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SYNERGY-NASH results were presented at the European Association for the Study of the Liver Congress 2024 and simultaneously published in The New England Journal of Medicine
INDIANAPOLIS , June 8, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY ) announced detailed results from SYNERGY-NASH, a phase 2 study of 190 patients, with or without type 2 diabetes, to evaluate the investigational use of tirzepatide in adults with biopsy-proven metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis. The efficacy estimand i showed 51.8%, 62.8% and 73.3% of participants taking 5 mg, 10 mg and 15 mg, respectively, achieved an absence of MASH with no worsening of fibrosis on liver histology compared to 13.2% of participants on placebo at 52 weeks of treatment, meeting the study's primary endpoint. The data were presented at the European Association for the Study of the Liver (EASL) Congress 2024 and simultaneously published in The New England Journal of Medicine (NEJM) .
In a secondary endpoint, the efficacy estimand showed 59.1%, 53.3% and 54.2% of participants taking 5 mg, 10 mg and 15 mg, respectively, achieved a 1-stage or greater fibrosis improvement without worsening of MASH compared to 32.8% of participants on placebo. Evaluation of additional secondary endpoints showed tirzepatide was associated with improvements in body weight, blood markers of liver injury, and biomarkers of liver fat, inflammation and fibrosis. While the phase 2 study was not designed to prove that tirzepatide improves fibrosis, the study results showed the potential for a clinically meaningful treatment effect across all doses.
"MASH is the second most common contributor to liver transplantation in the U.S., highlighting the need for novel therapies 1 ," said Rohit Loomba , MD, MHSc, chief of the division of gastroenterology and hepatology at University of California San Diego School of Medicine. "The study is significant, given the urgent need for treatment options that are capable of slowing the progression of the disease and potentially reducing serious health complications."
Results of the treatment-regimen estimand ii analysis (below) were consistent with those observed with the efficacy estimand:
| Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Placebo | |
| Primary Endpoint | ||||
| MASH resolution without worsening of fibrosis (defined as no increase in fibrosis stage) at week 52 | 43.6 % (p<0.001) | 55.5 % (p<0.001) | 62.4 % (p<0.001) | 9.8 % |
| Secondary Endpoint | ||||
| >1 stage decrease in fibrosis stage without worsening of MASH (defined as no increase in the NAS score iii )* | 54.9 % (p=0.016) | 51.3 % (p=0.039) | 51.0 % (p=0.043) | 29.7 % |
*p values for the secondary endpoint are nominal and not adjusted for multiple comparisons.
The overall safety profile of tirzepatide in SYNERGY-NASH was similar to that observed in the previously reported SURMOUNT and SURPASS trials. The most commonly reported adverse events in SYNERGY-NASH were gastrointestinal-related (nausea, diarrhea, decreased appetite, constipation and weight loss) and generally mild to moderate in severity.
"Lilly is very pleased with the degree of MASH resolution observed in the SYNERGY-NASH study, and we are encouraged by the improvement of fibrosis observed," said Jeff Emmick , MD, PhD, senior vice president, product development, Lilly. "MASH is expected to impact more than 19 million adults in the U.S. by 2039 2 and based on the study results, we believe tirzepatide may have the potential to help people living with this disease."
Lilly is engaged with regulatory authorities on the next steps for tirzepatide for the treatment of MASH.
About SYNERGY-NASH
SYNERGY-NASH was a multicenter, double-blind, randomized, placebo-controlled phase 2 study evaluating the efficacy and safety of tirzepatide at various doses in adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as nonalcoholic steatohepatitis (NASH), with stage 2 or 3 fibrosis. The trial randomized 190 participants to receive tirzepatide 5 mg, 10 mg, 15 mg or placebo, administered subcutaneously once weekly for 52 weeks. The primary endpoint was MASH resolution without worsening of fibrosis at 52 weeks. Secondary endpoints included fibrosis improvement without worsening of MASH.
About tirzepatide
Tirzepatide is a once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist. Tirzepatide is a single molecule that activates the body's receptors for GIP and GLP-1, which are natural incretin hormones. Both GIP and GLP-1 receptors are found in areas of the human brain important for appetite regulation. Tirzepatide has been shown to decrease food intake and modulate fat utilization. Tirzepatide is being studied as a potential treatment for people with obesity and/or overweight with heart failure with preserved ejection fraction (HFpEF), obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatohepatitis (MASH). Studies of tirzepatide in chronic kidney disease (CKD) and in morbidity/mortality in obesity (MMO) are also ongoing.
Tirzepatide was approved by the FDA as Mounjaro ® for adults with type 2 diabetes to improve glycemic control on May 13, 2022, and as Zepbound ® for adults with obesity (a BMI of 30 kg/m 2 or greater) or those who are overweight (a BMI of 27 kg/m 2 or greater) who also have a weight-related comorbid condition on November 8, 2023 . Both Mounjaro and Zepbound should be used as an adjunct to diet and exercise.
INDICATION AND SAFETY SUMMARY WITH WARNINGS
Zepbound™ (ZEHP-bownd) is an injectable prescription medicine that may help adults with obesity, or with excess weight (overweight) who also have weight-related medical problems, lose weight and keep it off. It should be used with a reduced-calorie diet and increased physical activity.
