AbbVie’s Humira® (Adalimumab) Approved in China for Moderate to Severe Active Crohn’s Disease in Adults

− Humira^®(Adalimumab Injection) has been approved by the National Medical Products Administration (NMPA) of China for the treatment of moderate to severe active Crohn's disease in adults.

− Crohn’s disease is a severe, chronic inflammatory disorder of the gastrointestinal tract. Currently, there is no cure for Crohn’s disease in clinical practice; innovative therapeutic approaches and medications are needed to control disease progression, reduce complications, and improve patients’ quality of life.^{[1], [2]}。

− Phase 3 clinical study results of Humira in China showed that Humira^®(Adalimumab Injection) can induce and maintain clinical remission in Chinese patients with moderately to severely active Crohn's disease; these results are consistent with those from global clinical studies. The overall safety profile of HUMIRA® (Adalimumab Injection) is comparable to that of placebo, and no unexpected safety signals were observed in the Chinese population.^[3]. Multiple real-world studies have shown^[4], Humira^®(Adalimumab Injection) is considered the preferred first-line biologic agent for the treatment of Crohn's disease in its approved countries.^{[5], [6]}。

− Humira^®(Adalimumab Injection) is a fully human monoclonal antibody against tumor necrosis factor. It has more than 15 approved indications for immune-mediated diseases worldwide. Crohn's disease is one of the indications for Humira.^®(Adalimumab Injection) The fifth indication approved in China, also marking Humira^®(Adalimumab Injection) has entered a brand-new therapeutic area in China—gastroenterology—following its previous expansions into rheumatology and immunology, dermatology, and pediatrics.

SHANGHAI, Jan. 14, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global leading biopharmaceutical company, announced that the China National Medical Products Administration (NMPA) had approved Humira on January 8, 2020^®(Adalimumab Injection) is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response, intolerance, or contraindication to adequate corticosteroid and/or immunosuppressive therapy. This is Humira.^®(Adalimumab Injection) the fifth indication approved in China, also marking Humira^®(Humira Injection) has entered a brand-new therapeutic area in China—gastroenterology—following its previous expansions into rheumatology and immunology, dermatology, and pediatrics.^®(Adalimumab Injection) is currently the first fully human anti-tumor necrosis factor (TNFi) monoclonal antibody approved in China for the treatment of Crohn's disease.

This approval is based on the results of two pivotal clinical studies, including one evaluating adalimumab (Humira) in patients with moderately to severely active Crohn’s disease in China^®) Phase 3 study on the efficacy and safety of inducing and maintaining clinical remission. The study showed: adalimumab (Humira^®) for the treatment of patients who have failed prior corticosteroid and/or immunosuppressive therapy and have elevated high-sensitivity C-reactive protein (>=3 mg/L) moderate-to-severe active Crohn's disease (CDAI>= 220 to <=450) In Chinese adult patients, it was able to induce and maintain clinical remission in Chinese patients with moderately to severely active Crohn’s disease compared with the placebo group; these results are consistent with those from global clinical studies. The overall safety profile of HUMIRA® (adalimumab injection) was comparable to that of placebo, and no unexpected safety signals were observed in the Chinese population.^[3]。

“Crohn’s disease is a chronic, progressive, inflammatory gastrointestinal disorder characterized by a prolonged course and a tendency to relapse. Currently, there is no cure, posing significant challenges to patients’ daily lives,” stated Professor Chen Minhu, Chairman of the Chinese Society of Gastroenterology under the Chinese Medical Association, Vice President of the First Affiliated Hospital of Sun Yat-sen University, Academic Leader of Gastroenterology, and Lead Investigator of the Phase 3 Clinical Study of Adalimumab for Crohn’s Disease in China. “Multiple clinical studies^[7]and real-world study data show^[8], Fully Human Anti-TNF Monoclonal Antibody -- Humira^®(Adalimumab Injection) can effectively improve the symptoms of Crohn's disease, promote mucosal healing and fistula closure, with good safety, low incidence of adverse reactions, and good patient tolerance. In addition, Humira^®(Adalimumab Injection) is administered via subcutaneous injection using a pre-filled syringe device, offering convenience and time savings. Humira^®(Adalimumab Injection) provides patients with an excellent treatment option, expected to help control disease progression, improve quality of life, and enable a return to normal daily living.”

