AbbVie 2023: Passing the torch

With Humira finally losing exclusivity and market share, a new generation of autoimmune drugs is entering the spotlight at AbbVie.

By Joshua Slatko • [email protected]

 

AbbVie

1 North Waukegan Road

North Chicago, IL 60064-6400

847-932-7900 • abbvie.com

 

Financial Performance
	2022	2021	1H 2023	1H 2022
Revenue	$58,054	$56,197	$26,090	$28,121
Net income	$11,845	$11,549	$2,268	$5,421
Diluted EPS	$6.63	$6.45	$1.26	$3.03
R&D Expense	$6,510	$6,922	$4,025	$3,106
All figures are in millions of dollars, except EPS.

Best-selling products

All sales are in millions of dollars.

2022 sales

• Humira $21,237 
• Skyrizi $5,165 
• Imbruvica $4,568 
• Botox Therapeutic $2,719 
• Botox Cosmetic $2,615 
• Rinvoq $2,522 
• Vraylar $2,038 
• Venclexta $2,009 
• Mavyret $1,541 
• Juvederm Collection $1,428 
• Creon $1,278
• Linzess $1,035 
• Ubrelvy $680
• Restasis $666 
• Lumigan $514

1H 2023 sales

• Humira $7,553 
• Skyrizi $3,243 
• Imbruvica $1,785 
• Rinvoq $1,604 
• Botox Therapeutic $1,467 
• Botox Cosmetic $1,344 
• Vraylar $1,219 
• Venclexta $1,109 
• Mavyret $751 
• Juvederm Collection $723 
• Creon $587 
• Linzess $537 
• Ubrelvy $348

Outcomes Creativity Index Score: 13

• Manny Awards — 6
• Cannes Lions — N/A
• Clio Health — N/A
• Creative Floor Awards — 4
• LIA: Pharma/Health & Wellness – 3
• MM+M Awards — N/A
• One Show — N/A

 

2022 was likely Humira’s swan song as one of the world’s leading prescription medicines by sales. The iconic brand generated more than $20 billion in revenue for AbbVie yet again, but its loss of exclusivity in the United States at the end of January 2023 means that the best-selling drug of the past decade is finally on a downswing. That said, company leaders are confident that they are prepared for what’s next, and with the fast-growing autoimmune products Skyrizi and Rinvoq both topping 50 percent in growth in 2022, they might be right.

“2022 was another highly productive year capping a decade of outstanding performance,” said AbbVie CEO Richard Gonzalez in the company’s annual financial results announcement. “Since our inception, we have built a diverse portfolio of growth products with significant leadership positions, developed a robust pipeline of innovative assets, and created a culture of strong execution. Looking forward, we have a solid foundation which will allow us to absorb the U.S. Humira loss of exclusivity, return to strong top-line growth in 2025, and drive top-tier financial performance over the long term.”

AbbVie’s top-line sales were $58.05 billion in 2022, an improvement of 3.3 percent over the previous year. Net income rose 2.6 percent to $11.85 billion, and earnings per share were up 18 cents to $6.63. In the first half of 2023 the top line declined by 7.2 percent to $26.09 billion, dragged down largely by Humira’s loss of exclusivity in January and subsequent revenue decline. Net income fell from $5.42 billion to $2.27 billion with EPS declining accordingly from $3.03 to $1.26. This, however, was impacted by a large charge for changes in fair value of contingent consideration liabilities of $3.22 billion reflecting higher estimated Skyrizi sales driven by stronger market share uptake, compared with a $757 million charge in the first half of 2022. Company leaders are projecting an adjusted diluted EPS in the $10.90 – $11.10 range for full-year 2023.

Acquisitions & collaborations

In January, AbbVie and Anima Biotech announced a collaboration to discover and develop mRNA biology modulators for three targets across oncology and immunology. Anima will use its mRNA Lightning platform to discover novel mRNA biology modulators against the collaboration targets providing AbbVie exclusive rights to license and further develop and commercialize the programs.

