Eli Lilly Biotechnology Center is shown in San Diego, California, U.S. March 1, 2023.
Mike Blake | Reuters
Eli Lilly on Tuesday said its daily weight loss pill helped patients with obesity and Type 2 diabetes shed weight in a late-stage trial, meeting the study’s main goal and clearing the way for the company to file for approval of the drug globally.
The treatment is inching closer to becoming a new, needle-free alternative in the highly lucrative market for weight loss and diabetes drugs called GLP-1s. More convenient pills could boost supply for the treatments and make them easier to access than the pricey weekly injections currently dominating the space. The Eli Lilly pill also would not come with dietary restrictions, in contrast to a similar oral treatment from chief rival Novo Nordisk.
The highest dose of the pill, orforglipron, helped patients lose 10.5% of their weight, or 22.9 pounds, on average at 72 weeks, compared to 2.2% weight loss among those who took a placebo. The drug’s weight loss in the study was 9.6% when analyzing all patients regardless of discontinuations.
Eli Lilly’s pill met the trial’s other goals of helping patients lower their hemoglobin A1c, a measure of blood sugar levels. By the end of the study, most patients no longer met the criteria for Type 2 diabetes based on that metric. The rate of side effects and treatment discontinuations in the study, called ATTAIN-2, appeared to be generally consistent with two recent phase three trials on Eli Lilly’s drug.
Eli Lilly said it now has the full clinical trial data package required to file for approvals of the drug for chronic weight management with global regulators. The pharmaceutical giant expects to launch the pill around the world “this time next year,” CEO David Ricks told CNBC in early August.
In an interview, Eli Lilly’s Chief Scientific Officer Daniel Skovronsky, said the pill had “unprecedented efficacy” in patients with obesity and Type 2 diabetes, who typically have a more difficult time losing weight compared to those without diabetes. Skovronsky said he hopes that diabetes patients will be able to use the pill earlier in their disease to slow down its progression.
Existing GLP-1 injections have shown greater weight loss than Eli Lilly’s pill, but having an oral option that offers more than 10% for patients with both obesity and Type 2 diabetes is “actually very good, so that’s positive,” said Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital.
But she called it “concerning” that more patients – 10.6% of those on the highest dose – stopped taking the pill due to side effects compared with what has been seen in separate studies on the existing injections, Eli Lilly’s Zepbound and Novo Nordisk‘s Wegovy. Apovian said patients and their prescribers will have to weigh the risks and benefits of the pill and the injections when deciding which to take, including convenience, side effects and efficacy.
The side effects of Eli Lilly’s pill were mainly gastrointestinal, such as nausea and vomiting, and were mild to moderate in severity. An estimated 23.1% of those who took the highest dose experienced vomiting, while 36.4% and 27.4% had nausea and diarrhea, respectively.
Around 20% of patients stopped taking the pill for any reason, which is roughly the same rate as the placebo group. Skovronsky said that reflects a combination of reasons apart from side effects. Those can include patients who wanted to stop participating in a trial because they were able to access another obesity medication, or those who didn’t lose enough weight because they were taking a lower dose of the drug.
But he said most patients stay on the drug, and said “the most important thing here is the scale of the opportunity,” referring to the number of people around the world could benefit from orforglipron. More than 100 million adults in the U.S. alone have obesity, according to Centers for Disease Control and Prevention data.
Apovian said she’s most excited about an oral option entering the market not because of how much weight loss it can promote, but rather its potential to expand access to obesity treatments, especially since a pill is much easier to manufacture than an injection. Apovian hopes Eli Lilly’s pill will be priced lower than injections — which cost roughly $1,000 per month before insurance — and receive broader insurance coverage.
Tuesday’s results are the third set of late-stage data the company has released on orforglipron this year. In April, the pill succeeded in a shorter phase three trial on diabetes patients without obesity.
Earlier this month, the drug also met the goals of a separate study on patients with obesity and not diabetes, but fell short of Wall Street’s expectations. The pill’s weight loss was higher in that trial compared to Tuesday’s data, but “that’s expected,” given the differences in patient populations, said Dr. Jaime Almandoz, medical director of the Weight Wellness Program at UT Southwestern Medical Center.
Overall, some doctors have touted the pill’s weight loss in the trials, and some analysts say it will still be a viable competitor in the space due to factors such as its easier manufacturing and lack of dietary restrictions.
“The convenience and specifically the lack of fasting requirements and water restrictions with orforglipron is likely one of the main differentiators when people think about other oral agents with similar effectiveness for weight change and A1C levels,” said Almandoz.
He said a pill creates additional opportunities for individualized patient care “where there’s more autonomy.” For example, some people may be hesitant to take injections for weight loss.
Detailed trial data
The trial followed more than 1,600 people, who were randomized to receive three different target doses of Eli Lilly’s pill or a placebo. Patients started at a lower dose of the drug and gradually increased it at four-week intervals to reach their final target dose.
More than 50% of patients on the highest dose of Eli Lilly’s treatment lost at least 10% of their weight in the trial, while 28.4% of those participants lost at least 15%. Across the different groups, the company did not disclose how many patients lost at least 5% of their weight.
Orforglipron “may not be the answer” for patients who are morbidly overweight, said Howard Weintraub, clinical director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart. But he said, “for a lot of people who need to lose a fair amount of weight, losing 10% can make a big diference.”
Orforglipron lowered A1C by an average of 1.3% to 1.8% across different doses at 72 weeks, from a starting level of 8.1%. Around 75% of participants taking the highest dose achieved an A1C of 6.5% or less, which is at or below what the American Diabetes Association defines as diabetes.
Eli Lilly’s pill also improved key cardiovascular risk factors.
“We now have study after study with GLP-1 agonists showing that they reduce very important outcomes, which is what I do every day as a preventive cardiologist,” Weintraub said. “I try my very best to prevent them from having heart attack, stroke and death.”
Eli Lilly’s pill works in a similar way to Wegovy, Ozempic and Novo Nordisk’s diabetes pill Rybelsus, targeting a gut hormone called GLP-1 to suppress a person’s appetite and regulate blood sugar. Novo Nordisk is also seeking approval of an oral version of Wegovy, which could come by year-end.
But unlike those three medications, Eli Lilly’s pill is not a peptide medication. That means it is absorbed more easily by the body and does not require dietary restrictions like Rybelsus or oral Wegovy does.
