After Eli Lilly’s phase 3 data drop for its oral GLP-1 asset orforglipron earlier this month, the Indianapolis drugmaker has unveiled the second half of the data package that will support the med’s chances of securing a green light in obesity.
Tuesday, Lilly reported that all three doses of orforglipron helped its late-stage Attain-2 trial meet its primary endpoint and all key secondary endpoints. The drug helped patients achieve up to an average of 23 pounds in weight loss as well as a reduction in average blood sugar levels and cardiometabolic risk factors by the trial’s 72-week mark.
Attain-2 assessed the safety and efficacy of orforglipron in patients who are overweight or with obesity and also have Type 2 diabetes.
A once-daily dose of 36 mg orforglipron taken without food or water restrictions helped lower patients’ weight by an average of 10.5%, or 22.9 pounds, versus a 2.2% average (5.1 pound) reduction among those on placebo.
By comparison, the 12-mg and 6-mg orforglipron doses triggered a mean weight reduction of 7.8% (17.4 pounds) and 5.5% (12.1 pounds), respectively.
Breaking down the study’s secondary metrics, a little more than 50% of patients on the highest dose of Lilly’s drug lost at least 10% of their body weight versus 7% of patients on placebo. Meanwhile, 35.5% of patients on 12 mg orforglipron and 23.9% of those on the 6-mg dose achieved the same.
Roughly 28% of patients on the highest orforglipron dose lost at least 15% of their body weight, which is closer to the rate seen among injectable GLP-1s like Lilly’s own Zepbound.
Meanwhile, Lilly’s drug also helped patients lower their average blood sugar levels over time, with the 36-mg dose triggering an average A1C reduction of 1.8% from a mean baseline of 8.1% after 72 weeks. Orforglipron also “showed clinically meaningful benefits” across cardiovascular risk factors like non-HDL cholesterol, systolic blood pressure and triglycerides, according to Lilly.
The drug’s safety was on par with its known profile from other clinical trials. The most common orforglipron side effects in the study were gastrointestinal and were generally mild to moderate in severity, Lilly said.
The company plans to share full results from the study at a future medical conference and in a peer-reviewed journal.
The data reveal comes a little less than three weeks after Lilly shared results from Attain-1, which looked at the same orforglipron doses in obese or overweight patients with at least one weight-related comorbidity excluding diabetes. The oral medicine led to an average weight reduction of 12.4%—or 27.3 pounds—at the highest dose. All three doses tested were successful, but, as in Attain-2, the average weight patients lost dropped as the doses descended.
Although Attain-1 hit its clinical goal, Lilly’s share price fell a precipitous 13% on the day of the data release, signaling the lofty expectations investors have for the GLP-1 obesity market. The 12.4% weight loss reported by Lilly is less than Novo Nordisk's CagriSema, an investigational combination of amylin analog cagrilintide and GLP-1 drug semaglutide that was tied to 15.7% weight loss in a phase 3.
After publicly sharing the data from Attain-1, Lilly’s chief scientist Daniel Skovronsky, M.D., Ph.D., said, “[t]his is as good as it gets for GLP-1 monotherapy here in the once-a-day small molecule [space]," on a recent earnings call.
With the Attain-2 data in hand, Lilly now has the full clinical data package it needs to kick off approval submissions with global regulators. Earlier this month, during communications on the Attain-1 data, Lilly said it aimed to submit its regulatory applications for orforglipron before the end of the year.
“The ATTAIN-2 results reinforce the potential for orforglipron, as a once-daily oral, to deliver meaningful weight loss and A1C reduction, consistent with similar landmark trials for injectable GLP-1s,” Kenneth Custer, Ph.D., executive vice president and president of Lilly’s cardiometabolic health unit, said in a statement. “With these positive data in hand, we are moving with urgency toward global regulatory submissions to potentially meet the needs of patients who are waiting.”
Analysts with Citi viewed the new data favorably, writing in an Aug. 26 note that they believe "orforglipron is poised to be the first commercially successful oral GLP-1," citing its efficacy, clean safety and tolerability profile and lack of food restrictions.
William Blair analysts took it a step further, describing the data "as yet another surprising development" in which orforglipron outperformed expectations. The analysts consider the indication of both overweight/obesity and Type 2 diabetes as more difficult to treat and carrying higher risk, writing that orforglipron has demonstrated the highest competitive advantage in diabetes out of the asset's three phase 3 trials thus far.
Investors appear to agree, with Lilly's stock rising nearly 3%, or by about $20 per share, at market open.
Beyond its potential use as an obesity monotherapy, Lilly is also assessing whether to deploy orforglipron in other related contexts. Part and parcel to that goal, Lilly is trialing the molecule as a potential maintenance therapy to prevent weight regain in patients who’ve had success on injectable obesity drugs like Zepbound.
Editor's note: This story was updated at 9:30 a.m. to include analyst and investor information.