Earnings Call Transcript
AbbVie Inc. (ABBV)
Earnings Call Transcript - ABBV Q4 2021
Operator, Operator
Good morning, and thanks for joining us. Also on the call with me today are Rick Gonzalez, Chairman of the Board and Chief Executive Officer; Michael Severino, Vice Chairman and President; Rob Michael, Vice Chairman, Finance and Commercial Operations and Chief Financial Officer; and Jeff Stewart, Executive Vice President, Chief Commercial Officer. Joining us for the Q&A portion of the call is Laura Schumacher, Vice Chairman, External Affairs, Chief Legal Officer, and Corporate Secretary. Before we get started, some statements we make today may be considered forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. 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. Additional information about these risks and uncertainties is included in our SEC filings. AbbVie undertakes no obligation to update these forward-looking statements except as required by law. On today’s conference call non-GAAP financial measures will be used to help investors understand AbbVie’s business performance. These non-GAAP financial measures are reconciled with comparable GAAP financial measures in our earnings release and regulatory filings from today which can be found on our website. Unless otherwise noted, our commentary on sales growth is on a comparable basis, which includes full current year and historical results for Allergan. For this comparison of underlying performance, all historically reported Allergan revenues have been recast to conform to AbbVie’s revenue recognition accounting policies, and exclude the divestitures of Zenpep and Viokace. References to operational growth further exclude the impact of exchange. Following our prepared remarks, we’ll take your questions. So with that, I’ll now turn the call over to Rick.
Rick Gonzalez, CEO
Thank you, Liz. Good morning, everyone. And thank you for joining us today. I’ll provide perspective on our overall performance and outlook, and then Jeff, Mike and Rob will review our quarterly business highlights, pipeline progress, financial results and guidance for 2022 in more detail. Our performances this quarter tops off another excellent year for AbbVie with results well above our initial expectations. We delivered full year 2021 adjusted earnings per share of $12.70, representing growth of more than 20% versus the prior year. Full-year adjusted net revenues were more than $56 billion, up 10.5% on a comparable operational basis. These results demonstrate balanced performance across each of our major growth franchises, including double-digit comparable operational revenue growth from immunology, aesthetics, and neuroscience. I’m extremely pleased with our momentum, and we’ve entered this year in a strong position, which is reflected in our guidance. We anticipate 2022 adjusted earnings per share of $14 to $14.20, representing growth of 11% at the midpoint. Longer-term, we remain well positioned with an impressive set of diversified growth assets. In immunology, Skyrizi and Rinvoq are already contributing meaningful revenue, including $4.6 billion in combined sales last year with substantial growth anticipated in 2022 and beyond. Over the next few months, we expect to add several new indications to the list of approved uses for these two assets, at which point, Skyrizi and Rinvoq will be commercialized across all of Humira’s major indications, plus atopic dermatitis. With the strong performance that we’re seeing in their initial indications and the robust data we’ve demonstrated across our broad development programs, we expect combined peak sales for Skyrizi and Rinvoq to exceed the peak revenues achieved by Humira. In hematological oncology, we’ve established a leading position with Imbruvica and Venclexta, which were both expected to remain important revenue contributors through the decade. To support our next wave of growth, we also have an exciting and diverse pipeline of promising new therapies to address critical unmet needs in both blood cancers and solid tumors. Notable opportunities from our mid to late stage oncology pipeline include Navitoclax for myelofibrosis, which has the potential to provide disease modification in a market where current treatments only address symptoms. At Epcoritamab, a potentially best-in-class CD3XCD20 for B-cell malignancies, including DLBCL and follicular lymphoma; ABBV-383, our BCMA CD3 bispecific, which has the potential to become a best-in-class treatment in multiple myeloma; and Teliso-V, our promising c-Met ADC being studied for nonsquamous non-small cell lung cancer, which was recently granted breakthrough therapy designation. In neuroscience, we have a portfolio of compelling and differentiated therapies to support robust long-term growth in migraine, Parkinson’s disease and psychiatric conditions. Ubrelvy and Qulipta are both demonstrating strong launch trajectories in migraine, with each treatment expected to contribute more than $1 billion in peak sales. Vraylar continues to have a significant opportunity with currently approved indications with peak sales expected to approach $4 billion. An approval in major depressive disorder represents upside to our current projections. And 951, a potentially transformative improvement to our current treatment options for patients with advanced Parkinson’s disease with peak sales also anticipated to be more than $1 billion. Our leading aesthetics portfolio represents another extremely attractive growth opportunity. This business is performing well above expectations, delivering full year 2021 sales of more than $5.2 billion, $700 million higher than our initial guidance. AbbVie’s increased promotional investments are driving accelerated category growth, especially in toxins and fillers, where there is substantial room for additional market penetration globally. Dedicated resources are also focused on delivering new product innovation within aesthetics, with several exciting R&D programs internally, including both short-acting and long-acting toxins, as well as novel fillers with biostimulatory or regenerative features. And we remain active with business development to pursue promising external technologies and complementary opportunities, including the recently closed Soliton acquisition, which further expands our body contouring portfolio. Given this focus and investment, we expect our aesthetics franchise to deliver high single digit revenue growth through the end of the decade, including sales of more than $9 billion in 2029. Lastly, we’ve developed a robust pipeline, including numerous attractive late-stage programs, novel early stage therapies in a growing range of potential platform technologies, which we expect will collectively contribute to our growth through the decade. With the actions that we’ve taken to diversify our sources of growth, we remain very confident in the long-term outlook for our business. Following the U.S. Humira LOE event in 2023, we expect to quickly return to growth in 2024 and deliver high-single-digit growth from 2025 to the end of the decade. This is a testament to the strength of AbbVie’s broad and balanced portfolio. In summary, this is an exciting time for our Company. We’re demonstrating excellent execution across our portfolio, and our long-term growth prospects remain very strong. With that, I’ll turn the call over to Jeff.
