AbbVie Announces Upadacitinib (RINVOQ®) Met the Primary Endpoint in Phase 2 Clinical Trial of Vitiligo as Program Advances to Phase 3

• At week 24, upadacitinib met the primary endpoint of percent change from baseline in Facial Vitiligo Area Scoring Index (F-VASI) with 11 mg and 22 mg doses versus placebo in adults with non-segmental vitiligo (NSV)¹
• At week 52, the percent reduction from baseline in F-VASI was numerically greater than results at week 24 for all upadacitinib doses^1,2
• The safety profile was consistent with the known safety profile for upadacitinib^1,2

NORTH CHICAGO, Ill., Oct. 11, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that its Phase 2b study evaluating upadacitinib (RINVOQ^®) in adults with non-segmental vitiligo (NSV) met the primary endpoint of percent change from baseline in the Facial Vitiligo Area Scoring Index (F-VASI) at week 24 with the 11 mg and 22 mg doses versus placebo.¹ The percent reduction from baseline in F-VASI at week 52 was numerically greater than results at week 24 for all upadacitinib doses.² No new safety signals were identified beyond the known safety profile for upadacitinib. Based on these data, AbbVie is advancing its clinical program of upadacitinib in vitiligo to Phase 3.

"There is a high unmet need in vitiligo, with no systemic treatment options approved, leaving patients frustrated in seeking options for re-pigmentation of the skin," said Roopal Thakkar, M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie. "We will continue to apply our significant experience in advancing research and driving innovation in treatments for immune-mediated diseases, including underserved diseases with high burden on patients, such as vitiligo."

At week 24, upadacitinib achieved the primary endpoint of percent change from baseline (%CFB) in F-VASI with 11 mg and 22 mg doses versus placebo. F-VASI is a tool that measures re-pigmentation of the face and is used to assess the extent of re-pigmentation and treatment response in clinical trials.³ Higher response rates were also observed with upadacitinib versus placebo in secondary endpoints, including F-VASI 75 (≥75% reduction from baseline in F-VASI) at week 24 with the 11 mg and 22 mg doses and Total Vitiligo Area Scoring Index (T-VASI) 50 (≥50% reduction from baseline in T-VASI) at Week 24 with the 22 mg dose.

The mean percent reduction from baseline in F-VASI was numerically greater at week 52 than results at week 24 for all upadacitinib dose groups.² In addition, response rates observed for F-VASI 75 and T-VASI 50 at week 52 were numerically greater than those at week 24 for all upadacitinib dose groups.²

Among patients who continued upadacitinib treatment through week 52, %CFB in F-VASI and response rates for F-VASI 75 and T-VASI 50 were as follows:

"Vitiligo impacts millions of people globally, and there is no cure. The disease can have a great impact on patients' physical and mental health, as depigmentation of the skin can be severe," said Thierry Passeron, M.D., Ph.D., professor and chair, Department of Dermatology, Université Côte d'Azur. "In vitiligo, it can take time to see optimal skin re-pigmentation during treatment, which makes long-term studies critical to providing valuable insights on a treatment's meaningful impact for patients."

No new safety signals were observed beyond the known safety profile for upadacitinib.^1,2 Treatment-emergent adverse event (TEAE) rates were generally similar with upadacitinib and placebo in period 1 (most common TEAEs: COVID-19, acne, headache, and nasopharyngitis). Numerically higher rates of serious TEAEs and TEAEs leading to study drug discontinuation were observed in the upadacitinib 22 mg group versus the other groups. One death adjudicated as undetermined/unknown cause and deemed by the investigator to have no reasonable possibility of being related to study drug occurred in the upadacitinib 22 mg group (period 1). One adjudicated event of nonfatal ischemic stroke occurred with upadacitinib 11 mg (period 2) in a patient with known cardiovascular risk factors. One event of malignancy (breast cancer) occurred with upadacitinib 11 mg (period 2) in a patient with positive family history of breast cancer. Throughout the study, a single event of serious infection (COVID-19 pneumonia) was reported in the upadacitinib 22 mg group. There were no adjudicated events of venous thromboembolism, gastrointestinal perforation, or active tuberculosis.² The use of upadacitinib in vitiligo is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Vitiligo is a chronic, immune condition that affects up to 2% of the global population.⁴ The disease is unique to each patient, where white patches of depigmentation develop on the skin, most often around the mouth and eyes, fingers and wrists, armpits and groin.⁵ The most bothersome patches appear on the face, which makes F-VASI a key measure of clinical improvement in vitiligo for patients and dermatologists.³ NSV is the most common form of vitiligo – affecting approximately eight in 10 people with vitiligo⁶ – in which patches appear on both sides of the body symmetrically, and may spread over time.⁵ People with vitiligo can also experience an emotional and psychological burden that can impact their quality of life.⁴

The 24-week data in this release and partial 52-week data are being presented as an oral presentation during the European Academy of Dermatology and Venerology (EADV) Congress in Berlin, Germany, on October 12, 2023. The partial 52-week data is based on the data cutoff date of January 13, 2023. Approximately 58% of patients had an opportunity to reach 52-week at that time. The full 52-week data in this release will be presented at an upcoming medical meeting.

