Earnings Call Transcript - ABBV Q2 2021

Operator, Operator

Good morning. Thank you for standing by, and welcome to the AbbVie's Second Quarter 2021 Earnings Conference Call. All participants will be able to listen only until the question-and-answer portion of this call. I would now like to introduce Ms. Liz Shea, Vice President of Investor Relations. Ma’am, you may proceed.

Liz Shea, Vice President of Investor Relations

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, Executive Vice President and Chief Financial Officer and Jeff Stewart, Executive Vice President, Commercial Operations. 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, I remind you that 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 has been recast to conform to AbbVie’s revenue recognition accounting policies, and exclude the divestitures 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, Chairman and CEO

Thank you, Liz. Good morning, everyone, and thank you for joining us today. I'll discuss our second quarter performance and outlook. And then Jeff, Mike and Rob will do our business highlights, pipeline progress and financial results in more detail. AbbVie delivered another excellent quarter with adjusted earnings per share of $3.11, exceeding the midpoint of our guidance by $0.04. Total adjusted net revenues of nearly $14 billion were up 19.3% on a comparable operational basis, approximately $375 million ahead of our expectations. These results demonstrate our strong and balanced performance across each of our major growth franchises, including double-digit comparable operational revenue growth from immunology, hematologic oncology, neuroscience and aesthetics. Looking at the most recent trends, the vast majority of our portfolio is well into the recovery phase from the pandemic. In immunology, we continue to see strong recovery across the dermatology and gastroenterology segments with positive trends across all key indicators, including new patient starts. SKYRIZI and RINVOQ continue to ramp nicely in their initial indications, with both products demonstrating robust double-digit sequential revenue growth. In neuroscience, Vraylar is demonstrating strong new prescription volume in the atypical antipsychotic market and the launch of Ubrelvy, the leading oral CGRP for acute migraine continues to exceed our expectations. Aesthetics continues to perform well above pre-COVID levels exceeding our internal expectations. We're pleased with the rapid market growth in both toxins and fillers, driven by our increased promotional resources globally, brand strength and COVID-related pent-up demand. Rapid global market demand is expected to remain well above historical levels in the near to medium-term and we are raising our full year guidance once again for aesthetics. While the recovery across the AbbVie portfolio is going very well in aggregate, in certain disease areas like CLL and HCV, we continue to see a residual impact from the pandemic. We expect these specialty areas to further recover as the year progresses. One of AbbVie’s greatest strengths is the dedication and engagement of our people. Across AbbVie, the majority of our employees have safely returned to the workplace. And our field teams are now predominantly conducting live engagements with physicians and customers, where protocols and guidelines permit. I'm extremely proud of the teamwork and collaboration our people have demonstrated throughout this pandemic to bring our medicines to patients and keep our business performing at a strong level. As an organization, we have also made a tremendous amount of progress with the Allergan transaction and integration. We just recently completed our first full year as a combined company, which I'd say has gone exceptionally well. We're tracking well against the operational and financial commitments we outlined at the time of the transaction, with a crucial performing above our original projections. But I'm particularly pleased with the robust revenue performance that we've been able to drive since acquiring Allergan. With 2021 sales tracking to grow significantly faster than legacy Allergan’s historical performance. Our results continue to show that we have created a stronger and much more diverse company with numerous products within our newly combined portfolio delivering robust growth. Based on the continued strong momentum of our business in the quarter and our progress year-to-date, we are once again raising our full year 2021 EPS guidance. We now expect adjusted earnings per share of $12.52 to $12.62, reflecting growth of 19% at the midpoint. Our strong performance allows us to continue to fully invest in the business for long-term growth. As you'll hear from Mike momentarily, we continue to make excellent progress across all stages of our research and development programs. In closing, I'm extremely pleased with our performance in the quarter and with our continued strong momentum of the business, which has positioned us well for the remainder of 2021 and many years to come. With that, I'll turn the call over to Jeff for additional comments on commercial highlights.