Jeff Stewart, CFO
Thank you, Rick. Looking at our quarterly results, we continue to demonstrate excellent commercial execution across our therapeutic portfolio. I’ll start with immunology, which delivered global revenues of more than $6.7 billion, reflecting growth of 13.3% on an operational basis. Global Humira sales were $5.3 billion, up 3.5%, with 6% revenue growth in the U.S. offset by biosimilar competition across the international markets, where revenues were down 8.8% on an operational basis. Skyrizi is performing extremely well. Global sales of nearly $900 million were up 12.4% on a sequential basis, reflecting continued market share gains. Skyrizi has now surpassed Humira as the leader for total prescriptions in the U.S. psoriasis biological market, with share of approximately 20%. We are also now leading the market in several international geographies, including Japan. Total in-place share, which includes both new and switching patients, remains very strong and now reflects roughly 37% patient share in the U.S. as well as leadership in nearly 20 key countries around the world. Skyrizi is also now approved for its second major indication, to treat adults with active psoriatic arthritis, further enhancing its compelling profile in dermatology. Field promotion is now active globally and early feedback from physicians has been very positive. Given Skyrizi’s demonstrated skin clearance and joint efficacy in our PSA clinical program, with nearly 30% of patients visiting dermatologists, having both skin and joint involvement, this new approval will sustain Skyrizi’s strong momentum. In addition, we are preparing for the launch of Skyrizi in Crohn’s disease, an indication with very meaningful long-term revenue potential, with regulatory approvals in both the U.S. and Europe anticipated this year. Rinvoq also continues to demonstrate robust growth. Global sales of more than $500 million were up 14% on a sequential basis. Prescriptions in RA remain strong with a total market share of more than 5.5% in the U.S. and nearly 5% across key international markets. We’re very pleased with the competitive labels for both PSA and atopic dermatitis, where we are making excellent progress with their launches globally. In atopic dermatitis, dermatologists appreciate key elements of Rinvoq’s new label, including the incorporation of stringent skin and itch endpoints, reflective of the performance in our registrational trials, as well as an adolescent indication and dosing flexibility. Managed care access is expected to ramp fairly quickly for both atopic dermatitis and PSA in the U.S. We are also preparing for the launches of Rinvoq in ulcerative colitis and axial SpA with regulatory approvals for both indications anticipated this year as well. Overall, we continue to feel very good about the performance and progress we’re making with both Rinvoq and Skyrizi, which are expected to contribute more than $15 billion in combined risk adjusted global sales in 2025. In hematologic oncology, global revenues were nearly $1.9 billion, up 4.7% on an operational basis. Venclexta once again delivered robust growth. Sales were up 34% on an operational basis with strong share performance across all approved indications. Imbruvica global revenues were down 2.7%, reflecting a slower than anticipated market recovery in CLL and increased share pressure from newer therapies. In neuroscience, revenues were more than $1.6 billion, up 19% on an operational basis, including robust double-digit growth for both Vraylar and Botox Therapeutic. I’m also very pleased with our performance in migraine, where we have a portfolio of multiple distinct therapies to address the full spectrum of this disease. This includes our two leading oral CGRP therapies. Ubrelvy for acute migraine, which delivered total sales of $183 million, up 13% on a sequential basis, and we anticipate robust sales growth again this year based on Ubrelvy’s competitive profile, continued strong new patient starts and a rapidly expanding CGRP segment. We also have Qulipta, the only oral CGRP treatment specifically developed for the prevention of episodic migraine. The launch is going extremely well. When considering both paid and bridge volume, Qulipta is already capturing nearly 20% of the new-to-brand share in the preventative CGRP class. Roughly three months post-launch, this is an incredible accomplishment and it’s a testament to Qulipta’s demonstrated efficacy, including rapid and meaningful reduction in migraine days. We expect commercial access for Qulipta to ramp quickly in the first half of this year. In eye care, revenues of $960 million were up 3.9% on an operational basis, including $364 million in sales from Restasis. Lastly, Mavyret were $427 million, down 10.1% on an operational basis, as treated patient volumes remained suppressed compared to pre-COVID levels. Overall, I’m very pleased with the performance and the momentum across the therapeutic portfolio. And with that, I’ll turn the call over to Mike for additional comments on our R&D programs.
Michael Severino, President
Thank you, Jeff. We made significant advancements across all stages of our pipeline in 2021, and we expect continued progress again this year. In immunology, we had several recent important regulatory updates. We implemented safety and indication updates to our RA label for Rinvoq and also received FDA approval in psoriatic arthritis and atopic dermatitis to create strong labels that highlight Rinvoq’s favorable benefit risk profile in both new indications. In atopic dermatitis, we received approval for both the 15 milligram and 30 milligram doses, and based on the impressive levels of skin clearance and itch reduction demonstrated in our development program, we believe Rinvoq will be an important new treatment option for adult and adolescent patients with moderate to severe atopic dermatitis, who have not responded well to other systemic agents, such as cyclosporine, methotrexate, azathioprine, or biologics. We also have regulatory applications under review for Rinvoq in ulcerative colitis, ankylosing spondylitis, and non-radiographic axial SpA. We expect an FDA approval decision next month for ulcerative colitis, in the second quarter for ankylosing spondylitis, and in the fourth quarter for non-radiographic axial SpA. In Europe, we anticipate approval decisions for ulcerative colitis and non-radiographic axial SpA in the second half of the year. We’re nearing completion of Rinvoq’s registrational program in Crohn’s disease, which is the last major indication expansion program for Rinvoq. We recently announced positive top-line results from the first phase 3 Crohn’s induction study, where Rinvoq demonstrated a significant impact on clinical remission and endoscopic response in a difficult-to-treat refractory patient population. We expect to see results from the second phase 3 Crohn’s induction study and from the maintenance study in the first half of this year with regulatory submissions anticipated in the second half of 2022. Also in immunology, we recently received FDA approval for Skyrizi in psoriatic arthritis, an important indication expansion for this asset. Based on the strong joint efficacy and the high level of skin clearance that Skyrizi provided in our registrational trials, we believe Skyrizi will be very competitively positioned as an effective new treatment option for psoriatic arthritis patients. We also have regulatory applications under review for Skyrizi in Crohn’s disease with approval decisions expected in the