Under the terms of the agreement, Anima received an upfront payment of $42 million and may be eligible to receive up to $540 million in option fees and research and development milestones in the aggregate across the three targets, with potential for further commercial milestones as well as tiered royalties on net sales. AbbVie has an option to expand the collaboration with up to three additional targets under the same terms as the initial collaboration, which may increase the potential value of the collaboration.

That same month, AbbVie and Immunome Inc., a clinical-stage biopharmaceutical company that utilizes its human memory B cell platform to discover and develop first-in-class antibody therapeutics, announced a worldwide collaboration and option agreement directed to the discovery of up to 10 novel antibody-target pairs arising from three specified tumor types using Immunome’s Discovery Engine. Under the terms of the agreement, Immunome will grant AbbVie the option to purchase worldwide rights for up to 10 novel target-antibody pairs arising from the selected tumors. Immunome received an upfront payment of $30 million and will be eligible to receive additional platform access payments in the aggregate amount of up to $70 million based on AbbVie’s election for Immunome to continue research using its Discovery Engine. Immunome is also eligible to receive development and first commercial sale milestones of up to $120 million per target with respect to certain products derived from target-antibody pairs that AbbVie elects to purchase, with potential for further sales-based milestones as well as tiered royalties on global sales.

In February, AbbVie and Capsida Biotherapeutics Inc. announced an expanded strategic collaboration to develop genetic medicines for eye diseases with high unmet need. AbbVie’s extensive capabilities will be paired with Capsida’s novel adeno-associated virus (AAV) engineering platform and manufacturing capability to identify and advance three programs. The collaboration builds upon the neurodegenerative disease partnership announced in 2021.

Under the terms of the expanded agreement, Capsida will receive $70 million, consisting of upfront payments and a potential equity investment. For the three programs, Capsida may be eligible to receive up to $595 million in option fees and research and development milestones, with potential for further commercial milestones. Capsida is also eligible to receive mid-to-high single-digit royalty payments on future product sales. Capsida will lead capsid discovery efforts for all programs using its high throughput AAV engineering platform and will be responsible for process development and early clinical manufacturing. AbbVie will lead innovative therapeutic cargo approaches and be responsible for development and commercialization.

In July, AbbVie and Calibr announced an expanded strategic collaboration to advance several innovative preclinical and early-stage clinical assets across AbbVie’s core therapeutic growth areas including immunology, oncology, neuroscience, and other areas of interest. This partnership is an expansion of the collaboration AbbVie and Scripps Research formed in 2019 to develop a broad range of potential new and novel therapeutics. In addition to programs initially named in the collaboration from preclinical to IND stages of development, Calibr will present to AbbVie a certain number of new discovery targets and preclinical assets of mutual interest for option considerations.

Under the terms of the agreement, AbbVie will provide Calibr with research option payments over the course of five years to obtain a first-exclusive option to develop and commercialize candidates arising from the independent preclinical research conducted by Calibr, with the goal of advancing its pipeline of therapeutic programs. Upon AbbVie’s decision to exercise its option to a specific program, Calibr is eligible to receive additional payments from AbbVie, including option exercise fees, success-based development and commercial milestone payments, as well as tiered royalties.

Product performance

AbbVie’s autoimmune flagship Humira  placed second among all medicines by revenue in 2022, trailing only the Pfizer/BioNTech COVID vaccine, with sales of $21.24 billion, an improvement of 2.6 percent compared with 2021. In the United States, Humira sales increased 7 percent in 2022 primarily driven by market growth across all indications and favorable pricing. This increase was partially offset by a lower market share following the corresponding market share gains of Skyrizi and Rinvoq. Internationally, Humira revenue decreased 15 percent in 2022 primarily driven by direct biosimilar competition. On January 31, 2023, Humira lost exclusivity in the United States. In the first half of 2023, sales of Humira declined by 25.2 percent to $7.55 billion.

The largest bounce by any product in AbbVie’s portfolio in 2022 was enjoyed by Skyrizi, with sales of $5.17 billion and growth of 75.7 percent over the previous year. According to company leaders, this was driven by continued strong volume and market share uptake since launch as a treatment for plaque psoriasis as well as market growth. Sales were also favorably impacted by recent regulatory approvals and expansion of Skyrizi for the treatment of psoriatic arthritis and Crohn’s disease. In the first half of 2023, Skyrizi sales rose by another 47.9 percent to $3.24 billion.

