*At 36 weeks, the TOGETHER-PsA study met its primary endpoint of 50% improvement in psoriatic arthritis (PsA) activity based on ACR50 in addition to ≥10% weight reduction with concomitant Taltz and Zepbound compared to Taltz monotherapy *

*In a key secondary endpoint, use of Taltz and Zepbound delivered a 64% relative increase in the proportion of patients achieving ACR50 compared to Taltz alone (*33.5% of patients vs. 20.4%, p<.05)

Taltz is now the first and only biologic for PsA with data supporting a potential comprehensive treatment approach alongside an incretin therapy for patients who also have obesity (BMI ≥30 kg/m²) or overweight (BMI 27-29.9 kg/m²) with at least one weight-related condition

, /PRNewswire/ – Eli Lilly and Company (NYSE: LLY) today announced positive topline results from the novel TOGETHER-PsA open-label Phase 3b trial evaluating the concomitant use of Taltz (ixekizumab) and Zepbound (tirzepatide) compared to Taltz alone in adults with active psoriatic arthritis (PsA) and obesity or overweight with at least one weight-related condition. At 36 weeks, treatment with concomitant Taltz and Zepbound met the primary and all key secondary endpoints for superiority to Taltz monotherapy. TOGETHER-PsA is the first controlled study to evaluate an incretin therapy used with a PsA biologic. An estimated 65% of adults with PsA in the U.S. also have obesity (BMI ≥30 kg/m²) or overweight (BMI 27-29.9 kg/m²) with at least one additional weight-related comorbidity,1 highlighting a need for integrated treatment approaches that address the full burden of their diseases.

In the study, 31.7% of patients in the Taltz plus Zepbound treatment arm achieved a 50% improvement in PsA activity, based on American College of Rheumatology 50 (ACR50), and weight reduction of at least 10%, compared to 0.8% of patients on Taltz monotherapy, meeting the primary endpoint (p<.001). In a key secondary endpoint, Taltz plus Zepbound delivered a 64% relative increase over Taltz monotherapy in the proportion of patients who achieved ACR50 (33.5% of patients vs. 20.4%, respectively, p<.05), demonstrating that treatment of obesity or overweight with Zepbound reduced the burden of PsA.2,3 The study population included patients with a high disease burden at baseline and an average BMI of 37.6 kg/m2 across both arms. Patients had high disease activity and meaningful functional impairment.4 More than 60% had prior experience with one or more advanced therapies, reflecting a difficult-to-treat patient population.

"TOGETHER-PsA represents a pioneering first step leveraging Lilly’s leadership in incretin science to deliver a major advance in disease outcomes for people living with the cumulative burden of psoriatic arthritis and obesity or overweight," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. "This is the first controlled pharmacologic study to demonstrate that treatment of obesity improved PsA disease measures, and we are particularly impressed with the findings showing significant improvement in PsA disease activity with Zepbound used alongside Taltz, an already rapid-acting and durable PsA treatment. These results demonstrate how an integrated treatment approach has the potential to improve the standard of care in a compelling and comprehensive way."

Adverse events in participants treated with concomitant administration of Taltz and Zepbound were generally mild to moderate, and the types of adverse events were consistent with the known safety profile of each medicine. The most common adverse events occurring in ≥5% of participants were nausea, diarrhea, constipation and injection site reactions in the concomitant treatment arm, and injection site reactions and upper respiratory tract infections in the Taltz monotherapy arm.

Taltz is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. Zepbound is the only FDA-approved dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist obesity management medication.

"While treatment guidelines for psoriatic arthritis recommend management of obesity, the reality is these two chronic diseases are often addressed separately and moving the needle in psoriatic arthritis has remained challenging," said Joseph F. Merola, M.D., Professor and Chair, Department of Dermatology and Professor of Internal Medicine in the Division of Rheumatic Diseases, UT Southwestern Medical Center. "The observed benefit with treatment using Taltz and Zepbound appears to meaningfully impact psoriatic disease activity, indicating that for many patients, PsA is an obesity-related condition. This integrated therapy approach represents a potential paradigm shift and could lead to better outcomes for those living with both diseases."

Detailed 36-week results from the TOGETHER-PsA trial will be presented at an upcoming medical meeting and discussed with regulators. Topline results from the ongoing TOGETHER-PsO trial, investigating the efficacy and safety of treating adults who have moderate-to-severe plaque psoriasis and obesity or overweight with concomitant Taltz and Zepbound compared to Taltz monotherapy, are also expected in the first half of 2026.

