Eli Lilly’s shares shot up 11% pre-market on Thursday after orforglipron became the first small-molecule GLP-1 drug to ace a late-stage study in type 2 diabetes, eliciting significant reductions in body weight and improvements in glucose control.
Eli Lilly’s oral GLP-1 receptor agonist orforglipron can significantly lower blood sugar levels in patients with type 2 diabetes, according to preliminary Phase III data released Thursday. The Big Pharma’s stock price rose 11% on the news, while its main competitor in the GLP-1 space, Novo Nordisk, dropped 6%.
“Has the tortoise caught the hare?” analysts at BMO Capital Markets mused in a note to investors. The group called Thursday’s findings a “positive readout” for orforglipron, adding that “Lilly achieves goal of reaching injectable like efficacy from oral orforglipron.”
In the Phase III ACHIEVE-1 trial, once-daily 36-mg orforglipron lowered average blood glucose levels (A1C) by 1.5% from baseline at 40 weeks, according to Lilly’s Thursday release. Placebo comparators, on the other hand, saw only a 0.1% decrease in A1C over this time period. Orforglipron also hit key secondary endpoints, cutting body weight by 7.9% over 40 weeks versus 1.6% in placebo.
As for safety, orforglipron’s side effect profile was consistent with that of the GLP-1 class. Adverse events were mostly gastrointestinal in nature and were largely mild or moderate in severity. At the 36-mg dose level, 8% of treated patients dropped out due to side effects, as compared with 1% in the placebo arm. There were no liver safety signals detected.
BMO noted that orforglipron’s safety profile “looks clean,” though there remains “some concern” of higher rates of nausea and vomiting. Overall, however, the readout from ACHIEVE-1 “firmly validate the tolerable profile of orforglipron.”
Lilly plans to submit approval applications for orforglipron for weight management by the end of the year, while a regulatory filing in diabetes is slated for 2026.
Like the two GLP-1 leaders—Lilly’s tirzepatide and Novo Nordisk’s semaglutide—orforglipron is an analog of the GLP-1 hormone, and it works by promoting the secretion of insulin from the pancreas in response to a spike in blood sugar. The drug also suppresses appetite and hunger.
Uniquely, however, orforglipron is available orally, which presents several advantages. In addition to allowing patients to avoid regular injections, orforglipron can be taken “any time of the day without restrictions on food or water intake,” according to Lilly’s announcement.
Moreover, as a small-molecule drug, orforglipron is also easier to manufacture. “Unlike the injectables, supply is not likely to be an issue,” analysts at Truist Securities told investors in a Thursday note. Lilly has also long been preparing its manufacturing infrastructure for orforglipron, investing money and expanding its production capacity as early as February 2024.
In its press announcement on Thursday, the pharma noted that if orforglipron wins regulatory approval, it is ready to launch the drug worldwide “without supply constraints.”
“[W]e believe obesity competitor Lilly has made sizable advancements in its commercial and clinical portfolio, causing it to overtake Novo’s early lead,” BMO analysts wrote.
