Lilly's phase 2 results published in the New England Journal of Medicine show orforglipron, a once-daily oral nonpeptide GLP-1 receptor agonist, achieved up to 14.7% mean weight reduction at 36 weeks in adults with obesity or overweight
- Category: Small Molecules
- Published on Saturday, 24 June 2023 16:06
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In additional phase 2 data, published in The Lancet, orforglipron achieved mean reduction in A1C up to 2.1% at 26 weeks in adults with type 2 diabetes
Lilly is investigating orforglipron, its first nonpeptide oral GLP-1 receptor agonist, for chronic weight management in the ATTAIN phase 3 clinical program and for type 2 diabetes in the ACHIEVE phase 3 clinical program
INDIANAPOLIS, IN, USA I June 23, 2023 I Eli Lilly and Company (NYSE: LLY) announced today new phase 2 data for orforglipron, its first nonpeptide oral glucagon-like peptide-1 (GLP-1) receptor agonist being studied for chronic weight management in participants with obesity or overweighti. The results were shared during an oral presentation at the American Diabetes Association's® 83rd Scientific Sessions and were simultaneously published in the New England Journal of Medicine. Orforglipron met both primary and secondary endpoints for the efficacy estimandii and demonstrated clinically significant weight reductions in adults with obesity or overweight, with at least one weight-related comorbidity (not including type 2 diabetes).
At the 26-week primary endpoint, orforglipron (12 mg, 24 mg, 36 mg or 45 mg) showed statistically significant dose-dependent body weight reductions for all doses ranging from 8.6% (19.8 lb. or 9.0 kg) to 12.6% (29.3 lb. or 13.3 kg) compared to 2.0% (4.6 lb. or 2.1 kg) for placebo. For those taking orforglipron, body weight continued to decrease at 36 weeks where all doses achieved body weight reductions ranging from 9.4% (21.6 lb. or 9.8 kg) to 14.7% (34.0 lb. or 15.4 kg) compared to 2.3% (5.3 lb. or 2.4 kg) for placebo. The mean baseline body weight of participants was 240 lb. (109 kg).
The safety profile of orforglipron was similar to other incretin-based therapies. Gastrointestinal side effects were the most commonly reported adverse events, were generally mild-to-moderate in severity, and usually occurred during the dose escalation period.
"We recognize that obesity is a global epidemic and there is a need for a variety of effective medications and administration routes," said Dr. Sean Wharton, Director at Wharton Medical Clinic. "We are working to address these needs by researching different options, including a daily oral pill called orforglipron. In a phase 2 study, orforglipron demonstrated an average of up to 14.7% weight reduction. These exciting results indicate that orforglipron may be an effective, once-daily oral that can be taken without food or water restrictions."
All four tested doses of orforglipron achieved all key secondary endpoints at 36 weeks of treatment for the efficacy estimand, including participants achieving:
- Body weight reductions of ≥5%: 72% (12 mg), 90% (24 mg), 92% (36 mg) and 90% (45 mg) compared to 24% with placebo
- Body weight reductions of ≥10%: 47% (12 mg), 62% (24 mg), 75% (36 mg) and 69% (45 mg) compared to 9% with placebo
- BMI reduction from baseline: 3.4 kg/m2 (12 mg), 4.7 kg/m2 (24 mg), 5.0 kg/m2 (36 mg) and 5.5 kg/m2 (45 mg) compared to 0.9 kg/m2 with placebo
- Waist circumference reduction from baseline: 9.6 cm (12 mg), 11.2 cm (24 mg), 10.6 cm (36 mg) and 13.6 cm (45 mg) compared to 4 cm with placebo
An additional phase 2 study evaluated orforglipron for the treatment of type 2 diabetes compared to placebo and dulaglutide. Data were presented at the American Diabetes Association's 83rd Scientific Sessions and simultaneously published in The Lancet. The study met its primary and secondary endpoints, demonstrating orforglipron achieved meaningful reductions in A1C and body weight at 26 weeks with an adverse events profile consistent with other GLP-1 receptor agonists. In that study, for the efficacy estimand, mean reduction in A1C (from a mean baseline of 8.1%) with orforglipron at 26 weeks was up to 2.1% compared to 0.4% with placebo and 1.1% with dulaglutide. Orforglipron (3 mg, 12 mg, 24 mg, 36 mg or 45 mg) also demonstrated weight reductions up to 10.1 kg (or 22.3 lb.) in adults with type 2 diabetes (from a mean baseline of 100.3 kg or 221.1 lb.) compared to 2.2 kg (or 4.9 lb.) with placebo and 3.9 kg (or 8.6 lb.) for dulaglutide. With orforglipron, 65% to 96% of participants achieved an A1C of less than 7.0% at 26 weeks versus 64% in the dulaglutide group and 24% in the placebo group. An A1C of less than 5.7% was demonstrated with orforglipron doses greater than 3 mg in 18% to 34% of participants.