U.S. next month and in Europe, later this year. We’ve seen impressive results in our Crohn’s disease program, and we believe Skyrizi has the potential to become an important new therapy in this market, where there continues to be considerable unmet need. We’re making very good progress with our early-stage immunology pipeline as well, where we are developing novel agents with the goal of significantly advancing the standard-of-care across our core areas by providing deeper and more durable responses. Our anti-TNF steroid ADC ABBV-154 is a novel approach for delivering a potent steroid that has the potential to provide durable remission in diseases such as RA, PMR and Crohn’s disease. We expect to see preliminary data from our phase 2 dose ranging study in RA in the fourth quarter of this year. We also expect to see phase 2 proof-of-concept data in PMR and Crohn’s disease in 2023. In dermatology, our early-stage efforts are focused on developing oral agents that can provide clear skin with durable responses. Our RoRγT inverse agonist, ABBV-157 is designed to more effectively inhibit IL-17 production compared to pure antagonists, which has the potential to result in a greater impact on skin inflammation. We’ve recently begun a phase 2 dose-ranging study for ABBV-157 in psoriasis. Moving to oncology, where we continue to make good progress across all stages of our pipeline. We recently received an FDA breakthrough therapy designation for Teliso-V in the second line plus advanced or metastatic nonsquamous, non-small cell lung cancer based on the encouraging results we’ve seen to-date in our clinical program. Treatment options for patients who have exhausted platinum-based chemotherapy, immunotherapy, and targeted therapy are limited to single-agent chemotherapy, which typically provides response rates of only 15% to 20%, with a median overall survival of less than one year. Prognosis for these patients is very poor. While targeted therapies have been approved by the FDA for the 3% to 4% of non-small cell lung cancer patients harboring MET exon 14 skipping mutations, there are currently no therapies approved, specifically for the much larger group of patients who exhibit c-Met protein overexpression. Patients with overexpressed c-Met represents about 25% to 30% of the advanced or metastatic nonsquamous, non-small cell lung cancer population with wild-type EGFR, which corresponds to an incidence of approximately 35,000 patients each year in the U.S. In stage 1 of our phase 2 study, we saw promising efficacy in heavily pretreated patients who received Teliso-V, including a 54% objective response rate in those with highly expressed c-Met. The second stage of the phase 2 study is ongoing and has the potential to support an accelerated approval in second-line plus advanced metastatic nonsquamous non-small cell lung cancer. We expect to see additional data from this study next year. We also recently began the clinical program for our next-generation c-Met ADC, ABBV-400, which utilizes a more potent topoisomerase inhibitor payload to potentially drive deeper tumor responses in patients with both intermediate and high levels of c-Met expression. We also expect to see data this year from several important indication expansion programs for Venclexta, including results from the phase 3 CANOVA trial in relapsed/refractory multiple myeloma patients with a t(11;14) mutation as well as results from our program for Venclexta in previously untreated higher-risk MDS patients, where we received a breakthrough therapy designation. We plan to submit our regulatory applications to the FDA in the first half of this year for an accelerated approval in MDS and late in ‘22 or early ‘23 for multiple myeloma. Both indications represent important expansion opportunities for Venclexta and will help drive long-term growth for our oncology portfolio. We are also making very good progress with Epcoritamab, where we continue to generate strong data in early-stage studies to support our view that Epcoritamab has the potential to become a differentiated and best-in-class CD3xCD20 bispecific across several B-cell malignancies including diffuse B cell and follicular lymphomas. We’ll see monotherapy data in the third quarter from the phase 2 expansion cohort in DLBCL, which has the potential to support a submission for accelerated approval in the second half of this year. We also have a phase 3 study ongoing in third-line relapsed/refractory DLBCL and we plan to initiate several additional phase 3 trials this year, including studies in earlier lines of therapy for diffuse B-cell lymphoma in multiple combinations, as well as in follicular lymphoma in combination with rituximab and Revlimid. This year, we’ll also see additional data maturing from our cohort expansion studies for ABBV-383, both as a monotherapy and in combination with standard-of-care and novel agents in multiple myeloma. We believe our BCMA-CD3 bispecific has the potential to be differentiated on efficacy, safety, and dosing interval and can be best-in-class across multiple lines of therapy. We plan to initiate phase 3 studies later this year in relapsed/refractory multiple myeloma. We also continue to make good progress with Navitoclax in myelofibrosis, where we’ve seen strong mid-stage data supporting our view that Navitoclax has the potential to provide disease modification, which we believe will lead to improved and durable clinical outcomes for patients. We expect a phase 3 data readout and regulatory submissions in the first half of next year, with approval anticipated near the end of 2023. Moving to neuroscience, where we expect several important pipeline events in 2022 as well. We recently completed discussions with the FDA and are preparing to submit our application for Vraylar as an adjunctive treatment for major depressive disorder. Based on the totality of the data and the strong benefit-risk profile demonstrated in our clinical program, we believe Vraylar has the potential to be competitively positioned as an adjunctive treatment for major depressive disorder. We expect a submission in the first quarter and an approval decision by the end of the year. We’ve also completed our registration-enabling program for ABBV-951, our novel subcutaneous levodopa/carbidopa delivery system for treatment of advanced Parkinson’s disease. In our phase 3 studies, 951 proved superior to oral levodopa/carbidopa in reducing motor fluctuations in this advanced population, and we believe our innovative new delivery system represents a potentially transformative improvement to current treatment options. We remain on track to submit our regulatory applications in the first half of this year in the U.S. and Europe, with both approval decisions anticipated in early 2023. And we expect to see phase 3 data for Qulipta in chronic migraine prevention later in the first quarter and plan to submit our regulatory applications in both the U.S. and Europe this summer, with approval decisions expected in the first half of 2023. So, in summary, we remain focused on continuing to execute on our pipeline programs and anticipate numerous important regulatory and clinical milestones across all stages of our pipeline in 2022. This includes important indication expansion for on-market drugs and data readouts and regulatory actions for key late-stage assets as well as proof-of-concept data from several early-stage NME programs. With that, I’ll turn the call over to Rob for additional comments on our fourth quarter performance and our 2022 financial outlook.
