Eli Lilly weight loss pill may best Pfizer, Novo Nordisk drugs

Drugmakers are jockeying to capitalize on the next major innovation coming to the blockbuster weight loss industry: effective, convenient and potentially affordable obesity pills. 

An estimated 40% of U.S. adults are obese, making a successful pill a massive opportunity.

It’s too early to crown a winner, especially since pivotal data from several pharmaceutical companies is slated to come out later this year. And there’s still the all-important issue of pricing for the major players.

But for now, one experimental oral drug from Eli Lilly appears to have an edge over pills from Novo Nordisk and Pfizer — even though it may not win U.S. approval first. 

All three manufacturers are developing oral versions of GLP-1s, a class of drug that mimics a hormone produced in the gut to suppress a person’s appetite. Novo Nordisk’s popular Wegovy and Ozempic treatments, which sparked a weight loss industry gold rush last year, are weekly GLP-1 injections also known as semaglutide.

The pills are easier to manufacture than injections, which come in the form of single-use pens. That means the oral drugs could potentially help alleviate the supply shortages plaguing their injectable counterparts. 

Pills are also typically cheaper than injections, though it’s unclear if that will be the case with the obesity pills. 

Wegovy’s list price tops $1,300 per monthly package, and Ozempic’s is about $935. Novo Nordisk has a low-dose oral version of semaglutide that has the same list price as Ozempic for a monthly package of 30 tablets. That pill, marketed as Rybelsus, is approved only for Type 2 diabetes.

None of the three drugmakers has provided estimates for how much the new obesity pills would cost. 

Novo Nordisk has one important advantage: The Danish company has already released phase three clinical trial results for its high-dose version of oral semaglutide, which is intended for weight management, and told CNBC it expects to file for Food and Drug Administration approval later this year.

Eli Lilly is still in the middle of phase three clinical trials on its oral drug, orforglipron, meaning it’s likely to hit the market later.

Still, analysts are confident in the competitive edge of orforglipron in the long run, especially after Eli Lilly unveiled phase two clinical trial results last week that showcased the drug’s strong efficacy profile.  

According to Eli Lilly’s phase two results, overweight or obese patients who took 45 milligrams of orforglipron once a day lost up to 14.7% of their body weight after 36 weeks. That compares with a weight loss of 2.3% for people who received a placebo. 

Eli Lilly’s results appear consistent with the weight reduction caused by Novo Nordisk’s pill, but were achieved over a shorter trial period.

Overweight or obese patients who took 50 milligrams of Novo Nordisk’s drug once a day saw an average weight loss of 15.1% after 68 weeks, according to phase three clinical trial results released Sunday. 

Bank of America analyst Geoff Meacham said in a Sunday research note that Eli Lilly’s available orforglipron data “compares quite favorably” to Novo Nordisk’s oral semaglutide, “cross trial comparison caveats aside.” 

Cantor Fitzgerald analyst Louise Chen told CNBC that orforglipron could potentially achieve an even greater level of weight loss over a longer trial period. 

“The more you use these drugs, the more weight loss you’ll see until it plateaus, right?” Chen said. “So the thought is, if you’re getting pretty close to semaglutide’s weight loss in almost roughly half the time with orforglipron, you will probably exceed it.” 

Chen said the hope is that orforglipron leads to a reduction similar to that of Eli Lilly’s injection tirzepatide, which resulted in weight loss of around 22% after 72 weeks. 

The company’s phase three clinical trials on orforglipron will study the drug over longer time periods. 

At least for now, analysts say Eli Lilly’s pill may also have the upper hand over Pfizer’s oral GLP-1, danuglipron, which is still in phase two clinical trials.

Patients with Type 2 diabetes who took a 120-milligram version of danuglipron twice a day lost around 10 pounds on average after 16 weeks, according to results from one phase two clinical trial.

It’s difficult to compare danuglipron’s efficacy with that of other oral GLP-1s due to differing patient populations and the lack of longer-term data on the drug. 

A Pfizer spokesperson told CNBC that the company is still studying the drug in further phase two clinical trials and “would also look to have longer data” beyond the 16-week mark in the future. 

Wells Fargo analyst Mohit Bansal said in a research note that Pfizer’s danuglipron will be challenged to compete in the oral GLP-1 space given Eli Lilly’s strong orforglipron data. 

He added that physicians generally prefer once-daily pills — like orforglipron — over twice-daily drugs such as danuglipron. 

Health experts seem to agree: “Patient compliance increases a lot if it’s a once-a-day pill, so it’s definitely a big advantage. People often end up missing a few times a week if they have to take something twice a day,” said Dr. John Yoon, an endocrinology professor at UC Davis Health. 

Pfizer is developing a once-daily version of danuglipron.

The company on Monday also said it would stop developing another experimental pill, lotiglipron, which Bansal said had been the “more attractive GLP-1” in Pfizer’s portfolio since it’s only taken once a day. Shares of Pfizer fell 5% on Monday following that news.

But Pfizer and Eli Lilly do share one key advantage over Novo Nordisk’s oral semaglutide: no dietary restrictions. 

Patients need to take Novo Nordisk’s oral semaglutide in the morning on an empty stomach with no more than four ounces of plain water, according to the FDA label for the low-dose, approved version of the drug. They’re instructed to wait 30 minutes before eating, drinking or taking other oral medicines.

That’s because Novo Nordisk’s oral semaglutide is a peptide medication, which is more difficult for the gut to absorb, according to Dr. Eduardo Grunvald, medical director for UC San Diego’s Center for Advanced Weight Management.

“If you take it with food or drink, it just won’t get absorbed efficiently,” Grunvald told CNBC.

He said pills from Eli Lilly and Pfizer are non-peptide GLP-1s, which are absorbed more easily and don’t require dietary restrictions. 

Cantor Fitzgerald’s Chen said market research suggests that those restrictions are a “big negative for patients,” making the pills from Eli Lilly and Pfizer convenient alternatives. 

Overall, Eli Lilly’s orforglipron appears to be the top contender in the weight loss pill space due to its strong efficacy data and convenience as a once-daily pill without dietary restrictions. 

But Chen emphasized that the data unveiled later this year could potentially change that: “Save some room for the new data coming.” 

For health experts such as Grunvald, naming a winner in the oral weight loss drug space is less important.

“I think these oral GLP-1s mean having more tools in our toolbox, having more options for different people who might react differently to different medicines,” he said. “That’s really the future of this all.”