Symptoms of Crohn's disease include chronic diarrhea, abdominal pain, weight loss, loss of appetite, fever, and rectal bleeding, which severely impact patients' quality of life.^{[1], [2]}。According to meta-analysis estimates, the prevalence of Crohn's disease in China is 2.29 per 100,000 population, and the incidence is 0.848 per 100,000 population, showing a rapid upward trend in recent years.^{[9], [10]}。Currently, Crohn's disease is incurable in clinical practice, necessitating innovative therapeutic approaches and medications to control disease progression, reduce complications, and improve patients' quality of life.^{[1], [2]}。

Ossian, General Manager of AbbVie China, stated: “We are delighted that Humira^®Provides a novel and effective treatment option for patients in China with moderate-to-severe active Crohn’s disease. This approval once again underscores AbbVie’s commitment to continuously improving treatments for patients with immune-mediated diseases worldwide. Humira^®More than 15 immune-mediated disease-related indications have been approved worldwide. We will continue our efforts to bring Humira^®“More indications and other innovative products will be introduced to China at a faster pace to meet the unmet needs of Chinese patients. Meanwhile, we will spare no effort to actively collaborate with all sectors of society, ensuring that these innovative therapies truly benefit a wide range of patients in China.”

Humira^®(Adalimumab Injection) The indication for Crohn's disease was approved in the United States and the European Union in 2007. In the United States, Humira^®(Adalimumab Injection) The indication for Crohn's disease was granted "Fast Track Designation" by the U.S. Food and Drug Administration (FDA).”under the circumstances.

RepairMeile^®Key Clinical Study Data for the Treatment of Moderate to Severe Crohn's Disease in Adults^[3]

APhase 3, A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Adalimumab in Inducing and Maintaining Clinical Remission in Chinese Subjects with Moderately to Severely Active Crohn’s Disease and Elevated High-Sensitivity C-Reactive Protein

Study results demonstrated that the adalimumab group achieved the primary efficacy endpoint of clinical remission (CDAI <150) at Week 4 compared with the placebo group; the key secondary endpoint, defined as clinical remission (CDAI <150) at Week 26 among subjects who exhibited a clinical response at Week 8, exceeded the prespecified threshold of a 30% clinically meaningful response rate. Compared with placebo, adalimumab induced and maintained clinical remission in Chinese patients with moderately to severely active Crohn’s disease; these findings are consistent with those from global clinical studies. The overall safety profile of HUMIRA® (adalimumab injection) was comparable to that of placebo, and no unexpected safety signals were observed in the Chinese population.^[3]

AA Phase 2, Randomized, Double-Blind, Multicenter Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Two Adalimumab Dosing Regimens in Chinese Subjects with Moderately to Severely Active Crohn’s Disease and Elevated High-Sensitivity C-Reactive Protein^[11]

Efficacy results confirmed that, compared with the adalimumab 80/40 mg regimen, Chinese subjects with moderately to severely active Crohn’s disease and elevated hs-CRP levels achieved clinical remission and clinical response more rapidly with the adalimumab 160/80 mg regimen, along with faster improvements in objective disease markers (hs-CRP and fecal calprotectin). Clinical response was achieved by Week 2 with the adalimumab 160/80 mg regimen and sustained through Week 8 (end of the double-blind treatment period). Efficacy results from the open-label extension phase (Weeks 8 to 26) confirmed that the majority of subjects in both treatment groups maintained sustained clinical response and clinical remission while continuing open-label adalimumab 40 mg every other week (eow).

Based on the adverse events, laboratory results, and vital signs assessments through Week 26, it was confirmed that adalimumab administered at doses of 80/40 mg or 160/80 mg at Weeks 0/2, followed by 40 mg every two weeks thereafter, generally demonstrated a favorable safety and tolerability profile.

