For 20 years, AbbVie’s adalimumab (Humira®) has been one of the world’s top-selling products. However, the US drug expiry in January 2023 resulted in a 32% decline in sales of adalimumab, accompanied by a 7% drop in the company’s total revenue for that year. As further sharp declines are expected for adalimumab , AbbVie has strategically pivoted to alternative immunology products to bolster its revenue streams.*

As such, two drugs, risankizumab (Skyrizi®) and upadacitinib (Rinvoq®), are emerging as key replacements. According to GlobalDate, a leading data and analytics company, these products are forecast to collectively generate over 2US $ 32 billion by 2030, enabling AbbVie to financially rebound and continue its position as a leading immunology player.

From its initial Food and Drug Administration (FDA) approval in 2002 to 2023, adalimumab generated US $ 187 billion for AbbVie. This antibody has been the global market leader in immunology, with key indications including plaque psoriasis, as well as psoriatic and rheumatoid arthritis. A sales peak of US $ 21.2 billion in 2022 accounted for 37% of AbbVie’s total revenue. However, a loss of US market exclusivity in January 2023 saw drug sales plummet to $14.4 billion. This reduction in sales was, in part, due to the influx of biosimilars. In 2023, AbbVie’s total sales also dropped by 7%, highlighting adalimumab’s pivotal role within the company.

Investing in alternatives
“Anticipating this eventuality, AbbVie invested into alternative products within its immunology portfolio, risankizumab and upadacitinib.

Risankizumab is an interleukin (IL)-23 inhibitor that selectively blocks IL-23 by binding to its p19 subunit.  IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases. [1][2] The drug was first approved in Japan in March 2019, but has now also been approved by the U.S. Food and Drug Administration for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn’s disease.

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On May 31, 2024 European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of risankizumab for the treatment of adults with moderately to severely active UC who have had an inadequate response, lost response, or were intolerant to either conventional or biologic therapy. The recommended induction dose is 1200 mg intravenous (IV), followed by a maintenance dose of 180 mg or 360 mg subcutaneous (SC), based on individual patient presentation. The final European Commission decision is expected in the third quarter of 2024.

“Results from the INSPIRE and COMMAND Phase 3 trials show that patients with moderately to severely active UC can strive for long-term management goals that go beyond symptom control, including histologic-endoscopic mucosal healing,” explained Edouard Louis, M.D., Ph.D., professor and head of gastroenterology, Liège University Hospital; dean of faculty, Liège University; and INSPIRE trial investigator.

“This finding is significant since treatment goals for patients are evolving beyond symptom management to include endoscopic remission. [3][4][5] Studies have shown that endoscopic improvement may be associated with favorable longer-term outcomes, including lower risk of hospitalizations and improved quality of life.”[6][7][8]

The CHMP positive opinion is supported by data from two Phase 3 clinical trials: the INSPIRE induction trial and the COMMAND maintenance trial. The INSPIRE trial evaluated 1200 mg of IV risankizumab administered as an induction dose at 0, 4 and 8 weeks in patients with moderately to severely active UC. In the COMMAND trial, patients who responded to induction treatment in INSPIRE were rerandomized to receive 180 mg or 360 mg of SC risankizumab as maintenance doses for an additional 52 weeks. The safety profile of risankizumab in both trials was consistent with the safety profile observed in previous trials across other indications, with no new safety risks observed.

“At AbbVie, patients are at the heart of everything we do,” said Kori Wallace, M.D., Ph.D., vice president, immunology clinical development, AbbVie. “We are motivated to bring new treatment options to patients in need through our commitment to ongoing research and development in gastroenterology. We eagerly await the EMA’s final decision for risankizumab on its use in UC which has the potential to help patients meet their long-term treatment goals.”

Upadacitinib
In August 2019 of the same year, upadacitinib, a small molecule Janus kinase (JAK) inhibitor, was first approved for the United States. These drugs are forecast to offset and combat the losses in revenue experienced by AbbVie,” said Jasper Morley, Pharma Analyst at GlobalData.

Risankizumab generated US $ 7.7 billion in 2023 for indications like plaque psoriasis, Crohn’s disease, and psoriatic arthritis. With expected regulatory approvals for ulcerative colitis later this year, risankizumab sales are forecast to peak in 2030, reaching US $ 19.7 billion.

Upadacitinib, which is approved for indications like rheumatoid arthritis, spondyloarthritis, and atopic dermatitis, achieved US $ 4 billion in sales in 2023, with a forecast to increase and peak at US $ 12.3 billion by 2030.

“Like adalimumab, risankizumab and upadacitinib are within AbbVie’s immunology portfolio and cover adalimumab’s major indications, such as psoriasis and arthritis. Given their 2030 drug expiries, these drugs are estimated to not only bolster sales for an extended period of time, but also maintain and increase AbbVie’s market shares in the immunological areas adalimumab once dominated,” Morley noted.