Warnings - Zepbound may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider.
Zepbound may cause serious side effects, including:
Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Zepbound. Tell your healthcare provider if you have stomach problems that are severe or will not go away.
Kidney problems (kidney failure) . Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration.
Gallbladder problems. Gallbladder problems have happened in some people who use Zepbound. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), or clay-colored stools.
Inflammation of the pancreas (pancreatitis). Stop using Zepbound and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
Serious allergic reactions. Stop using Zepbound and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, or very rapid heartbeat.
Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Zepbound with medicines that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, mood changes, hunger, weakness or feeling jittery.
Changes in vision in patients with type 2 diabetes. Tell your healthcare provider if you have changes in vision during treatment with Zepbound.
Depression or thoughts of suicide. You should pay attention to changes in your mood, behaviors, feelings or thoughts. Call your healthcare provider right away if you have any mental changes that are new, worse, or worry you.
Common side effects
The most common side effects of Zepbound include nausea, diarrhea, vomiting, constipation, stomach (abdominal) pain, indigestion, injection site reactions, feeling tired, allergic reactions, belching, hair loss, and heartburn. These are not all the possible side effects of Zepbound. Talk to your healthcare provider about any side effect that bothers you or doesn't go away.
Tell your healthcare provider if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch .
Before using Zepbound
Review these questions with your healthcare provider:
❑ Do you have other medical conditions, including problems with your pancreas or kidneys, or severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems digesting food?
❑ Do you take diabetes medicines, such as insulin or sulfonylureas?
❑ Do you have a history of diabetic retinopathy?
❑ Do you take any other prescription medicines or over-the-counter drugs, vitamins, or herbal supplements?
❑ Are you pregnant, plan to become pregnant, breastfeeding, or plan to breastfeed? Zepbound may harm your unborn baby. Tell your healthcare provider if you become pregnant while using Zepbound. It is not known if Zepbound passes into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using Zepbound.
Zepbound is a prescription medicine. For more information, call 1-800-LillyRx (1-800-545-5979) or go to www.zepbound.lilly.com .
This summary provides basic information about Zepbound 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 Zepbound and how to take it. Your healthcare provider is the best person to help you decide if Zepbound is right for you.
ZP CON CBS 08NOV2023
Zepbound™ and its delivery device base are trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
INDICATION AND SAFETY SUMMARY WITH WARNINGS
Mounjaro® (mown-JAHR-OH) is an injectable medicine for adults with type 2 diabetes used along with diet and exercise to improve blood sugar (glucose).
Warnings - Mounjaro may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider.
Mounjaro may cause serious side effects, including:
Inflammation of the pancreas (pancreatitis). Stop using Mounjaro and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Mounjaro with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, or mood changes, hunger, weakness and feeling jittery.
Serious allergic reactions. Stop using Mounjaro and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, and very rapid heartbeat.
Kidney problems (kidney failure) . In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems to get worse. It is important for you to drink fluids to help reduce your chance of dehydration.
Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Mounjaro. Tell your healthcare provider if you have stomach problems that are severe or will not go away.
Changes in vision. Tell your healthcare provider if you have changes in vision during treatment with Mounjaro.
Gallbladder problems. Gallbladder problems have happened in some people who use Mounjaro. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), and clay-colored stools.
Common side effects
The most common side effects of Mounjaro include nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion, and stomach (abdominal) pain. These are not all the possible side effects of Mounjaro. Talk to your healthcare provider about any side effect that bothers you or doesn't go away.
Tell your healthcare provider if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch .
Before using Mounjaro
Review these questions with your healthcare provider:
❑ Do you have other medical conditions, including problems with your pancreas or kidneys, or severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems digesting food?
❑ Do you take other diabetes medicines, such as insulin or sulfonylureas?
❑ Do you have a history of diabetic retinopathy?
❑ Are you pregnant, plan to become pregnant, breastfeeding, or plan to breastfeed? It is not known if Mounjaro will harm your unborn baby or pass into your breast milk.
❑ Do you take any other prescription medicines or over-the-counter drugs, vitamins, or herbal supplements?
Mounjaro is a prescription medicine. For more information, call 1-833-807-MJRO (833-807-6576) or go to www.mounjaro.com .
This summary provides basic information about Mounjaro 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 Mounjaro and how to take it. Your healthcare provider is the best person to help you decide if Mounjaro is right for you.
TR CON CBS 14SEP2022
Mounjaro ® and its delivery device base are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
i The efficacy estimand represents efficacy prior to study treatment discontinuation. ii The treatment-regimen estimand represents the efficacy for randomized participants regardless of treatment discontinuation. iii The NAFLD Activity Score (NAS) is a histological score that assesses the severity of disease activity for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD).
Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about tirzepatide as a potential treatment for people with metabolic dysfunction-associated steatohepatitis (MASH) and the timeline for future readouts, presentations, and other milestones relating to tirzepatide and its clinical trials, and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, that tirzepatide will receive regulatory approval and prove to be a safe and effective treatment for MASH, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
Refer to: Brooke Frost; [email protected] , 317-432-9145 (media) Joe Fletcher; [email protected] , 317-296-2884 (investors)
SOURCE Eli Lilly and Company