Second Phase 3 Induction Study Confirms Upadacitinib (RINVOQ™) Improved Clinical, Endoscopic and Histologic Outcomes in Ulcerative Colitis Patients

- 33 percent of patients achieved the primary endpoint of clinical remission (per Adapted Mayo Score) compared to 4 percent of patients treated with placebo at week 8 (p<0.001)[1]

- All ranked secondary endpoints were met[1]

- These results reaffirm findings from the first Phase 3 induction study, U-ACHIEVE[1,2]

- Safety results were consistent with the previous Phase 3 induction study and the known profile of upadacitinib, with no new safety risks observed[1-6]

- Upadacitinib, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is being studied as an oral therapy for moderate to severe ulcerative colitis and several other immune-mediated diseases[1,7-14]

News provided by

AbbVie

Feb 22, 2021, 08:45 ET

NORTH CHICAGO, Ill., Feb. 22, 2021 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that upadacitinib (45 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) and all ranked secondary endpoints in the Phase 3 induction study, U-ACCOMPLISH.¹ In the study, 33 percent of patients receiving upadacitinib achieved clinical remission (per Adapted Mayo Score) at week 8 compared to 4 percent of patients receiving placebo (p<0.001).¹ U-ACCOMPLISH is the second of two Phase 3 induction studies to evaluate the safety and efficacy of upadacitinib in adults with moderate to severe ulcerative colitis.¹

"We remain steadfast in our pursuit of transforming the treatment landscape for people living with ulcerative colitis," said Tom Hudson, senior vice president of research and development, AbbVie. "These positive results confirm the findings of the previous induction study and underscore the potential impact upadacitinib could have on patients struggling to manage their disease."

In this study, all ranked secondary endpoints were met, including clinical, endoscopic and histologic outcomes.¹ A greater proportion of patients treated with upadacitinib achieved clinical response compared to placebo, with 74 percent of upadacitinib-treated patients experiencing clinical response (per Adapted Mayo Score) at week 8 versus 25 percent of patients receiving placebo (p<0.001).¹ Additionally, 63 percent of patients treated with upadacitinib achieved clinical response (per partial Adapted Mayo Score) at week 2 versus 26 percent of those receiving placebo (p<0.001).¹ At week 8, 44 percent of patients treated with upadacitinib achieved endoscopic improvement versus 8 percent of patients receiving placebo (p<0.001).¹ And significantly more upadacitinib-treated patients achieved histologic-endoscopic mucosal improvement at week 8 compared to patients receiving placebo (37 percent versus 6 percent; p<0.001).¹

"People living with moderate to severe ulcerative colitis continue to suffer from the significant burden of this disease," said Silvio Danese, M.D., lead study investigator and head of the Inflammatory Bowel Diseases Centre at Humanitas Research Hospital, Milan, Italy. "I am very impressed with the consistent results seen in both ulcerative colitis induction studies, suggesting that upadacitinib could be a potential new treatment option for patients."

*U-ACCOMPLISH Efficacy Results at Week 8^,1**
	Upadacitinib 45 mg, once daily (n=341)	Placebo (n=174)
Clinical remission (per Adapted Mayo Score)^a,†	33%	4%
Clinical response (per Adapted Mayo Score)^b,†	74%	25%
Endoscopic improvement^c,†	44%	8%
Histologic-endoscopic mucosal improvement^d,†	37%	6%

*Primary endpoint was clinical remission (per Adapted Mayo Score). Clinical response (per Adapted Mayo Score), endoscopic improvement and histologic-endoscopic mucosal improvement were ranked secondary endpoints. Not all ranked secondary endpoints are shown. All primary and ranked secondary endpoints achieved p-values of <0.001 versus placebo.

^aClinical remission (per Adapted Mayo Score) is defined as stool frequency subscore (SFS) ≤1 and not greater than baseline, rectal bleeding subscore (RBS) of 0 and endoscopic subscore ≤1.

^bClinical response (per Adapted Mayo Score) is defined as a decrease from baseline in the Adapted Mayo score ≥2 points and ≥30 percent from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1.

^cEndoscopic improvement is defined as endoscopic subscore ≤1.