In March, AbbVie announced positive top-line results from INSPIRE, a Phase III induction study, showing Skyrizi met the primary endpoint of clinical remission (per Adapted Mayo Score) at week 12, as well as all secondary endpoints in adult patients with moderately to severely active ulcerative colitis. In the study, 20.3 percent of patients receiving Skyrizi achieved clinical remission compared to 6.2 percent of patients receiving placebo. The INSPIRE study enrolled patients that demonstrated intolerance or inadequate response to conventional therapies and/or advanced therapies (biologics, JAK inhibitors and S1P receptor modulators). A significantly greater proportion of patients treated with Skyrizi achieved endoscopic improvement at week 12 compared to placebo (36.5 percent versus 12.1 percent). Furthermore, 24.5 percent of patients treated with Skyrizi achieved histologic-endoscopic mucosal improvement at week 12 versus 7.7 percent of those receiving placebo.

Also in March, AbbVie announced new 52-week data from an open-label, single-arm study demonstrating improved plaque psoriasis signs and symptoms among a difficult-to-treat patient population who received Skyrizi. These moderate-to-severe plaque psoriasis patients previously had a suboptimal response to treatment with secukinumab or ixekizumab, both IL-17A inhibitor therapies, for at least six months before switching to Skyrizi.

Findings from this Phase IIIb, open-label single-arm study showed that 56.3 percent of patients who received Skyrizi, without a washout period following a suboptimal response to secukinumab or ixekizumab achieved the week 16 primary endpoint of reduced signs and symptoms of psoriasis (sPGA 0/1). A suboptimal response was defined as a static Physician’s Global Assessment (sPGA) score of 2 or 3 and body surface area of 3 percent to <10 percent after at least six months of treatment with secukinumab or ixekizumab. The mean duration of treatment was 2.6 years for patients receiving secukinumab, and 2.1 years for patients receiving ixekizumab.

In June, AbbVie announced positive top-line results from COMMAND, its Phase III maintenance study, showing Skyrizi achieved the primary endpoint of clinical remission (per Adapted Mayo Score) at week 52, as well as key secondary endpoints in adult patients with moderately to severely active ulcerative colitis. In COMMAND, 51 percent of patients treated with Skyrizi 180 mg and 48 percent of patients treated with Skyrizi 360 mg achieved endoscopic improvement at week 52 versus 32 percent of patients in the induction-only control group. Additionally, significantly more patients treated with Skyrizi 180 mg and 360 mg achieved histologic endoscopic mucosal improvement at week 52 compared to those treated with induction only: 43 percent and 42 percent, respectively, versus 23 percent. A significantly higher proportion of patients who received Skyrizi 180 mg or 360 mg achieved steroid-free clinical remission compared to the induction-
only control group at week 52 (40 percent and 37 percent, respectively, versus 25 percent).

In July, AbbVie announced results from the head-to-head Phase IV IMMpulse study that evaluated the efficacy and safety of Skyrizi compared to Otezla among adult patients with moderate plaque psoriasis eligible for systemic therapy. This study achieved all primary and ranked secondary endpoints with no new safety signals identified.

At Week 16, a significantly higher proportion of patients who received Skyrizi achieved the Period A co-primary endpoints of Psoriasis Area and Severity Index (PASI) 90 and Static Physician’s Global Assessment (sPGA) 0/1 (55.9 percent of patients achieved PASI 90 and 75.4 percent achieved sPGA 0/1 with Skyrizi versus 5.1 percent and 18.4 percent with Otezla). The proportion of patients achieving the ranked secondary endpoint of PASI 75 at Week 16 was also significantly higher in Skyrizi- versus Otezla-treated patients (84.7 percent versus 18.8 percent).

At Week 52, among patients who failed to achieve PASI 75 after 16 weeks of treatment with Otezla, a significantly higher proportion of patients re-randomized to treatment with Skyrizi achieved the Period B primary endpoint of PASI 90 as compared to those reassigned to continue treatment with Otezla (72.3 percent versus 2.6 percent. After 52 weeks of continuous treatment, 73.7  percent of Skyrizi patients achieved the pre-specified endpoints of PASI 90 and 63.6 percent PASI 100, with 4.5 percent and 2.7 percent of Otezla patients achieving PASI 90 and PASI 100 at Week 52, respectively.