About the Phase 2 Study in Vitiligo^1,2
The 52-week, Phase 2b multicenter, randomized, double-blind, placebo-controlled study (NCT04927975) comprises two periods. Enrolled patients were aged 18–66 years with NSV, a Facial Vitiligo Area Scoring Index (F-VASI) of 1.1 and a Total Vitiligo Area Scoring Index (T-VASI) of 22, both mean scores at baseline. In period one, 185 patients (18 to 65 years old) were randomly assigned to once-daily upadacitinib 22 mg (N=43), upadacitinib 11 mg (N=47), upadacitinib 6 mg (N=49), or placebo (N=46) for 24 weeks of treatment. 166 patients (89.7%) continued to a 28-week blinded extension (period two). In period two, patients receiving upadacitinib during period one continued their respective regimens (upadacitinib 22 mg, N=33; upadacitinib 11 mg, N=45; upadacitinib 6 mg, N=45); patients who received placebo in period one were pre-assigned to receive either upadacitinib 11 mg (N=21) or upadacitinib 22 mg (N=22) in period 2.

About RINVOQ^® (upadacitinib)⁸ 
Discovered and developed by AbbVie scientists, RINVOQ is a JAK inhibitor with seven approved indications and is currently being studied in several immune-mediated diseases.^7,8 In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.⁸ The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.

Use of upadacitinib in vitiligo is not approved and its safety and efficacy have not been evaluated by regulatory authorities.  

EU Indications and Important Safety Information about RINVOQ^® (upadacitinib)⁸

Indications

Rheumatoid arthritis
RINVOQ is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate.

Psoriatic arthritis
RINVOQ is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs. RINVOQ may be used as monotherapy or in combination with methotrexate.

Axial spondyloarthritis

Non-radiographic axial spondyloarthritis (nr-axSpA)

RINVOQ is indicated for the treatment of active non-radiographic axial spondyloarthritis in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have responded inadequately to nonsteroidal anti- inflammatory drugs (NSAIDs).

Ankylosing spondylitis (AS, radiographic axial spondyloarthritis)

RINVOQ is indicated for the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy.

Atopic dermatitis
RINVOQ is indicated for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy.

Ulcerative colitis
RINVOQ is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.

Crohn's disease
RINVOQ is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.

Important Safety Information

Contraindications
RINVOQ is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy.

Special warnings and precautions for use
RINVOQ should only be used if no suitable treatment alternatives are available in patients:

-  65 years of age and older;
-  patients with history of atherosclerotic cardiovascular (CV) disease or other CV risk factors (such as current or past long-time smokers);
-  patients with malignancy risk factors (e.g. current malignancy or history of malignancy)

Use in patients 65 years of age and older
Considering the increased risk of MACE, malignancies, serious infections, and all-cause mortality in patients ≥65 years of age, as observed in a large randomised study of tofacitinib (another JAK inhibitor), RINVOQ should only be used in these patients if no suitable treatment alternatives are available. In patients ≥65 years of age, there is an increased risk of adverse reactions with RINVOQ 30 mg once daily. Consequently, the recommended dose for long-term use in this patient population is 15 mg once daily.

Immunosuppressive medicinal products
Use in combination with other potent immunosuppressants is not recommended.

Serious infections
Serious and sometimes fatal infections have been reported in patients receiving RINVOQ. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis and sepsis have been reported with RINVOQ. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis have been reported. RINVOQ should not be initiated in patients with an active, serious infection, including localized infections. RINVOQ should be interrupted if a patient develops a serious or opportunistic infection until the infection is controlled. A higher rate of serious infections was observed with RINVOQ 30 mg compared to 15 mg. As there is a higher incidence of infections in the elderly and patients with diabetes in general, caution should be used when treating these populations. In patients ≥65 years of age, RINVOQ should only be used if no suitable treatment alternatives are available.

Tuberculosis
Patients should be screened for TB before starting RINVOQ. RINVOQ should not be given to patients with active TB. Anti-TB therapy may be appropriate for select patients in consultation with a physician with expertise in the treatment of TB. Patients should be monitored for the development of signs and symptoms of TB.

Viral reactivation
Viral reactivation, including cases of herpes zoster, was reported in clinical studies. The risk of herpes zoster appears to be higher in Japanese patients treated with RINVOQ. Consider interruption of RINVOQ if the patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should occur before and during therapy. If hepatitis B virus DNA is detected, a liver specialist should be consulted.

Vaccination
The use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunizations, including prophylactic zoster vaccinations, prior to initiating RINVOQ, in agreement with current immunization guidelines.