^dHistologic-endoscopic mucosal improvement is defined as endoscopic subscore of 0 or 1 and Geboes score ≤3.1.

^†Evidence of friability during endoscopy in subjects with otherwise "mild" endoscopy activity will confer an endoscopic subscore of 2.

The safety profile of upadacitinib (45 mg) was consistent with the safety findings in the previously reported Phase 3 induction study in ulcerative colitis and safety findings in previous studies across indications, with no new safety risks observed.^1-6 During the 8-week study period, the most common adverse events observed in the upadacitinib group were acne, blood creatine phosphokinase increase and anemia.¹ The increases in blood creatine phosphokinase were non-serious and did not lead to study drug discontinuation.¹Patients with blood creatine phosphokinase increase were usually asymptomatic and no cases of rhabdomyolysis were reported.¹ Serious adverse events occurred in 3.2 percent of patients in the upadacitinib group and 4.5 percent of patients in the placebo group.¹ Similar rates of serious infections (0.6 percent) were observed in the two treatment groups.¹ No deaths, gastrointestinal perforation, malignancy, major cardiovascular or thromboembolic events were reported in the upadacitinib group.¹One case of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and one case of gastrointestinal perforation was reported in the placebo group.¹

Full results from the U-ACCOMPLISH study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal. Top-line results from the Phase 3 portion of the first induction study, U-ACHIEVE, were announced in December 2020 and the maintenance study for both is ongoing. Use of upadacitinib in ulcerative colitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

About Ulcerative Colitis

Ulcerative colitis is a chronic, systemic, inflammatory disease caused by inflammation of the large intestine, which triggers abdominal pain, bloody diarrhea, severe urgency for a bowel movement, weight loss and fatigue.^15-17 The severity of symptoms and uncertainty surrounding flares cause a substantial burden and often disability among those living with the disease.¹⁸

About the U-ACCOMPLISH Study^1,9

U-ACCOMPLISH is a Phase 3 multicenter, randomized, double-blind, placebo-controlled induction study to evaluate the efficacy and safety of upadacitinib 45 mg once daily for induction therapy compared to placebo in subjects with moderate to severe ulcerative colitis. U-ACCOMPLISH is the second of two Phase 3 induction studies.

The primary endpoint is achievement of clinical remission (per Adapted Mayo Score) at week 8. Ranked secondary endpoints included clinical response (decrease from baseline in the Adapted Mayo score ≥2 points and ≥30 percent from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1), endoscopic improvement (endoscopic subscore ≤1) and histologic-endoscopic mucosal improvement (endoscopic subscore of 0 or 1 and Geboes score ≤3.1) at week 8. More information can be found on www.clinicaltrials.gov (NCT03653026).

About the Upadacitinib Ulcerative Colitis Program^9,19,20

The global upadacitinib ulcerative colitis program evaluates more than 1,300 patients with moderately to severely active ulcerative colitis across three pivotal studies. These studies include assessments of efficacy and safety of upadacitinib. Key measures of efficacy include clinical remission (per Adapted Mayo Score), clinical response (per Adapted Mayo Score), endoscopic improvement and endoscopic response. More information on these trials can be found at www.clinicaltrials.gov (NCT03653026, NCT02819635, NCT03006068).

About Upadacitinib (RINVOQ)

Discovered and developed by AbbVie scientists, RINVOQ is an oral, once daily, selective and reversible JAK inhibitor studied in several immune-mediated inflammatory diseases.^1,7-14 It was engineered to have greater inhibitory potency for JAK1 versus JAK2, JAK3 and TYK2.³ In August 2019, RINVOQ received U.S. Food and Drug Administration approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. RINVOQ is also approved by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs); active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs and active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy. The approved dose for RINVOQ in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis is 15 mg. Phase 3 trials of RINVOQ in ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, atopic dermatitis and giant cell arteritis are ongoing.^8-14 Use of RINVOQ in ulcerative colitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Important Safety Information about RINVOQ (upadacitinib)²¹

RINVOQ U.S. Use and Important Safety Information
RINVOQ is a prescription medicine used to treat adults with moderate to severe rheumatoid arthritis in whom methotrexate did not work well or could not be tolerated. It is not known if RINVOQ is safe and effective in children under 18 years of age.