About Crohn's Disease

Crohn's disease is an inflammatory bowel disease that encompasses a spectrum of clinical and pathological processes, characterized by focal, asymmetric, transmural inflammation that can affect any part of the gastrointestinal tract, sometimes accompanied by granuloma formation; the disease primarily affects the ileum and colon. Clinical features of moderate-to-severe disease include strictures that can obstruct the bowel, abscesses, and fistulas.^{[1], [2]}。

Typical symptoms of Crohn's disease include chronic diarrhea, abdominal pain, weight loss, decreased appetite, fever, and rectal bleeding, all of which impact patients' quality of life.^[12]。

Crohn's disease can affect individuals of any age, but it is most common in people aged 20–30 years.^[1]。In Western countries, the prevalence is slightly higher in women than in men, with certain ethnic groups having a higher risk of disease.^{[7], [13]}。In China, there are slightly more male patients than female patients.^[14]。

The incidence of Crohn's disease in Asia is lower than that in the West, ranging from 0.14 to 1.22 cases per 100,000 population.^{[6],[15],[16]}。Meta-analysis estimates that the prevalence of Crohn's disease in China is 2.29 per 100,000 population, with an incidence rate of 0.848 per 100,000 population. In mainland China, the trends in both prevalence and incidence of Crohn's disease have risen rapidly over time, and it is no longer considered a rare disease.^{[6], [7]}。

Currently, Crohn's disease is incurable in clinical practice, necessitating innovative therapeutic approaches and medications to control disease progression, reduce complications, and improve patients' quality of life.^{[1], [2]。}

About Humira^®(Adalimumab Injection)

Humira^®(Adalimumab Injection) is the world's first fully human monoclonal antibody against tumor necrosis factor approved for marketing. Excessive inflammation in various immune-mediated diseases in humans is associated with tumor necrosis factor-alpha (TNF-α), Humira^®(Adalimumab Injection) can selectively bind to TNF-α molecules, preventing their attachment to healthy cells, thereby reducing damage caused by excessive TNF-α. Based on this principle, Humira^®(Adalimumab Injection) can be used to treat various immune-mediated diseases.

Humira, since its market launch in 2003^®(Adalimumab Injection) has helped numerous patients with immune diseases worldwide. Currently, Humira^®(Adalimumab Injection) has received approval for 17 indications worldwide. At least one indication has been approved in more than 100 countries and regions globally. Currently, over 1 million patients worldwide are using Humira.^®(Adalimumab Injection) treatment. Globally, Humira^®(Adalimumab Injection) has over 20 years of research data, more than 100 clinical studies, and covers over 33,000 patients.

Humira^®(Adalimumab Injection) is administered via two methods: pre-filled syringes and pre-filled injection pens (“Humira Pen”). The pre-filled injection pen offers convenient use, allowing patients to self-administer the injection under the guidance of qualified healthcare professionals.

In China, Humira^®(Adalimumab Injection) was launched in 2010 and has currently been approved for five indications: rheumatoid arthritis (approved in 2010), ankylosing spondylitis (approved in 2013), moderate-to-severe plaque psoriasis (approved in 2017), polyarticular juvenile idiopathic arthritis (approved in 2019), and moderately to severely active Crohn's disease in adults (approved in 2020). In 2018, the National Medical Products Administration (NMPA) of China approved Humira.^®(Adalimumab Injection) The indicated population for adult psoriasis has been changed to “adult patients with moderate-to-severe chronic plaque psoriasis who require systemic therapy,” shifting its status from a second-line systemic therapy to a first-line systemic therapy in clinical practice. Meanwhile, the NMPA also approved Humira^®(Adalimumab Injection) Add the results of clinical trials on psoriatic nails to the package insert in China.

