredient in Zepbound),” president of Lilly Cardiometabolic Health Patrik Jonsson told Quartz last year. He added this could help populations that need a greater level of weight loss.

Amgen: The pharma giant said in November that its experimental weight-loss medication, MariTide, helped patients living with obesity or who are overweight lose an average of 20% of their weight in a 52-week trial. Amgen Chief Scientific Officer James E. Bradner previously told investors that MariTide is expected to be sold in a “convenient, handheld, patient-friendly auto-injector device with a monthly or even less frequent single-injection administration.”

Viking Therapeutics (VKTX): This summer, Viking Therapeutics said it was advancing its experimental weight-loss drug, VK2735, to a late-stage clinical trial. An earlier, smaller trial found that VK2735 helped users achieve an average weight loss of 14% from baseline numbers, plus 13% compared with a placebo after 13 weeks of treatment.

Zealand Pharma: The Denmark-based drugmaker said that only about a third of patients who took up to 4.8-milligram doses of its drug petrelintide during an early-stage clinical trial experienced nausea — one of the most common side effects of popular GLP-1 weight-loss drugs. Zealand is pitching petrelinde as an alternative for patients who can’t tolerate GLP-1 treatments, which can include common side effects like nausea, vomiting, diarrhea, and abdominal pain. Zealand previously reported in June that patients taking a high dose of petrelintide over 16 weeks lost, on average, 8.6% of their weight.

An effective weight-loss pill

Pharma companies are also developing weight-loss pills that could potentially open the market for patients who are resistant to needles and are likely to be easier to manufacture helping meet growing demand and avoid shortages.

Novo Nordisk: Novo Nordisk said in September that patients who took a once-daily 50mg dose of its experimental pill amycretin lost an average of 10.4% of their weight in just three months. Trial participants who took two pills lost even more weight, 13.1% at three months. For comparison, a large clinical trial of Wegovy found that it helped users lose about 15% of their body weight over 68 weeks. It’s important to note that larger phase 2, 3, and 4 trials involving thousands more participants could return different results.

Eli Lilly: Eli Lilly is also developing a weight-loss pill — orforglipron. The drug is currently in a phase 3 trial — its results will be published this year. Earlier trials found that it helped users lose an average of nearly 15% of weight after 36 weeks.

Pfizer (PFE): Pfizer CEO Albert Bourla told analysts last fall that the company still expects its leading weight loss drug candidate, danuglipron, to be the second incretin weight-loss pill to enter the market. Pfizer announced in July it was advancing the development of danuglipron, a pill that mimics the gut hormone GLP-1. In December, the pharma giant said that a twice-daily version of the pill helped patients, in an early-stage trial, lose an average of 8% to 13% of their weight. However, the company decided not to advance this formulation to a late-stage trial due to a high rate of side effects.

Viking Therapeutics: In November, Viking Therapeutics reported that in a small phase 1 clinical study, patients who took a daily 100mg dose of Viking’s weight-loss pill lost an average of up to 6.8% of their body weight over 28 days when adjusted for those taking a placebo. This result outperformed Novo Nordisk’s amycretin.