The Eli Lilly weight reduction capsule is presumably the perfect from Pfizer and Novo Nordisk

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Drug makers are struggling to capitalize on the blockbuster weight loss industry’s next big innovation: effective, convenient, and potentially affordable obesity pills.

An estimated 40% of US adults are obese, making a successful pill a huge opportunity.

It’s still too early to pick a winner, especially with pivotal data from several drug companies set to be released later this year. And for the big players, the all-important question of pricing still remains.

But for now, an experimental oral drug by Eli Lilly seems to have an advantage over pills from Novo Nordisk And Pfizer — though it may not get US approval first.

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

The pills are easier to make than injections, which come in the form of disposable pens. That means the oral drugs could potentially help alleviate the supply shortages that their injectable counterparts suffer from.

Pills are also usually cheaper than injections, although it’s unclear if this will be the case with obesity pills.

Wegovy’s list price is over $1,300 per month plan and Ozempic’s is around $935. Novo Nordisk offers a low-dose oral version of Semaglutide that has the same list price as Ozempic for a 30-pill monthly supply. Marketed as Rybelsus, this pill is only approved for type 2 diabetes.

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

Novo Nordisk has an important advantage: the Danish company has already released results from phase three clinical trials for its high-dose version of oral semaglutide intended for weight management, and told CNBC that it expects to receive approval for the new drug later this year Food and Drug Administration to submit year.

Eli Lilly is still in the midst of Phase 3 clinical trials for its oral drug Orforglipron, which means it’s likely to come to market later.

Still, analysts are confident that orforglipron will have a competitive edge over the long term, especially after Eli Lilly last week presented results from Phase 2 clinical trials that showed the drug’s strong efficacy profile.

Strong efficacy profile

According to Eli Lilly’s phase 2 results, overweight or obese patients taking orforglipron 45 milligrams once daily lost up to 14.7% of their body weight after 36 weeks. In comparison, weight loss was 2.3% in people who received a placebo.

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

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

Geoff Meacham, an analyst at Bank of America, said in a Sunday research note that Eli Lilly’s available orforglipron data “compares fairly favorably with Novo Nordisk’s oral semaglutide, barring caveats in cross-study comparisons.”

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

“The more you take these drugs, the greater the weight loss until it reaches a plateau, right?” Chen said. “So the thought is, if you get pretty close to the weight loss of semaglutide with orforglipron in almost half the time that you’re taking orforglipron, you’re likely to exceed it.”

Chen said the hope is that orforglipron will result in a reduction similar to Eli Lilly’s tirzepatide injection, which results in about 22% weight loss after 72 weeks.

The company’s phase III clinical trials of orforglipron are investigating the drug over longer periods of time.

At least for the time being, analysts think Eli Lilly’s pill could also potentially prevail over Pfizer’s GLP-1 oral tablet 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 an average of about 10 pounds after 16 weeks, according to the results of a phase 2 clinical trial.

It is difficult to compare the effectiveness of danugliprone to that of other oral GLP-1 preparations due to different patient populations and a lack of longer-term data on the drug.

A Pfizer spokesperson told CNBC that the company is still evaluating the drug in additional Phase 2 clinical trials and “would also look to have longer data in the future” beyond the 16-week mark.

user friendliness

Wells Fargo analyst Mohit Bansal said in a research note that because of Eli Lilly’s strong orforglipron data, Pfizer’s danuglipron will stand ahead of the competition in the oral GLP-1 market.

He added that doctors generally prefer once-daily pills – like orforglipron – to twice-daily drugs like danuglipron.

Healthcare experts seem to agree: “Patient compliance increases significantly when it comes to a once-a-day pill, so that’s definitely a huge benefit. People often end up missing a few times a week when they have to take something twice a day,” said Dr. John Yoon, Professor of Endocrinology at UC Davis Health.

Pfizer is developing a once-daily version of Danuglipron.

The company also announced Monday it would halt development of another experimental pill, Lotiglipron, which Bansal said is the “more attractive GLP-1” in Pfizer’s portfolio because it’s only taken once a day. Pfizer shares fell 5% Monday after the news.

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

According to the FDA label for the low-dose, approved version of the drug, patients must take Novo Nordisk’s oral semaglutide in the morning on an empty stomach with no more than 100 mL of plain water. You will be instructed to wait 30 minutes before eating, drinking, or taking any other oral medication.

That’s because Novo Nordisk’s oral semaglutide is a peptide drug that’s harder to absorb from the gut, according to Dr. Eduardo Grunvald, medical director of UC San Diego’s Center for Advanced Weight Management.

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

He said the Eli Lilly and Pfizer pills are non-peptide GLP-1 tablets that are more easily absorbed and do not require dietary restrictions.

Cantor Fitzgerald’s Chen said market research suggests these limitations are a “major disadvantage for patients,” making Eli Lilly’s and Pfizer’s pills 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 practical use as a once-a-day pill with no dietary restrictions.

However, Chen stressed that the data released later this year could potentially change that: “Save some space for the new data to come.”

For health professionals like Grunvald, picking a winner in the oral weight-loss drug space is less important.

“I think these oral GLP-1s mean we have more tools in our toolbox and we have more options for different people who might respond differently to different drugs,” he said. “This really is the future of everything.”

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