In August, AbbVie submitted applications for a new indication to FDA and EMA for Skyrizi for the treatment of adult patients with moderately to severely active ulcerative colitis. The applications were supported by data from two Phase III clinical trials: an induction study, INSPIRE, and a maintenance study, COMMAND. Significantly more patients treated with Skyrizi 1200 mg IV at week 12 in the induction study and 180 mg or 360 mg SC at week 52 in the maintenance study achieved the primary endpoint of clinical remission (per Adapted Mayo Score), compared to patients receiving placebo. Additionally, more Skyrizi-treated patients in both the induction and maintenance studies achieved the key secondary endpoints of endoscopic improvement (endoscopic subscore ≤1 without evidence of friability) and histologic endoscopic mucosal improvement (HEMI, defined as endoscopic subscore ≤1 without evidence of friability and Geboes score ≤3.1) compared to placebo.

In September, AbbVie announced top-line results from the Phase III SEQUENCE clinical trial evaluating Skyrizi 600 mg intravenous induction at week 0, 4, and 8, and 360 mg subcutaneous injection starting at week 12 and every 8 weeks thereafter), versus ustekinumab (Stelara, IV dose at week 0 and 90 mg SC every 8 weeks thereafter) through week 48 in patients with moderately to severely active Crohn’s disease who have failed one or more anti-TNFs. The results of the first primary endpoint, clinical remission (per Crohn’s Disease Activity Index) [CDAI], defined as CDAI <150) at week 24, met non-inferiority of Skyrizi versus Stelara (non-inferiority margin of 10 percent); remission rates were 59 percent in the Skyrizi group and 40 percent in the Stelara group. The results of the second primary endpoint, endoscopic remission (SES-CD ≤4 and at least a 2-point reduction versus baseline and no sub-score greater than 1 in any individual component) at week 48 met superiority of Skyrizi versus Stelara; remission rates were 32 percent in the Skyrizi group and 16 percent in the Stelara group.

Sales of the oncologic Imbruvica were $4.57 billion in 2022, a decline of 15.5 percent. Company leaders say this was as a result of decreased market demand and lower market share in the United States. The decrease was also partially offset by increased collaboration revenue. In the first half of 2023, Imbruvica sales fell another 23 percent to $1.79 billion.

In April, AbbVie announced its intent to voluntarily withdraw, in the United States, accelerated Imbruvica approvals for patients with the blood cancers mantle cell lymphoma (MCL) who have received at least one prior therapy and with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy. This voluntary action was due to requirements related to the accelerated approval status granted by FDA for MCL and MZL. These indications were approved via this pathway based on overall response rates in Phase II clinical studies. To confirm clinical benefit following accelerated approvals, additional studies are required by FDA.

Both of AbbVie’s Botox franchises, Therapeutic and Cosmetic, enjoyed solid growth in 2022, with Therapeutic up 10.9 percent to $2.72 billion and Cosmetic rising 17.2 percent to $2.62 billion. Cosmetic’s growth came due to sustained consumer demand in the United States, which was moderated in the second half of the year by economic pressures impacting consumer discretionary spending, and increased investment in key international markets. Therapeutic’s growth, company leaders say, was due to market growth. In the first half of 2023 sales of Botox Therapeutic rose another 13.5 percent to $1.47 billion while Botox Cosmetic edged up another 0.6 percent to $1.34 billion.

AbbVie’s second up-and-coming autoimmune drug, Rinvoq, generated $2.52 billion in sales for the company, an improvement of 52.8 percent over the previous year. Company executives say this was primarily driven by continued strong volume and market share uptake since launch for the treatment of moderate-to-severe rheumatoid arthritis as well as market growth. Revenue was also favorably impacted by recent regulatory approvals and expansion of Rinvoq for the treatment of psoriatic arthritis, atopic dermatitis, ankylosing spondylitis, ulcerative colitis, and non-radiographic axial spondyloarthritis. In the first half of 2023, sales of Rinvoq rose another 51.8 percent to $1.6 billion.