Malignancy
Lymphoma and other malignancies have been reported in patients receiving JAK inhibitors, including RINVOQ. In a large randomised active–controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a higher rate of malignancies, particularly lung cancer, lymphoma, and non-melanoma skin cancer (NMSC), was observed with tofacitinib compared to tumour necrosis factor (TNF) inhibitors. A higher rate of malignancies, including NMSC, was observed with RINVOQ 30 mg compared to 15 mg. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. In patients ≥65 years of age, patients who are current or past long-time smokers, or patients with other malignancy risk factors (e.g., current malignancy or history of malignancy), RINVOQ should only be used if no suitable treatment alternatives are available.

Hematological abnormalities
Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management.

Gastrointestinal Perforations
Events of diverticulitis and gastrointestinal perforations have been reported in clinical trials and from post–marketing sources. RINVOQ should be used with caution in patients who may be at risk for gastrointestinal perforation (e.g., patients with diverticular disease, a history of diverticulitis, or who are taking nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, or opioids. Patients with active Crohn's disease are at increased risk for developing intestinal perforation. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation.

Major adverse cardiovascular events
MACE were observed in clinical studies of RINVOQ. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a higher rate of MACE, defined as CV death, non-fatal myocardial infarction and non-fatal stroke, was observed with tofacitinib compared to TNF inhibitors. Therefore, in patients ≥65 years of age, patients who are current or past long-time smokers, and patients with history of atherosclerotic CV disease or other CV risk factors, RINVOQ should only be used if no suitable treatment alternatives are available.

Lipids
RINVOQ treatment was associated with dose-dependent increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol.

Hepatic transaminase elevations
Treatment with RINVOQ was associated with an increased incidence of liver enzyme elevation. If alanine transaminase (ALT) or aspartate transaminase (AST) increases are observed and drug-induced liver injury is suspected, RINVOQ should be interrupted until this diagnosis is excluded.

Venous thromboembolism
Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) were observed in clinical trials for RINVOQ. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a dose–dependent higher rate of VTE including DVT and PE was observed with tofacitinib compared to TNF inhibitors. In patients with CV or malignancy risk factors, RINVOQ should only be used if no suitable treatment alternatives are available. In patients with known VTE risk factors other than CV or malignancy risk factors (e.g. previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, and inherited coagulation disorder), RINVOQ should be used with caution. Patients should be re-evaluated periodically to assess for changes in VTE risk. Promptly evaluate patients with signs and symptoms of VTE and discontinue RINVOQ in patients with suspected VTE.

Hypersensitivity reactions
Serious hypersensitivity reactions such as anaphylaxis and angioedema have been reported in patients receiving RINVOQ. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy.

Adverse reactions
The most commonly reported adverse reactions in RA, PsA, and axSpA clinical trials (≥2% of patients in at least one of the indications) with RINVOQ 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, ALT increased, bronchitis, nausea, neutropenia, cough, AST increased, and hypercholesterolemia. Overall, the safety profile observed in patients with psoriatic arthritis or active axial spondyloarthritis treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with RA.

The most commonly reported adverse reactions in AD trials (≥2% of patients) with RINVOQ 15 mg or 30 mg were upper respiratory tract infection, acne, herpes simplex, headache, blood CPK increased, cough, folliculitis, abdominal pain, nausea, neutropenia, pyrexia, and influenza. Dose dependent increased risks of infection and herpes zoster were observed with RINVOQ. The safety profile for RINVOQ 15 mg in adolescents was similar to that in adults. The safety and efficacy of the 30 mg dose in adolescents are still being investigated.

The most commonly reported adverse reactions in the UC and CD trials (≥3% of patients) with RINVOQ 45 mg, 30 mg or 15 mg were upper respiratory tract infection, pyrexia, blood CPK increased, anemia, headache, acne, herpes zoster, neutropaenia, rash, pneumonia, hypercholesterolemia, bronchitis, aspartate transaminase increased, fatigue, folliculitis, alanine transaminase increased, herpes simplex, and influenza.

The overall safety profile observed in patients with UC was generally consistent with that observed in patients with RA.

Overall, the safety profile observed in patients with CD treated with RINVOQ was consistent with the known safety profile for RINVOQ.

The most common serious adverse reactions were serious infections.

The safety profile of upadacitinib with long–term treatment was generally similar to the safety profile during the placebo–controlled period across indications.

This is not a complete summary of all safety information.

See RINVOQ full Summary of Product Characteristics (SmPC) at www.ema.europa.eu

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

About AbbVie in Dermatology
For more than a decade, AbbVie has worked to uncover new solutions and improve care for people with serious skin diseases, including psoriasis, psoriatic arthritis, hidradenitis suppurativa and atopic dermatitis. With a broad clinical trial program, we continue to actively research and adapt to the evolving needs of the dermatology community and advance our pipeline to help people achieve their treatment goals and live beyond their skin disease. For more information, visit AbbVie in dermatology.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions 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, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn,Facebook, Instagram, X (formerly Twitter), and YouTube.

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 and uses of future or conditional verbs, 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 expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 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 2022 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, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References

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