**About the TOGETHER-PsA Trial **TOGETHER-PsA (NCT06588296) is a 52-week Phase 3b, randomized, multicenter, assessor-blinded, open-label study assessing the efficacy and safety of concomitant administration of Taltz and Zepbound compared with Taltz alone in adult participants with active psoriatic arthritis and obesity or overweight. A total of 271 participants were randomized 1:1 to receive either Taltz alone or concomitantly with Zepbound, both administered subcutaneously. Patients in both arms received counseling on a reduced-calorie diet and increased physical activity. The primary objective of the study is to assess the proportion of participants achieving both an ACR50 response and ≥10% weight reduction at Week 36. Participants must have a BMI ≥30 kg/m², or ≥27 to <30 kg/m² with at least one weight-related comorbidity.

**About Taltz (ixekizumab)5 **Taltz is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Taltz inhibits the release of pro-inflammatory cytokines and chemokines. Taltz is approved to treat adults with active psoriatic arthritis. Additionally, Taltz is approved for adults and children 6 years and older with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, adults with active ankylosing spondylitis, and adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation.

About Zepbound (tirzepatide) injection6 Zepbound is a GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist obesity medication. Zepbound lowers body weight by decreasing calorie intake and appetite. Zepbound is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction in adults with obesity, or adults with overweight in the presence of at least one weight-related comorbid condition. Additionally, Zepbound is FDA-approved to treat adults with moderate-to-severe obstructive sleep apnea and obesity in combination with a reduced-calorie diet and increased physical activity. Zepbound contains tirzepatide and should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines. It is not known if Zepbound is safe and effective for use in children.

Endnotes and References

1

Estimated from a large real-world population of care-seeking adults in the US in 2024, Truveta (data on file). Comorbidities include atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes mellitus (T2DM), dyslipidemia, hypertension, obstructive sleep apnea (OSA).

2

Hypothetical efficacy estimand in the modified intent-to-treat (mITT) population is used. The hypothetical efficacy estimand represents efficacy in all mITT participants who remained on study intervention without initiating prohibited medication.

3

ACR50 is a composite measure requiring at least a 50% improvement in the number of tender joints (TJC) and swollen joints (SJC), plus at least a 50% improvement in three of the five other core disease activity measures (patient pain assessment, patient global assessment of disease activity, physician global assessment of disease activity, patient assessment of physical function by health assessment questionnaire, and an acute phase reactant as measured by High-Sensitivity C-Reactive Protein [hsCRP]).

4

High disease activity was defined as a mean Disease Activity Index for Psoriatic Arthritis (DAPSA) score of 58.65 at baseline. Functional impairment was defined as a mean Health Assessment Questionnaire – Disability Index (HAQ-DI) score of 1.3 at baseline.

5

Taltz. Prescribing Information. Lilly USA, LLC.

6

Zepbound. Prescribing Information. Lilly USA, LLC.

**TALTZ INDICATIONS AND SAFETY SUMMARY **Taltz® (tȯl-ts) is an injectable medicine used to treat:

• People 6 years of age and older with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or treatment using ultraviolet or UV light (phototherapy).
• Adults with active psoriatic arthritis.
• Adults with active ankylosing spondylitis.
• Adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation.

It is not known if Taltz is safe and effective in children for conditions other than plaque psoriasis or in children under 6 years of age.

Warnings - Taltz affects the immune system. It may increase your risk of infections, some people have had serious infections, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have been hospitalized from these infections. Do not use Taltz if you have any symptoms of infection, unless your doctor tells you to. If you have a symptom after starting Taltz, call your doctor right away.

Your doctor should check you for TB before you start Taltz, and watch you closely for signs of TB during and after treatment with Taltz. If you have TB, or had it in the past, your doctor may treat you for it before you start Taltz.

Do not use Taltz if you have had a serious allergic reaction to ixekizumab or any other ingredient in Taltz, such as: swelling of your eyelids, lips, mouth, tongue or throat, trouble breathing, feeling faint, throat or chest tightness, or skin rash. Get emergency help right away if you have any of these reactions. See the Medication Guide that comes with Taltz for a list of ingredients.

Severe skin reactions that look like eczema can happen during treatment with Taltz from days to months after your first dose and can sometimes lead to hospitalization. Your doctor may temporarily stop treatment with Taltz if you develop severe skin reactions. Tell your doctor if you have any of the following: redness or rash, itching, patches, your skin is dry or feels like leather, blisters or abrasions that ooze or become crusty, small bumps or plaques with scale or crusting.

Crohn’s disease or ulcerative colitis (inflammatory bowel disease) can start or get worse with Taltz use. Tell your doctor if you have any of these symptoms or if they get worse: stomach pain, diarrhea, and weight loss.

You should not get live vaccines while taking Taltz. You should get the vaccines you need before you start Taltz.

Common side effects The most common side effects of Taltz include:

• Injection site reactions
• Nausea
• Upper respiratory infections
• Fungal skin infections

Tell your doctor if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.

**Before using **Before you use Taltz, review these questions with your doctor:

• Are you being treated for an infection?
• Do you have an infection that does not go away or keeps coming back?
• Do you have TB or have you been in close contact with someone with TB?
• Do you have possible symptoms of an infection such as fever, cough, sores, diarrhea, or other symptoms? Ask your doctor about other possible symptoms.
• Do you have Crohn’s disease or ulcerative colitis?