Rob Michael, CFO
Thank you, Mike. AbbVie once again delivered outstanding performance while also advancing our strategic priorities. The strong results across our portfolio continue to support AbbVie’s long-term growth outlook. Starting with fourth quarter results. We reported adjusted earnings per share of $3.31, up 13.4% compared to the prior year and $0.05 above our guidance midpoint. Total adjusted net revenues were $14.9 billion, up 7.5% on an operational basis, excluding a 0.1% unfavorable impact from foreign exchange. The adjusted operating margin ratio was 49.3% of sales, an improvement of 240 basis points versus the prior year. This includes adjusted gross margin of 83.6% of sales, adjusted R&D investment of 12.1% of sales, and adjusted SG&A expense of 22.2% of sales. Net interest expense was $571 million, and the adjusted tax rate was 12.5%. Shifting to 2022, our full year adjusted earnings per share guidance is between $14 and $14.20, reflecting growth of 11% at the midpoint. Excluded from this guidance is $4.74 of known intangible amortization and specified items. We expect adjusted net revenue of approximately $60 billion. At current rates, we expect foreign exchange to have a 0.8% unfavorable impact on full year sales growth. This revenue forecast comprehends the following approximate assumptions for our key products and therapeutic areas. We expect Immunology global sales to grow double digits, including U.S. Humira growth of 8%, International Humira revenue of $2.6 billion at current exchange rates, Skyrizi global sales of $4.4 billion and Rinvoq global sales of $2.7 billion. In hematologic oncology, we expect Venclexta global sales of $2.3 billion and Imbruvica global revenue of $5.4 billion. The Imbruvica forecast assumes market recovery in CLL, offset by share erosion from increased competition. For aesthetics, we expect global sales of $5.9 billion, including $2.6 billion for Botox Cosmetic and $1.7 billion from Juvederm. For neuroscience, we expect global revenue of $6.9 billion, including Botox Therapeutic sales of $2.7 billion, Vraylar sales of $2.2 billion, Ubrelvy sales of $800 million and Qulipta sales of $200 million with commercial access increasing rapidly in the first half of the year. For eye care, we expect global sales of $2.9 billion, including $700 million from Restasis, which assumes no generic competition in the first half of 2022. Lastly, we expect Mavyret global revenue of $1.7 billion. Looking at the P&L for 2022, we are forecasting full year adjusted gross margin of approximately 84% of sales, adjusted R&D investment of approximately $6.8 billion and adjusted SG&A expense of approximately $12.7 billion. This guidance includes approximately $2.5 billion in expense synergies from the Allergan acquisition. We are forecasting the adjusted operating margin ratio to expand by 120 basis points to approximately 51.5% of sales. We expect adjusted net interest expense approaching $2.2 billion, our non-GAAP tax rate to be approximately 12.7% and our share count to be roughly flat to 2021. Turning to the first quarter, we anticipate net revenue approaching $13.5 billion. At current rates, we expect foreign exchange to have a 1.3% unfavorable impact on sales growth. This revenue forecast comprehends the following approximate assumptions for our key therapeutic areas: Immunology sales of $6.2 billion, HemOnc revenue of $1.7 billion, aesthetic sales of $1.3 billion, neuroscience revenue of $1.5 billion and eye care sales of $900 million. We are forecasting an adjusted operating margin ratio of approximately 51% of sales, and we model a non-GAAP tax rate of 12.4%. We expect adjusted earnings per share between $3.10 and $3.14, excluding approximately $1.22 of known intangible amortization and specified items. Finally, AbbVie’s strong business performance and outlook continue to support our capital allocation priorities. We expect to generate adjusted free cash flow of approximately $24 billion in 2022, which is net of roughly $1 billion in Skyrizi royalty payments. This cash flow will fully support a strong and growing dividend, which we have increased by more than 250% since inception; continued debt repayment, where we expect to pay down just above $12 billion of debt in 2022 and estimate a net leverage ratio of 1.8 times by the end of the year. Our strong cash flow also allows for continued business development, with approximately $2 billion allocated annually to augment our pipeline with the most promising external technologies and innovative therapies. In closing, we are very pleased to AbbVie’s strong results in 2021. And we expect to deliver robust performance in 2022 and over the long term. With that, I’ll turn the call back over to Liz.
Operator, Operator
Thanks, Rob. We will now open the call for questions. In the interest of hearing from as many analysts as possible over the remainder of the call, we ask that you please limit your questions to one or two. Operator, we’ll take the first question.
Operator, Operator
Thank you. Our first question comes from Chris Schott with JP Morgan.
Chris Schott, Analyst
Great. Thank you for the questions. I have a couple regarding Rinvoq in more detail. First, in rheumatoid arthritis, it seems like volumes have leveled off a bit. This likely isn’t surprising following the label revision, but could you provide more insight into the feedback from physicians? When do you expect to see sequential growth in that area again? My second question about Rinvoq pertains to atopic dermatitis. Can you elaborate on the ramp-up you anticipate here? Will this take time, or do you see potential quick wins, possibly due to some recent DP failures? Overall, I’m trying to understand the $2.7 billion guidance better: how much of that is from rheumatoid arthritis, and how much from new indications? I appreciate your insights. Thank you.