What is the most important information I should know about RINVOQ?
RINVOQ is a medicine that can lower the ability of your immune system to fight infections. You should not start taking RINVOQ if you have any kind of infection unless your healthcare provider (HCP) tells you it is okay.

Serious infections have happened in some people taking RINVOQ, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Your HCP should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You may be at higher risk of developing shingles (herpes zoster).
Lymphoma and other cancers, including skin cancers, can happen in people taking RINVOQ.
Blood clots in the veins of the legs or lungs and arteries are possible in some people taking RINVOQ. This may be life-threatening and cause death.
Tears in the stomach or intestines and changes in certain laboratory tests can happen. Your HCP should do blood tests before you start taking RINVOQ and while you take it. Your HCP may stop your RINVOQ treatment for a period of time if needed because of changes in these blood test results.

What should I tell my HCP BEFORE starting RINVOQ?
Tell your HCP if you:

Are being treated for an infection, have an infection that won't go away or keeps coming back, or have symptoms of an infection such as:

Fever, sweating, or chills
Shortness of breath
Warm, red, or painful skin or sores on your body
Muscle aches
Feeling tired
Blood in phlegm
Diarrhea or stomach pain
Cough
o Weight loss
Burning when urinating or urinating more often than normal

Have TB or have been in close contact with someone with TB.
Have had any type of cancer, hepatitis B or C, shingles (herpes zoster), or blood clots in the veins of your legs or lungs, diverticulitis (inflammation in parts of the large intestine), or ulcers in your stomach or intestines.
Have other medical conditions including liver problems, low blood cell counts, diabetes, chronic lung disease, HIV, or a weak immune system.
Live, have lived, or have traveled to parts of the country that increase your risk of getting certain kinds of fungal infections, such as the Ohio and Mississippi River valleys and the Southwest. If you are unsure if you've been to these areas, ask your HCP.
Have recently received or are scheduled to receive a vaccine. People who take RINVOQ should not receive live vaccines.
Are pregnant or plan to become pregnant. Based on animal studies, RINVOQ may harm your unborn baby. Your HCP will check whether or not you are pregnant before you start RINVOQ. You should use effective birth control (contraception) to avoid becoming pregnant while taking RINVOQ and for at least 4 weeks after your last dose.
Are breastfeeding or plan to breastfeed. RINVOQ may pass into your breast milk. You should not breastfeed while taking RINVOQ and for at least 6 days after your last dose.

Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RINVOQ and other medicines may affect each other, causing side effects.

Especially tell your HCP if you take:

Medicines for fungal or bacterial infections
Rifampicin or phenytoin
Medicines that affect your immune system

Ask your HCP or pharmacist if you are not sure if you are taking any of these medicines.

What should I tell my HCP AFTER starting RINVOQ?
Tell your HCP right away if you:

Have any symptoms of an infection. RINVOQ can make you more likely to get infections or make any infections you have worse.
Have any signs or symptoms of blood clots during treatment with RINVOQ, including:

Swelling
Sudden unexplained chest pain
Pain or tenderness in the leg
Shortness of breath

Have a fever or stomach-area pain that does not go away, and a change in your bowel habits.

What are the common side effects of RINVOQ?
These include: upper respiratory tract infections (common cold, sinus infections), nausea, cough, and fever. These are not all the possible side effects of RINVOQ.

RINVOQ is taken once a day with or without food. Do not split, break, crush, or chew the tablet. Take RINVOQ exactly as your HCP tells you to use it.

This is the most important information to know about RINVOQ. For more information, talk to your HCP. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch or call 1-800-FDA-1088.

If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit AbbVie.com/myAbbVieAssist to learn more.

Please click here for the Full Prescribing Information and Medication Guide.

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Gastroenterology

With a robust clinical trial program, AbbVie is committed to cutting-edge research to drive exciting developments in inflammatory bowel diseases (IBD), like ulcerative colitis and Crohn's disease. By innovating, learning and adapting, AbbVie aspires to eliminate the burden of IBD and make a positive long-term impact on the lives of people with IBD. For more information on AbbVie in gastroenterology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.html.

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statements

Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2019 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

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