Eli Lilly's obesity pill led to more than 12% weight loss in closely watched late-stage trial, paving way for approval

CNBC

4 days ago

Eli Lilly on Thursday said the highest dose of its daily obesity pill helped patients lose more than 12% of their body weight, or roughly 27 pounds, at 72 weeks in a late-stage trial, paving way for its entrance into the market.
Some doctors said the results appear to be comparable to, if not slightly lower, the level of weight loss seen with Novo Nordisk's blockbuster weekly GLP-1 injection for obesity, Wegovy.
The data comes under what some Wall Street analysts were expecting for Eli Lilly's oral GLP-1, with hopes for weight loss of around 15%. Some doctors also made note of the number of patients on the highest dose of the pill who discontinued treatment due to side effects or any other reason in the trial.
Still, other doctors lauded the results and the potential of the pill to reach new patients, such as those who are afraid of needles.
"This is a strong and promising result for an oral agent," said Dr. Jaime Almandoz, medical director of the Weight Wellness Program at UT Southwestern Medical Center, calling the weight loss "a significant and clinically meaningful outcome."
"Injectables have set a high bar, but this study reinforces the potential for an oral GLP-1 to be transformative in obesity care, particularly for patients who are hesitant to start or maintain injectable therapies," he continued.
Dr. Mihail "Misha" Zilbermint, director of Endocrine Hospitalists at the Johns Hopkins Community Physicians, said he believes the pill "has the potential to be a game changer, as long as people can tolerate the side effects."
The trial results are among the pharmaceutical industry's most closely watched studies of the year, and follow positive data in April from a phase three trial examining the experimental pill in diabetes patients. They bring Eli Lilly's pill, orforglipron, one step closer to becoming the first new, needle-free alternative in the booming market for weight loss and diabetes drugs called GLP-1s.
Eli Lilly expects to submit the data to regulators by the end of the year, with plans to launch the pill in 2026, Ken Custer, president of Lilly Cardiometabolic Health, said in an interview.
That launch could fundamentally shift the space, helping more patients access the treatments and alleviating the supply shortfalls of existing injections. The more convenient and easier-to-manufacturer pill could also help Eli Lilly solidify its dominance in the growing segment as other drugmakers, including its main rival Novo Nordisk, race to bring weight loss pills to market.
Custer said there are roughly 8 million patients on injectable obesity and diabetes drugs, but likely around 170 million who could benefit from the medicines.
"In order to meet that demand, we're going to need other options, including oral small molecules like orforglipron, which use different means of production and also don't need as sophisticated of a supply chain to distribute it to patients," he said.
Dr. Amy Sheer, professor of medicine and program director of the Obesity Medicine Fellowship at University of Florida, said she hopes the pill will be less expensive than existing injections, which are costly largely due to the devices they come in. She said lower prices could help eliminate barriers to access for patients, potentially making insurers more willing to cover the drug.
Many insurers still don't cover GLP-1s for obesity. Wegovy and other drugs have list prices of roughly $1,000 before insurance.
The highest dose of Eli Lilly's pill helped more than 59% of patients lose at least 10% of their body weight and more than 39% of patients lose at least 15% of their weight, according to the trial results.
Almandoz said the proportion of people who achieved "greater magnitudes" of weight loss was "very impressive for an oral agent," adding that many people "often overlook the proportion of people achieving these high weight loss categories" and typically focus closely on the average weight loss
Orforglipron also helped lessen cardiovascular risk factors.
But data on how well some patients tolerated the pill in the trial came under some analysts' estimates.
About 10.3% of patients who took the highest dose of the pill — 36 milligrams — discontinued treatment due to side effects, compared with around 2.6% of those who took placebo. Those side effects were mainly gastrointestinal, such as nausea and vomiting, and mild to moderate in severity. An estimated 24% of those who took the highest dose experienced vomiting, while 33.7% and 23.1% had nausea and diarrhea, respectively.
Ahead of the data, BMO Capital Markets analyst Evan Seigerman said he expected less than 10% of patients on the highest dose of the pill to discontinue treatment due to side effects and lower rates of vomiting, nausea and diarrhea.
More patients stopped taking the pill due to side effects compared with existing GLP-1s on the market, said Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women's Hospital. The discontinuation rates due to side effects in late-stage trials on Wegovy and Eli Lilly's weekly obesity injection Zepbound are around 7% or less.
She noted that almost a quarter of patients on the highest dose of the pill discontinued treatment for any reason, cautioning that the enthusiasm for orforglipron should be tempered "because we get all this excitement, and then the pill comes out, and then nobody can take it."
It's unclear why, apart from side effects, those patients discontinued the pill.
But University of Florida's Sheer said she doesn't believe the discontinuation rates or side effects will be a deciding factor for physicians when prescribing the pill.
She believes an oral option could actually make more physicians more comfortable prescribing a GLP-1 to patients. Some physicians are currently hesitant to prescribe injections because they "may not know how to tell patients how to use them," Sheer added.
Almandoz said prescribing decisions are going to depend on the patient's specific needs and preferences, as well as access and affordability. An injectable GLP-1 may be the preferred option for patients whose priority is a greater level of weight loss or those who have significant cardiometabolic complications, or health issues that arise from cardiovascular diseases and metabolic disorders.
But an oral GLP-1 could be the best fit for those who "prioritize simplicity or convenience or have these logistical challenges with injections," he said.
The detailed results from the trial will be presented in September at a European medical meeting and published in a peer-reviewed journal. More phase three trial results on the pill will be shared later this year, including from a study on adults who have obesity or are overweight and have Type 2 diabetes.
Wegovy, Eli Lilly's pill, orforglipron and Novo Nordisk's diabetes pill Rybelsus all work by targeting a gut hormone called GLP-1 to promote weight loss and regulate blood sugar. But unlike those other medications, Eli Lilly's pill is not a peptide medication. That means it is absorbed more easily in the body and doesn't require dietary restrictions like Rybelsus does.
Eli Lilly is currently about three years ahead of other drugmakers developing pills, including Pfizer, AstraZeneca, Roche, Structure Therapeutics and Viking Therapeutics, Guggenheim analyst Seamus Fernandez previously CNBC.
Some analysts expect the market for GLP-1s to be worth more than $150 billion annually by the early 2030s. Oral GLP-1s could grow to be worth $50 billion of that total, Fernandez said.