Jeff Stewart, CFO
Thanks. Hi, it’s Jeff. I’ll provide some insights on the RA situation. The RA market is progressing as we expected following the drug safety and label updates. I’ll mention our in-play share, which requires caution regarding overall market volumes in December and January. Before the Drug Safety Communication, our in-place share in RA was about 16%, closely following Humira, which is strong. In the fourth quarter, this share has decreased by approximately 20%, reporting 14% in October and just over 13% in November, aligning with our expectations. We see about a 20% shift in new-to-brand starts during this period, with the market maintaining stability, showing little change in second-line plus treatments, while doctors are starting to limit first-line starts according to the label. As promotional activities resume in the first quarter after December, we anticipate continued stability, evident in our overall share and weekly progress as we pivot towards second-line plus treatments. The market is responding similarly to our expectations for RA. Additionally, the PsA indication will enhance this RA dynamic, along with significant axial approvals anticipated later in the year. Overall, everything is moving forward as we had anticipated from a market standpoint. Regarding atopic dermatitis, we’re very satisfied with the label. It includes stringent endpoints like EASI 90 and high skin clearance, along with significant itch reduction. Both doses are approved, and the market has reacted positively to the adolescent indication, which is crucial. We expect to see a ramp-up in this area, and it won’t be slow. Regarding our ability to capture patients, it’s already happening, although we haven’t reported any TRxs yet. We can observe it in the market, particularly among dupi failures, which is to be expected. A notable number of patients after 4 or 5 years have exited the market and are likely to return. We are hearing from our research teams about partial responders to dupi who are not doing well, especially with itch, and we are seeing some early starts in that group. We are also seeing patient starts among those with significant skin involvement. The market appears to be developing as we anticipated. It’s anticipated that most initial starts in the second-line market will involve dupi partial responders or nonresponders, which represents a substantial population. We expect our access to ramp up quickly in the early part of the year, and we are optimistic. Now, I’ll turn it over to Rob for insights on the sales magnitude.
Rob Michael, CFO
Thanks, Jeff. Chris, this is Rob. So of the Rinvoq guidance of $2.7 billion, the AD and spine indications will each contribute a couple of hundred million dollars, while UC will contribute around $100 million. And to keep in mind in terms of sequential growth, keep in mind, in the U.S., you tend to see from Q4 to Q1, it’s a sequential decline. So that’s just a seasonal dynamic that we see across the business. So you would see sequential growth resume in Q2 and beyond.
Operator, Operator
Our next question comes from Ronny Gal from Bernstein.
Ronny Gal, Analyst
First question is around Humira. I was wondering if you guys will be in a position to give us some sort of a floor number in 2023 based on payer contracts. Sometimes this year, obviously, the market is looking for that. And then, when I talk to payers, it seems a lot of the decisions about what product they would use longer term will not happen in 2023. That will happen in 2024. You kind of talked about kind of like a decline and then a quick ramp-up. Do you see the floor here in 2023, or do you see it in 2024? And then, if I could sneak one more. You have one of the largest differences between GAAP and non-GAAP earnings in the industry because of that Allergan acquisition. As you look at the amortization period and so forth, when do you think this thing will begin to narrow in a significant way just because that’s a concern for some investors?
Rick Gonzalez, CEO
Okay, Ronny, this is Rick Gonzalez. I’ll take the Humira questions. I think if you look at the guidance we provided thus far, I mean, I think that’s consistent with how we see the market playing out overall. We’ve said basically you should be thinking about 45% erosion, plus or minus 10%, that’s probably a reasonable range. Nothing has really given us any indication that it should be different than that at this point. I think we will be in a position as we move later on this year to potentially be able to provide some more specificity around that. We should be through all of the contracting at that point, in a better position to be able to understand the ramp and the change that will occur over that period of time, and we certainly want to provide guidance when we have confidence that we can give you a high degree of specificity of what that guidance looks like. As it relates to your question about the floor for Humira, I think your question is, will the floor for Humira be in ‘23 or ‘24. And I believe you’ll see further erosion from ‘23 to ‘24 on the Humira business alone. But what we have described is we returned to growth on the overall business. So, you have to think about it from the perspective of this underlying growth engine that gets suppressed in ‘23 by the significant erosion that you see around Humira, both price and some volume. And then, as that continues, it continues at a slower pace when we get into ‘24. So, the overall business has the ability to be able to drive growth for the total Company. But yes, Humira would continue to decline in ‘24. And then Rob, why don’t you cover the third one?
Rob Michael, CFO
Sure, Ronny, this is Rob. When we look at our adjustments for specified intangible amortization, I'd estimate that intangible amortization accounts for about 70% of it, based on the $4.74 guidance provided for this year. This trend will persist, as these items decrease over several years. I believe this level will likely remain for the next few years. Another significant factor is the contingent consideration, which relates to purchase accounting, and that will definitely vary over time. Those are the two main components of this year's guidance. Additionally, integration costs are beginning to decrease, so we can expect those to lower further. Overall, I think you can anticipate modeling this level moving forward.
Operator, Operator
Our next question comes from Andrew Baum with Citi.
Andrew Baum, Analyst
A couple of questions. Firstly, on Imbruvica. As we move into 2022 and the COVID dynamic shakes out, we’ll be able to see the impact of competition versus COVID. Assuming that a significant chunk of the U.S. slowing growth rate or decline is due to competition, what can be done to recoup the momentum against the narrative, particularly of Calquence? And then second, in terms of your aesthetics business, you terminated your contract with Medytox liquid formulation. There are competitive products coming to market as well as increasing price competition. How much of that is concerned or is your franchise and the breadth of the portfolio enough to minimize any impact of novel formulations? Thank you.
Jeff Stewart, CFO
Yes. Hi, Andrew. It’s Jeff. So thanks. And you’re right that we still have the continuing lingering effect with COVID, and Rob addressed that in his comments. So, we still see the market versus ‘19 levels down about 10% and even marginally down from 2020 in Q4. So we anticipate that that will moderate going forward. And then we’re left to manage the competitive impact. So, we are seeing competitive BTKs have some impact on Imbruvica, but we’re also seeing the competitive impact from our own Venclexta. So we have to start to think about looking at the combination of the AbbVie position, which is still very, very strong. To give you some sense in second-line, we have 45% share of the market, and it’s even higher in third-line, and it’s in the 30s for frontline. So, we have to continue, which is our strategy to highlight where we have a lot of distinction, which is the strength of our data across every comparator in CLL, the overall survival benefit, and then also bring the strength of our overall portfolio. So, that’s how we plan to mitigate it. As Rob mentioned, we see market recovery offset by some share pressure on Imbruvica, mitigated by positive Ven impact. So, that’s how we see the market develop as we go into 2022. We also are seeing some pricing pressure in some select segments that are also contributing to the share loss for Imbruvica. And obviously, as much as we can, we keep the pricing discipline in the market moving forward. So, I hope that context helps.