With the forecast success of both risankizumab and upadacitinib, AbbVie is predicted to recover from the 2023 drop in sales. By 2030, the company is forecast to generate total revenue of US $ 75.4 billion, a 39% increase from 2023. In 2030, risankizumab and upadacitinib are forecast to collectively generate over US $ 32 billion, accounting for 42% of AbbVie’s total revenue.

Oncology
In addition risankizumab and upadacitinib AbbVie is also creating a strong pipeline with the company’s innovative antibody-drug conjugate (ADC) platform which will be showcased across three oral presentations at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting (May 31 – June 4, 2024).

AbbVie’s ADCs are designed to target unique protein biomarkers such as c-Met (MET protein) and SEZ6 (seizure-related homolog 6 protein), which are over-expressed across various tumor types. By utilizing these biomarkers as targets, ADCs are designed to deliver potent cancer cell death-inducing agents called ‘payloads’ to the tumor.

“In anticipation of adalimumab’s drug expiry, AbbVie has strategically redirected its focus towards alternative immunology products like risankizumab and upadacitinib and novel oncology-focused (investigational) agents. These drugs are poised for long-term sales growth, enabling the company to not only financially recover from adalimumab’s expiry, but to also continue its position as a formidable player within the immunology therapy area,” Morley concluded.

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Note: * AbbVie is a specialty biopharmaceutical company, which discovers, develops, manufactures, and commercializes drugs for the treatment of chronic and complex diseases. Its drugs are indicated for the treatment of metabolic and rheumatological diseases, neurological disorders, skin diseases, rheumatoid arthritis, pain related to endometriosis, pediatric Crohn’s disease, cancer, and other serious health conditions. AbbVie is also advancing its pipeline programs for the treatment of Crohn’s disease, Parkinson’s disease, neurological disorders, aesthetics, and other autoimmune diseases. The company markets its products directly to wholesalers, distributors, healthcare facilities, government agencies, specialty pharmacies, and independent retailers. The company has operations in the Americas, Asia-Pacific, Europe, the Middle East and Africa. AbbVie is headquartered in North Chicago, Illinois, the US.

Clinical trials
A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study to Evaluate the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Ulcerative Colitis – ClinicalTrials.gov ID NCT03398148
A Study to Assess the Efficacy and Safety of Risankizumab in Participants With Ulcerative Colitis ClinicalTrials.gov ID NCT03398135

Highlights of prescribing information
Adalimumab (Humira®; AbbVie) [Prescribing Information]
Risankizumab (Skyrizi®; AbbVie) [Prescribing Information]
Upadacitinib (Rinvoq®; AbbVie) [Prescribing Information]

Reference
[1] Duvallet, E. et al. (2011) “Interleukin-23: A Key Cytokine in Inflammatory Diseases.” Ann Med. 43(7):503-511. doi:10.3109/07853890.2011.577093.
[2] Moschen, A.R. et al. (2019) “IL-12, IL-23 and IL-17 in IBD: Immunobiology and Therapeutic Targeting.” Nat Rev Gastroenterol Hepatol.16(3):185-196. doi:10.1038/s41575-018-0084-8.
[3] Van Assche, G. et al. (2016) “Burden of Disease and Patient-Reported Outcomes in Patients With Moderate to Severe Ulcerative Colitis in the Last 12 Months – Multicenter European Cohort Study.” Dig Liver Dis. 48(6):592-600. doi:10.1016/j.dld.2016.01.011.
[4] Dave, M. Loftus, EV Jr. (2012) “Mucosal Healing in Inflammatory Bowel Disease-A True Paradigm of Success?” Gastroenterol Hepatol (N Y). 8(1):29-38.
[5] Turner, D. et al. (2021) “STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target Strategies in IBD.” Gastroenterology. 160(5):1570-1583. doi:10.1053/j.gastro.2020.12.031.
[6] Colombel, J.F. et al. (2020) “Outcomes and Strategies to Support a Treat-to-Target Approach in Inflammatory Bowel Disease: A Systematic Review.” J Crohns Colitis. 14(2):254-266. doi:10.1093/ecco-jcc/jjz131.
[7] Picco ,M.F., Farraye, F.A. (2019) “Targeting Mucosal Healing in Crohn’s Disease.” Gastroenterol Hepatol (N Y). 15(10):529-538.
[8] Armuzzi, A. et al. (2020) “The Association Between Disease Activity and Patient-Reported Outcomes in Patients With Moderate-to-Severe Ulcerative Colitis in the United States and Europe.” BMC Gastroenterol. 20(1):18. doi:10.1186/s12876-020-1164-0.

Featured image: © 2024 PhRMA/Native Content project at Abbott Labs in Chicago, IL. Still photo by Kevin J. Miyazaki/Redux. Used with permission.

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