In March, AbbVie announced topline results from a Phase II study of Rinvoq given alone or as combination therapy (ABBV-599) with a Bruton’s tyrosine kinase inhibitor (elsubrutinib, 60 mg), once daily in patients with moderately to severely active systemic lupus erythematosus (SLE). The SLEek study met the primary endpoint of SLE Responder Index (SRI-4) and steroid dose less than or equal to 10 mg prednisone equivalent once per day at week 24 in the upadacitinib 30 mg group. Based on the results, AbbVie is advancing its clinical program of Rinvoq in SLE to Phase III.

In May, FDA approved Rinvoq for the treatment of adults with moderately to severely active Crohn’s disease who have had an inadequate response or intolerance to one or more TNF blockers. This was the seventh FDA approval for Rinvoq across rheumatology, dermatology, and gastroenterology, where it is now indicated in both ulcerative colitis and Crohn’s disease. The European Commission had approved Rinvoq for a similar indication the month before.

FDA’s approval was supported by data from two induction studies, U-EXCEED and U-EXCEL, and the U-ENDURE maintenance study. Statistical significance was achieved for the co-primary endpoints and key secondary endpoints with Rinvoq 45 mg in the induction studies and Rinvoq 15 mg and 30 mg in the maintenance study compared to placebo.

In the two induction studies, 34 percent and 46 percent of patients treated with Rinvoq 45 mg achieved endoscopic response (defined as a decrease of greater than 50 percent from the baseline Simplified Endoscopic Score for CD [SES-CD] or for patients with isolated ileal disease and a baseline SES-CD of 4, at least a 2-point reduction from baseline) at week 12, respectively, compared to 3 percent and 13 percent of patients receiving placebo. In the maintenance study, 28 percent and 41 percent of patients treated with Rinvoq 15 mg and 30 mg achieved endoscopic response at week 52, respectively, compared to 7 percent of patients receiving placebo.

In July, AbbVie announced that the first patient had been dosed in the Phase III Step-Up HS study evaluating Rinvoq in adults and adolescents with moderate-to-severe hidradenitis suppurativa (HS) who have failed anti-tumor necrosis factor (TNF) therapy and/or one approved non-anti-TNF inhibitor therapy for HS. The study’s primary endpoint will measure the percentage of participants achieving HS clinical response (HiSCR) 50, defined as at least a 50 percent reduction in the total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to baseline at week 16.

The atypical antipsychotic Vraylar generated $2.04 billion in sales for AbbVie in 2022, up 17.9 percent from the previous year. Company leaders credited this to higher market share and market growth. In the first half of 2023 sales of Vraylar rose another 32.6 percent to $1.22 billion.

Venclexta, for several forms of leukemia, brought in $2.01 billion in sales to AbbVie in 2022, an improvement of 10.4 percent. Company leaders credited this to continued expansion of Venclexta for the treatment of patients with CLL and acute myeloid leukemia. In the first half of 2023, sales of Venclexta rose another 13.4 percent to $1.11 billion.

In June, AbbVie announced new findings demonstrating sustained long-term safety and efficacy of Venclyxto/Venclexta-based combination therapies in patients with previously untreated CLL with co-existing conditions, as well as R/R CLL. New six-year follow-up results from the Phase III CLL14 study showcase updated outcomes in previously untreated patients with CLL and co-existing conditions. Patients treated with fixed-duration Venclyxto plus obinutuzumab continued to experience improved PFS and higher rates of undetectable minimal residual disease (uMRD) when treated with fixed-duration Venclyxto plus obinutuzumab compared to those who received chlorambucil plus obinutuzumab (53.1 percent versus 21.7 percent, respectively).

The data also showed significantly improved rates of time to next treatment (TTNT) with Venclyxto plus obinutuzumab at 65.2 percent compared to chlorambucil plus obinutuzumab at 37.1 percent. The observed differences in PFS and TTNT benefits between venetoclax-based treatment and chemoimmunotherapy were maintained across all risk groups, including patients with high-risk molecular features of CLL.