Rick Gonzalez, CEO
Andrew, this is Rick. I’ll cover the Aesthetics questions for you. And certainly, as you look at Botox, both here in the U.S. and internationally, it competes today against a significant number of competitive alternatives that are available. I think it’s a pretty impressive position that Botox has in the market. When you look at the brand equity that it has, when you look at the confidence that injectors have in using the product, they tend to describe it as the most forgiving of all the toxins that they have experience with. And then there’s obviously a fairly significant customer loyalty aspect to Botox with the loyalty programs and Allergan has a very significant loyalty program that offers patients incentives to be able to use the product and to go back and get repeat procedures. Having said all of that, we feel confident in the position that we have competitively against the competitive alternatives that we see out there and those that we see coming. We have a very active R&D effort in the aesthetics R&D group now that’s looking at next-generation toxins. Two in particular that we highlighted in the comments earlier are we had a short-acting toxin that’s in development that’s progressing very nicely, and we have a true long-acting toxin that’s in development as well. And we believe that those will help grow the market. But if I look at the market now, obviously, we’ve seen significant acceleration in the market since we’ve activated many of the strategies that we put in place after acquiring Allergan. But if I look at our overall share, overall share has stayed very steady, in fact, might have ticked up one point in the latest set of data. So, that tells you that we’re not only growing the market very rapidly but we’re continuing to compete quite effectively against the alternatives that are out there. So, I’m not overly concerned about what I see on the horizon. I think we have the opportunity to build the market even larger with some of the next generation toxins that we’re working on when we bring those to the marketplace. So, I feel good about our position in toxins and in fillers as we move forward.
Operator, Operator
Our next question comes from Vamil Divan from Mizuho Securities.
Vamil Divan, Analyst
So, a couple. I always appreciate all the guidance. You guys gave both near term and longer term. Just a couple of questions I have related to more of the longer-term guidance you’ve given. In the past, you had talked about your HemOnc franchise sort of in peak sales or sales I guess in 2025 of around $13 billion. When you updated some of your numbers earlier last month, I don’t think you updated that one. So, I’m just curious if you still think that that’s a reasonable sort of 2025 expectation? And then, the other one is around Ubrelvy, where you’ve sort of stayed with this guidance of sort of more than $1 billion in peak sales. But you’re already guiding to $800 million of sales just in this current year, pretty early in the launch. So, I’m just wondering if you can maybe give a little better sense of how you’re viewing sort of the longer-term opportunity for Ubrelvy and maybe if you want to mention Qulipta, I know that’s early, but at least for Ubrelvy, do you think there’s significant upside to that $1 billion number you’ve mentioned before? Thank you.
Rick Gonzalez, CEO
Vamil, this is Rick. I’ll start with the first question and then Jeff will address the one about Ubrelvy. That’s a good question. The HemOnc market, especially in areas like CLL where we operate, has evolved over the past few years. One significant factor we did not anticipate was the impact of COVID on the market, which led to a substantial decrease in new patients. This was not considered in our previous forecasts. Additionally, we are facing more competitive pressure in terms of pricing and volume than we expected. Despite this, Venclexta is performing well and has exceeded some of our initial expectations during its launch. All these factors influence what we are discussing. We've also made good progress in expanding our HemOnc portfolio from a research and development perspective. The assets I mentioned earlier have substantial potential. For instance, Venclexta targeting the t(11;14) multiple myeloma population presents a notable opportunity, and we anticipate receiving updates soon. We believe this will enhance both in-patient therapy and overall revenue for the franchise. Other promising opportunities include Navitoclax, epcoritamab, and ABBV-383, which can also drive growth. I maintain confidence in our capacity to grow our HemOnc franchise. However, I must acknowledge that Imbruvica is experiencing more competitive pressure than we had anticipated. When we issued our guidance, we did not fully account for follow-on BTKs being a significant factor. Nonetheless, I remain confident that our HemOnc franchise will grow and contribute positively to the company in the long term.
Jeff Stewart, CFO
Yes. Hi Vamil, it’s Jeff. So, just to answer your question on Ubrelvy in the overall market. Certainly, we’re very pleased, as I mentioned in my remarks, over the momentum on Ubrelvy. We continue to lead in that acute space. And the early results for Qulipta are also very strong. Now, a lot of it is going to depend on how that CGRP market develops. So, if you think about it in this way, and this is how we think about it is, is it’s about in terms of new patient capture for the total Ubrelvy market, where we also compete with another player from Biohaven. It’s about 18% to 19% of the market. And the market is also with the expanded triptan market, of course. So, if you look at that, the payers certainly like you to step through one or more triptans. When you look at the population that may not be eligible for a triptan or fails a triptan, the estimates are typically up to 30% to 35%. And so, the market has potential room to sort of double into that epidemiology. So, you can kind of run the numbers there. I mean, we often get the question, is it over $1 billion? Is it closer to $1 billion or is it closer to a higher number. But nonetheless, we’re pleased. Certainly, it’s exceeded our expectations so far, and Qulipta has as well. So, I think there’s more room for the market to run, but we’ll have to see. I mean, there are payer pressures in the market, as I mentioned, in terms of the step-through therapy.
Operator, Operator
Our next question comes from Steve Scala from Cowen.
Steve Scala, Analyst
I have a couple of questions. At a high level, I struggle to understand why 2022 won’t be a stronger year than the guide on the earnings line. Skyrizi and Botox are doing phenomenally. Rinvoq is holding its own. Humira will still be exclusive in the U.S. for the whole year and should be at peak profitability and the pandemic less an obstacle. So, why won’t 2022 look more like or even better than 2021 in terms of earnings power? And secondly, there was no mention of the CF program even in the upcoming milestones. Any thoughts on the timing of the triplet data? In the past, I would describe AbbVie confidence as being no more than moderate. Has it changed one way or the other?