Tell your doctor if:

• You need any vaccines or have had one recently.
• You take prescription or over-the-counter medicines, vitamins, or herbal supplements.
• You are pregnant or planning to become pregnant. It is not known if Taltz can harm an unborn baby.
• Pregnancy Exposure Registry: There is a pregnancy registry to collect information about women who are exposed to Taltz during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. If you become pregnant while taking Taltz, you are encouraged to enroll in the pregnancy registry by calling 1-800-284-1695 or by visiting online at http://www.pregnancyregistry.lilly.com.
• You are breastfeeding or planning to breastfeed. It is not known if Taltz passes into breastmilk.

**How to take **See the instructions for use that come with Taltz. There you will find information about how to store, prepare, and inject Taltz. Adults may self-inject after receiving training from a healthcare provider.

For children 6 to 17 years of age:

• If your child’s healthcare provider decides that you may give Taltz injections at home, you should receive training on the right way to prepare and inject Taltz. Do not try to give Taltz to your child until you have been shown how to inject Taltz. Children should not inject themselves with Taltz. You or an adult caregiver should prepare and give Taltz injections to your child.

**Learn more **Taltz is a prescription medicine available as a 80 mg/mL, 40 mg/0.5mL, 20 mg/0.25mL injection. For more information, call 1-800-545-5979 or go to taltz.lilly.com.

This summary provides basic information about Taltz 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 doctor. Be sure to talk to your doctor or other healthcare provider about Taltz and how to take it. Your doctor is the best person to help you decide if Taltz is right for you.

IX CON BS 20AUG2024

**ZEPBOUND INDICATIONS AND SAFETY SUMMARY WITH WARNINGS **Zepbound® (ZEHP-bownd) is an injectable prescription medicine that may help adults with:

• obesity, or some adults with overweight who also have weight-related medical problems to lose excess body weight and keep the weight off.
• moderate-to-severe obstructive sleep apnea (OSA) and obesity to improve their OSA.

It should be used with a reduced-calorie diet and increased physical activity.

Zepbound contains tirzepatide and should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines. It is not known if Zepbound is safe and effective for use in children.

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.

• Do not use Zepbound if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC).
• Do not use Zepbound if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• Do not use Zepbound if you have had a serious allergic reaction to tirzepatide or any of the ingredients in Zepbound.

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.

Dehydration leading to kidney problems. 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*.*

Food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). Zepbound may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking Zepbound before you are scheduled to have surgery or other procedures.

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 doctor if you have any side effects. **You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch. **

**Before using Zepbound **

• **Your healthcare provider should show you how to use Zepbound before you use it for the first time. **
• **Talk to your healthcare provider about low blood sugar and how to manage it. Tell your healthcare provider if you are taking medicines to treat diabetes including an insulin or sulfonylurea. **
• **If you take birth control pills by mouth, talk to your healthcare provider before you use Zepbound. Birth control pills may not work as well while using Zepbound. Your healthcare provider may recommend another type of birth control for 4 weeks after you start Zepbound and for 4 weeks after each increase in your dose of Zepbound. **

**Review these questions with your healthcare provider: **

• Do you have other medical conditions, including problems with your pancreas, 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 scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation)?
• 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. Zepbound may pass into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using Zepbound.
• Pregnancy Exposure Registry: There will be a pregnancy exposure registry for women who have taken Zepbound during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry, or you may contact Lilly at 1-800-LillyRx (1-800-545-5979).

**How to take **

• Read the Instructions for Use that come with Zepbound.
• Use Zepbound exactly as your healthcare provider says.
• Use Zepbound with a reduced-calorie diet and increased physical activity.
• Inject Zepbound under the skin (subcutaneously) of your stomach (abdomen), thigh, or have another person inject in the back of the upper arm. Do not inject ZEPBOUND into a muscle (intramuscularly) or vein (intravenously).
• Use Zepbound 1 time each week, at any time of the day.
• Change (rotate) your injection site with each weekly injection. Do not use the same site for each injection.
• If you take too much Zepbound, call your healthcare provider, call the Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.

Zepbound injection is approved as a 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg per 0.5 mL in single-dose pen or single-dose vial.

Learn more 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 BS 25SEP2025

About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer’s disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY

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**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 Taltz (ixekizumab) as a treatment for active psoriatic arthritis and moderate to severe plaque psoriasis and Zepbound (tirzepatide) as a treatment for adults with obesity or overweight, potential integrated treatment strategies for patients with psoriatic arthritis and obesity, and the timeline for future readouts, 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 future study results will be consistent with the results to date, or that Lilly will execute its strategies as planned. 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.

SOURCE Eli Lilly and Company