"People living with chronic diseases such as type 2 diabetes and obesity deserve options – including oral treatments – to meet their treatment needs. In two phase 2 studies, orforglipron demonstrated the ability to lower weight and A1C in both patient populations," said Jeff Emmick, MD, Ph.D., senior vice president, product development, Lilly. "These study results support the continued development of orforglipron in phase 3. We look forward to those results and the continued development of our pipeline assets that explore novel treatments for type 2 diabetes and obesity."
Lilly has initiated phase 3 development programs to further study the efficacy and safety of orforglipron for the treatment of obesity and overweight (ATTAIN trials) and type 2 diabetes (ACHIEVE trials).
About The Obesity Study (NCT05051579)
The phase 2 study was a 36-week, multicenter, randomized, double-blind, parallel, placebo-controlled study evaluating the efficacy and safety of orforglipron (12 mg, 24 mg, 36 mg or 45 mg) compared to placebo in people with obesity or overweight with at least one weight-related comorbidity, not including type 2 diabetes. Orforglipron or placebo was administered daily by an oral capsule in the morning without food or water restrictions. All participants were provided healthy eating and exercise education by study personnel throughout the trial.
The primary endpoint was percent change in weight from baseline at 26 weeks, and secondary endpoints included change from baseline at 36 weeks in weight, waist circumference and BMI, and participants achieving weight reductions of ≥5% and ≥10%.
About The Type 2 Diabetes Study (NCT05048719)
The phase 2 study was a 26-week, double-blind, randomised, multicenter study evaluating the efficacy and safety of orforglipron (3 mg, 12 mg, 24 mg, 36 mg or 45 mg) compared to placebo and dulaglutide in adults with type 2 diabetes.
The primary endpoint was mean change in A1C from baseline with orforglipron compared to placebo at 26 weeks.
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Orforglipron was discovered by Chugai Pharmaceutical Co., Ltd. and licensed to Lilly in 2018. Chugai and Lilly published the preclinical pharmacology data of this molecule together (PNAS 2020).
Trulicity (dulaglutide) Indications
Trulicity® (Trῡ-li-si-tee) is for adults and children 10 years of age and older with type 2 diabetes used along with diet and exercise to improve blood sugar (glucose). Trulicity is also used in adults with type 2 diabetes to reduce the risk of major cardiovascular events (problems having to do with the heart and blood vessels) such as death, heart attack, or stroke in people who have heart disease or multiple cardiovascular risk factors.
- It is not known if TRULICITY can be used in people who have had inflammation of the pancreas (pancreatitis). TRULICITY is not for use in people with type 1 diabetes and is not recommended for use in people with severe stomach or intestinal problems. It is not known if TRULICITY is safe and effective in children under 10 years of age.
- Trulicity is given through an injection (needle). You take it once a week by injecting it under the skin of your stomach, thigh, or upper arm.
Trulicity is a prescription medicine. For more information, call 1-844-TRU-INFO (1-844-878-4636) or go to www.TRULICITY.com.
This summary provides basic information about Trulicity but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your healthcare provider. Be sure to talk to your healthcare provider about Trulicity and how to take it. Your healthcare provider is the best person to help you decide if Trulicity is right for you.
DG CON HL BS 17NOV2022
Trulicity® and its delivery device base are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
i For the obesity study (NCT05051579), trial participants needed to have a Body Mass Index (BMI) of ≥27 kg/m2 to be classified as overweight.
ii The efficacy estimand is the primary estimand which evaluates the treatment effect of all randomized eligible participants while adhering to treatment.
SOURCE: Eli Lilly