Rick Gonzalez, CEO
Steve, this is Rick. Maybe Rob and I will tag team your first question, and then Michael will cover your second question. I think if I look at 2022 and I look at our overall performance coming off of a strong year in 2021, it’s pretty impressive performance. When I look at the EPS growth, certainly, do we have an opportunity to drive it harder? I can tell you, every year, we endeavor to drive it as hard as we can drive it. And when I look at all of the businesses individually, and I look at their ability to be able to perform, I’m extremely confident in the trajectory that we have going forward. Specifically, we’re assuming as an example, in HCV that there’s still a COVID impact in HCV. So, I wouldn’t say the pandemic is completely gone in 2022. But, I’d say, overall, the brands are performing well. We’re investing in the business to ensure that we continue to be able to drive long-term performance. And so certainly, that obviously drives some expectations around what the EPS growth will be year-over-year. I don’t know, Rob, anything you’d like to add?
Rob Michael, CFO
I mean, I think it’s a good point and that we are fully investing to support the long-term growth. If you think about we’re launching AD, that’s a new area for us. Qulipta and Vuity, we’re also going to fully invest there. Aesthetics, we’ve seen that the strength of the investment in aesthetics in the way we’ve been able to grow the market. So that’s really important. At the same time, we’re expanding operating margin. We’re exceeding our expectations for synergies. And so, you’re seeing us deliver another year of operating margin expansion. So, I’d say, we’re top tier in operating margin, very healthy P&L profile. And then, the other thing that you probably have to factor in here is that we’ve assumed half year Restasis as well. We don’t really have visibility to the generic until we make an assumption every time we update guidance six months out. So that’s something that if you look at year-over-year that you should figure into your comparisons. But overall, we’re very pleased with delivering double-digit growth in earnings and seeing another year of very strong operating margin expansion while fully investing to support the growth of the business.
Michael Severino, President
And this is Mike. I’ll take the question on CF. I think it’s important to keep in mind that this is a pre proof-of-concept program that doesn’t contribute in any meaningful way to our long-term outlook and doesn’t factor into our thinking about the long-term potential in the pipeline. And the way we have discussed it is consistent with that view. We’ve always said that it represents significant upside if it were to hit, but it’s an early program. With respect to the timing of the data, we continue to track towards the timing that we’ve described previously. We would expect to have data from the triple, sufficient to enable a go/no-go decision later on this quarter.
Operator, Operator
Our next question comes from Tim Anderson with Wolfe Research.
Tim Anderson, Analyst
A couple of questions. I’m guessing that as we move through 2022, investors are going to start to have some concerns about 2023 earnings, what the impact from Humira could be, and you talked about having more visibility on Humira contracting later this year. My question is, is it possible you’ll actually give us 2023 earnings guidance sometime this year, like at Q3 results as an example? And then, my second question, just going back to CF data. You said in mid-November that you would actually have that data in-house by the end of the year. So, here we are four weeks later, we haven’t really seen anything. My question is, do you actually have that data in-house? Did you hit that timeline of end of year, if not, what’s going on? And what changed in that short window?
Rick Gonzalez, CEO
Okay, Tim, this is Rick. I’ll address your first question, and Mike can handle the second. We are now able to commit to providing earnings guidance for the third quarter. We should be able to offer better insight into the erosion curve, which could help inform our earnings guidance. If we're in a position to confidently provide that guidance, we will. We anticipate having good visibility into the erosion curve, at which point we can refine our estimates and provide greater specificity. We recognize this is a significant issue for investors. Regarding EPS, we have indicated that we expect a decline in 2023, so this should not come as a surprise to any investor. It is crucial for us to communicate this accurately to the investment community and provide guidance around it. Once we are able to do so reliably, we are committed to doing it. We will see how things develop, and by the time of our third quarter call, we should be in a better position to offer more clarity. Mike?
Michael Severino, President
So, on CF, what we said towards the end of last year is that data would begin to come in-house around the end of the year, and we would have sufficient data to make a go/no-go in the first quarter. And we’re still tracking to that overall timeline. There were some challenges towards the end of the year, where a number of patients were expected from Australia, for example, and Australia shut down because of COVID and we had to shift that enrollment. So, we perhaps have slightly less data than we would have hoped to have had at this point in the year. But again, we’re still tracking to be able to make that go/no-go decision by the end of the year, because it’s important to keep in mind that these are short studies. And so once you get those patients in, you can turn the data around and make a decision pretty quickly. But the overall timing hasn’t changed substantially from what we described at the end of last year.
Operator, Operator
Our next question comes from Mohit Bansal from Wells Fargo.
Mohit Bansal, Analyst
Congrats on the quarter. Maybe a question on Rinvoq and other oral competition and competitors in IBD, where do you see Rinvoq fitting versus other orals such as SNP inhibitors? I mean, now they are more than one. And KOL, I mean they kind of suggested some kind of induction with one drug in maintenance with other drugs, a kind of treatment paradigm in IBD. Do you think it is even a possibility in any of these diseases? Thank you.
Michael Severino, President
This is Mike. I'll take that question. If you look at the performance of Rinvoq in inflammatory bowel diseases, both in ulcerative colitis where we have the complete data set and in Crohn’s disease, where we have significant induction data, the performance overall is very strong. This is evident not just in the overall response rates but especially when evaluating deeper response measures such as clinical remission, mucosal healing, and major clinical response, which combines remission with endoscopic improvement. We are achieving high levels of disease control, and we believe this aspect of the drug, along with its favorable benefit-risk profile, positions us well against not only oral competitors but all competitors in the field. When we analyze this data, despite the challenges of cross-study comparisons, we find response rates that are unmatched in the field. Thus, we believe there is a significant opportunity for Rinvoq, and our perspective on its role in inflammatory bowel disease reflects that. Regarding mixed induction and maintenance regimens, it's key to note that no data supports those approaches. All programs examine induction followed by maintenance, usually involving a reduced dose from the induction dose. That's the data set available to physicians. Additionally, it's important to recognize that, over time, patients often lose control and may require reinduction with a new agent. One of Rinvoq's notable strengths, which Skyrizi also shares, is its durable response. It maintains efficacy for an extended period in the studies we have tracked, including our long-term extensions from Phase 2 and the Phase 3 program. So, we consider these to be strong attributes of the products.