Currently, Humira^®(Adalimumab Injection) has been included in the "National Reimbursement Drug List for Basic Medical Insurance, Work-Related Injury Insurance, and Maternity Insurance," with covered indications including rheumatoid arthritis, ankylosing spondylitis, and moderate-to-severe plaque psoriasis. In the future, Humira^®(Humira [adalimumab injection]) is expected to continue expanding into new indications and dosage forms.^®(Adalimumab Injection) Indications for the Treatment of Non-infectious Intermediate Uveitis, Posterior Uveitis, and Panuveitis^[17]It has been included in China's second batch of the List of Overseas New Drugs Urgently Needed for Clinical Use.

About AbbVie

AbbVie is a research-driven global biopharmaceutical company dedicated to developing and promoting industry-leading innovative therapies to address some of the world’s most complex and challenging health issues. Leveraging specialized expertise, dedicated employees, and a unique approach to innovation, AbbVie focuses on advancing treatments in four core therapeutic areas: immunology, oncology, virology, and neuroscience. With employees in more than 75 countries worldwide, AbbVie is working together to make a significant impact on people’s lives and improve global health.

AbbVie China is headquartered in Shanghai, focusing on four major therapeutic areas: immunology, virology, nephrology, and anesthesiology, with plans to expand into oncology in the future. Please scan the QR code below to follow AbbVie China’s official WeChat account for more information.

Forward-Looking Statements

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For additional information on economic, competitive, governmental, technological, and other factors that may affect AbbVie, please refer to Item 1A “Risk Factors” in AbbVie’s Annual Report on Form 10-K for the year 2013 and Part II, Item 1A “Risk Factors” in AbbVie’s Quarterly Report on Form 10-Q for the second quarter of 2014, both of which have been filed with the U.S. Securities and Exchange Commission. Except as required by law, AbbVie undertakes no obligation to publicly update any forward-looking statements as a result of subsequent events or developments.

[1] World Gastroenterology Organisation Global Guidelines: IBD Diagnosis and Management. 2010;16(1):112-24.

[2] "Crohn's Disease: Treatment Options and a Review of Current Research" 2013;286(1-2):45-52.

[3] B Chen, et al.  Efficacy and Safety of Adalimumab in Chinese Patients With Moderately to Severely Active Crohn’s Disease. AOCC 2018. Poster PO 021

[4] Real-world evidence derived from non-controlled clinical trials has inherent limitations

[5] Anisdahl K et al. Crohn's colitis. 2019; 13(Suppl 1): S475-6.

[6] Brady JE et al. Clinical Therapeutics. 2018; 40(9): 1509-21.

[7] Key clinical study data of Humira® for the treatment of moderate to severe Crohn’s disease in adults;

[8] Real-world evidence derived from non-controlled clinical trials has inherent limitations.

[9] “Prevalence and Incidence of Crohn’s Disease in Mainland China: A Meta-analysis of 55 Years of Research” 2010;11(3):161-6.

[10] International Journal of Colorectal Disease - Epidemiology of inflammatory bowel disease in different ethnic and religious groups: limitations of clues to etiology. 1996;11(1):25-8

[11] Kai-Chun Wu, et al. Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn’s disease. Intest Res 2016;14(2):152-163

[12] Gastroenterology-Clinical Epidemiology of Inflammatory Bowel Disease: Incidence, Prevalence, and Environmental Influences. 2004;126(6):1504-17.

[13] "Gastroenterology - Incidence and Phenotype of Inflammatory Bowel Disease Based on Results from the Asia-Pacific Crohn's Disease and Colitis Epidemiology Study" 2013;145(1):158-65.

[14] IBD Group, Chinese Society of Gastroenterology, Chinese Medical Association. Chin J Dig. 2018;38(5):292-311

[15] “Inflammatory Bowel Disease in Mainland China: The First Population-Based Prospective Study on the Incidence of Inflammatory Bowel Disease—The Emergence of a ‘Western’ Disease.” 2013;19(9):1839-45.

[16] “A Prospective Population-Based Study: Incidence and Clinical Characteristics of Inflammatory Bowel Disease in Developed Areas of Guangdong Province, China” 2013;28(7):1148‑53.

[17] This indication is currently under registration with the National Medical Products Administration (NMPA) of China, but has not yet received marketing authorization.