Final data from the Phase III MURANO trial showcase that R/R CLL patients treated with two-year fixed-duration Venclyxto plus rituximab sustained significantly longer median PFS at 54.7 months, the study’s primary endpoint, compared to 17.0 months with bendamustine plus rituximab after seven years of median follow-up.

Seven-year OS rates were 69.6 percent for patients treated with the Venclyxto-based combination versus 51 percent for study participants who received bendamustine-based combination. Furthermore, most of the patients treated with the full two-year venetoclax-based combination achieved uMRD (70.3 percent) at the end of their treatment course, and those patients were shown to have improved PFS and OS compared to patients with detectable MRD (29.7 percent).

The migraine treatment Ubrelvy enjoyed sales of $680 million in 2022, up 23.2 percent compared with 2021. Company leaders say this was primarily due to increased market share uptake since launch, partially offset by unfavorable pricing. In the first half of 2023 sales of Ubrelvy were up another 7.7 percent to $348 million.

In the pipeline

In March, AbbVie received a Complete Response Letter from FDA for the New Drug Application for ABBV-951 (foscarbidopa/foslevodopa) for the treatment of motor fluctuations in adults with advanced Parkinson’s disease. In its letter, FDA requested additional information about the device (pump) as part of the NDA review. The CRL does not request that AbbVie conduct additional efficacy and safety trials related to the drug. AbbVie plans to resubmit the NDA as soon as possible.

In April, FDA approved expanding the indication of Qulipta for the preventive treatment of migraine in adults. The approval made Qulipta the first and only oral calcitonin gene-related peptide (CGRP) receptor antagonist approved to prevent episodic and chronic migraine. The European Commission approved Qulipta, under the brand name Aquipta, for a similar indication in August.

Qulipta’s expanded chronic migraine indication is based on the pivotal Phase III PROGRESS trial evaluating Qulipta 60 mg once daily in adult patients with chronic migraine, which met its primary endpoint of statistically significant reduction from baseline in mean monthly migraine days compared to placebo across the 12-week treatment period. The average monthly migraine days (MMDs) for patients at baseline during the clinical trial was 19.3 The trial also demonstrated that treatment with Qulipta resulted in statistically significant improvements in all six secondary endpoints. This includes key secondary endpoints that measured the proportion of patients that achieved at least a 50 percent reduction in mean monthly migraine days across the 12-week treatment period and improvements in function and reduction in activity impairment due to migraine.

That same month, AbbVie announced positive data from its Phase III ELEVATE study, evaluating Qulipta for the preventive treatment of episodic migraine in people who had previously failed two to four classes of oral preventive medications. The results of the study demonstrated adult patients in the Qulipta 60 mg once daily (QD) arm experienced a decrease of 4.20 days in their mean monthly migraine days (MMDs) across the 12-week treatment period, which was statistically significantly greater than the 1.85 day reduction observed in the placebo arm.

In May, FDA approved Epkinly (epcoritamab-bysp), as the first and only T-cell engaging bispecific antibody for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B–cell lymphoma (HGBL), after two or more lines of systemic therapies. Epkinly was approved under FDA’s Accelerated Approval program based on response rate and durability of response. The medicine is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration.

In the expansion cohort of the EPCORE NHL-1 trial of Epkinly, 148 patients with CD20+ DLBCL were enrolled, 86 percent of which were diagnosed with DLBCL NOS, including 27 percent with DLBCL transformed from indolent lymphoma, and 14 percent with HGBL. The median number of prior therapies was three (range: 2 to 11), with 30 percent receiving two prior therapies, 30 percent receiving three prior therapies, and 40 percent receiving four or more prior therapies. Eighteen percent had prior autologous hematopoietic stem cell transplantation, and 39 percent had prior chimeric antigen receptor (CAR)T-cell therapy. Eighty-two percent of patients had disease refractory to last therapy and 29 percent of patients were refractory to CAR T-cell therapy. Epkinly delivered an overall response rate of 61 percent, a complete response rate of 38 percent, and median duration of response of 15.6 months in heavily pretreated R/R DLBCL patients