Operator, Operator
Our next question comes from Gary Nachman from BMO Capital Markets.
Gary Nachman, Analyst
Aesthetics has been a big source of upside in 2021. So, I’m curious, did you see any real impact from Omicron in the fourth quarter? Do you see a tailwind maybe from that further recovery this year? Is that baked into the aesthetics guidance of $5.9 billion that you have for 2022? And you’ve talked about high-single-digit long-term aesthetics guidance, but this year should be double digits. So, should we be thinking more along the lines of double-digit growth maybe for the next few years if you’re still investing a lot in that space? And then, just one other quick one on Qulipta for the chronic migraine prevention indication. That data is coming soon sometime this quarter. So, just talk about how meaningful you think that indication will be and how that’s factored into the peak targets that you talked about. Thank you.
Rick Gonzalez, CEO
Gary, it’s a good question on Omicron in new studies because it is something we track very carefully in every major geography around the world as well as by state here in the United States. And I will tell you that at least as far as the U.S. is concerned, there has not been much of an impact on aesthetic volume, unlike what we saw when there was an actual shutdown. And obviously, you would think shutdown, you’re going to see the volume go down. But I’d say here, we’re seeing very little impact on the volume. So, we have factored in that we don’t expect a major disruption going forward. And I think the data would clearly support that that’s a reasonable position to take. And as far as the business overall, I mean, I can tell you, we’re very pleased with how the business is performing. I think that group is executing at a very high level. And certainly, the resourcing and the dedicated structure that we put in place, I think, are helping a lot in major geographies like the U.S. and China. We’re obviously comfortable with the guide that we provided. It is an area that we’re going to continue to invest in and continue to drive. And I think it’s a market that I think is extremely attractive. And it’s going to require both us to continue to execute and invest in it appropriately to grow the market, but also to build out more assets that meet patients’ needs to be able to expand the market. And so, we’ve almost doubled the R&D investment that we have in aesthetics since we took it over. And we have a number of programs that I think are very exciting programs. Some of the biostimulatory and regenerative fillers that we’re working on now, I think, could be exciting opportunities like tropoelastin to be able to stimulate tropoelastin in patients using fillers is an exciting program that continues to advance. And so, it’s going to require both. It’s something that we’re absolutely committed to continue to drive. And I think this can be, as we indicated in our comments, I think this can be a strong business for AbbVie over the long term. Jeff, do you want to cover Qulipta?
Jeff Stewart, CFO
Yes. And what we see is that there is excitement about Vuity. I mean it’s different than the obviously the market is basically over-the-counter or prescription high glasses or readers, right? So, this is the first ever product that basically is a drop or a reading drop, right? So, when we start to break down the data and you take a really, really big market, tens and tens of millions of patients with presbyopia. But we also largely see from the clinical study, it really works the best for moderate to severe younger people, not older people. So, as we basically make the cuts, it’s still a substantial market size, but it’s not as large as you might think if you just look at all the presbyopes that are better in the United States. But nonetheless, it’s early days where we have a sales force that’s calling on our optometrist, also ophthalmologists. What we see from the early results is significant interest. We haven’t started our big consumer push, which will come later, later in this quarter. It is an older glaucoma product that’s been reformulated. So, there’s a little bit of learning from the ophthalmologists who really understand glaucoma products. But overall, the early results are it works, it works as anticipated. It works quickly within 15 minutes. It lasts for 6 to 8 hours. And so, again, when we look at the price point, it’s not a reimbursed product. It’s a cash pay product. We have, to Rick’s point, fairly modest expectations. And we’ll continue to watch the trajectory here over the next quarter or so.
Rick Gonzalez, CEO
I think the big assumption that you have to look at here is, what is the utilization per month the patient would actually use it for? I mean, as an example, I keep bugging the guys that I have to go get a prescription for it. Now, what do I want it for? When I go to a restaurant, I have trouble reading in low light. So, I’ll use it for that purpose. And so, it’s very difficult to come up with what the frequency at which it will be used. If it’s used in a high frequency, it will obviously be a bigger product. If it’s used at a relatively low frequency, it will be smaller product. So, we’ll have to see how it plays out.
Operator, Operator
Operator, we have time for one final question.
Operator, Operator
Thank you. Our final question comes from Matthew Harrison from Morgan Stanley.
Matthew Harrison, Analyst
Thanks for fitting me in. I guess, two for me, if I may. So first, on Epcoritamab, could you just comment around your confidence around accelerated approval here in DLBCL and how you’re thinking about that opportunity in the near term? And then, on Vraylar, maybe just comment on what FDA conversations are ongoing there and how you’re thinking about the potential for an AdCom or not.
Michael Severino, President
We have a high level of confidence in Epcoritamab overall. It continues to show strong results, with high overall response rates, deep responses, and good complete response rates for various indications, including DLBCL and follicular lymphoma. Regarding the confidence in obtaining accelerated approval for diffuse large B-cell lymphoma, the data indicates that it surpasses the benchmarks of existing therapies for highly pre-treated refractory patients. Therefore, we believe that the data should support accelerated approval and will allow it to mature from the expansion cohorts before our final regulatory discussions later this year to prepare for the submission. This is already part of our plans, and we find it well-supported by the data. Concerning Vraylar and major depressive disorder, we are confident in our position. Our confidence was established when we evaluated the strength of the data and relevant precedents for similar treatments in depression and as an adjunctive therapy for major depressive disorder. We have completed all necessary regulatory discussions for the submission and plan to submit shortly, as mentioned in my earlier remarks. While it is still early to comment on the likelihood of an advisory committee meeting, we usually begin discussing that with the agency a few months into the review process. Based on the data and prior cases, we do not expect one, but if the agency decides to hold one, we would not be concerned. We believe our data package is robust and would stand up well.
Operator, Operator
Thanks, Matthew. That concludes today’s conference call. If you’d like to listen to a replay of the call, please visit our website at investors.abbvie.com. Thanks again for joining us.
Operator, Operator
Thank you. That concludes today’s conference call. Thank you for your participation. You may disconnect at this time.