Jeff Stewart, Executive Vice President, Commercial Operations

Thank you, Rick. I'll start with immunology, which delivered global revenues of more than $6.1 billion, reflecting growth of 13.8% on an operational basis. SKYRIZI and RINVOQ continue to have significant impact on AbbVie’s growth and performance, contributing more than $1 billion in combined sales this quarter. SKYRIZI global revenues were up 17.4% on a sequential basis, reflecting increasing market share globally. In the U.S., SKYRIZI continues to perform well and has maintained its leading in-play psoriasis patient share, which includes both new and switching patients at approximately 34%. SKYRIZI’s total prescription share capture is now approaching 20%, second only to Humira. Internationally, SKYRIZI has achieved in-play patient share leadership in 13 markets, including Canada, France and Japan. RINVOQ is also demonstrating robust growth with global sales up nearly 25% on a sequential basis. We continue to see in-play patient share of approximately 15% in the U.S. RA market, where physician and patient feedback remain very positive on RINVOQ’s strong benefit-risk profile. Internationally, RINVOQ access and share continue to ramp nicely in RA, with in-play market leadership now in half a dozen key countries. We are also making excellent progress with the regulatory approval and commercial launch of PSA and AS across several OUS countries. And we look forward to the approval and commercialization of RINVOQ in atopic dermatitis later this year following the recent CHMP positive opinion for both the 15-milligram and 30-milligram doses. Humira global sales were approximately $5.1 billion, up 3.6% on an operational basis, with continued high single-digit revenue growth in the U.S., offset by biosimilar competition across the international markets, where revenues were down 12.6% on an operational basis. In hematologic oncology, sales were approximately $1.8 billion, up 13.2% on an operational basis. AbbVie maintains a strong leadership position in CLL with a combined portfolio that includes both Imbruvica and Venclexta, new patient share of approximately 42% and total patient share of approximately 72% across all lines of therapy. Imbruvica global revenues were approximately $1.4 billion, up 7.2%. In the U.S., performance continues to be impacted by lower new patient starts in CLL, which remain below pre-COVID levels, as well as increasing competitive dynamics from newer therapies, including Venclexta and other BTK inhibitors. Venclexta sales increased 38.3% on an operational basis with strong demand across all approved indications. We're particularly pleased with the performance in AML with robust share in the U.S. and increasing momentum internationally following recent approvals in the EU and Asia. In neuroscience, revenues were more than $1.4 billion, up 29.6% on a comparable operational basis. We continue to see strong momentum with Vraylar, which recently achieved multiple all-time highs in weekly prescriptions and market share. Vraylar revenues of $432 million were up more than 25% on a comparable operational basis. And Ubrelvy once again delivered robust results. Sales of our leading acute migraine treatment were $126 million, exceeding our expectations. Feedback from physicians remains very positive, highlighting Ubrelvy’s rapid and sustained pain relief, safety, convenient and flexible dosing profile and overall commercial access. Ubrelvy is now capturing roughly 9% of new prescriptions in the large acute migraine market, with more than 1 million cumulative total prescriptions since the launch. We continue to believe there is substantial room for long-term growth in this rapidly expanding acute market based on unmet need and strong patient demand. In migraine prevention, we've also been planning and preparing for the forthcoming regulatory approval and commercial launch of Atogepant, our oral CGRP for episodic migraine. We're very encouraged with the efficacy profile of Atogepant, including reduction in migraine days versus placebo, as well as the overall percentage of response rates in patients. Now the launch of Atogepant will be supported by our existing migraine sales force with commercial access expected to ramp strongly, we remain on track for a U.S. regulatory decision in September. Botox Therapeutics continues to perform well across nearly a dozen medical indications, with total sales of $603 million, up more than 38% on an operational basis. In chronic migraine, Botox Therapeutic remains a foundational prevention treatment, and the clear branded leader in new patient starts. Lastly, in our other therapeutic areas, we saw significant contribution from eyecare, which had revenues of $919 million, up 24.1% on a comparable operational basis. Mavyret sales were $442 million, up 13.9% on an operational basis, although treated patient volumes remain suppressed versus pre-COVID levels. And we also saw double-digit comparable operational revenue growth for both Creon and Linzess. So, overall I'm pleased with the momentum of our therapeutic portfolio, which is demonstrating a strong recovery, as well as our progress with new recent product launches. And with that, I'll turn the call over to Mike for additional comments on our R&D programs.

Michael Severino, Vice Chairman and President

Thank you, Jeff. I'll start with immunology where we had several notable pipeline events in the quarter. In the area of inflammatory bowel disease, we reported positive top line results from the Phase 3 maintenance studies for RINVOQ in ulcerative colitis, and SKYRIZI in Crohn's disease. In the RINVOQ UC maintenance study, both the 15 and 30 milligram doses met the primary and all secondary endpoints at week 52. In the induction portion of the program, RINVOQ demonstrated a very strong impact on the disease. And the results from this maintenance study demonstrate that patients continuing treatment with RINVOQ maintain high levels of clinical remission, clinical response, and endoscopic improvement at the one-year mark. In fact, maintenance treatment with either dose of RINVOQ resulted in some of the highest rates of remission and endoscopic improvements seen in UC clinical studies. With the 30 milligram RINVOQ dose, 52% of patients achieved clinical remission, 62% achieved endoscopic improvement, 49% achieved histologic endoscopic mucosal improvement, and 68% achieved steroid-free remission. We are very pleased with how RINVOQ performed from a safety perspective as well. In this maintenance study, the exposure adjusted event rates for overall adverse events, including serious and severe events were higher in the placebo group than in either RINVOQ dose group. Additionally, the exposure adjusted rates for MACE, VTE and malignancies, excluding non-melanoma skin cancer were comparable between RINVOQ groups and placebo. These results provide further evidence that RINVOQ has the potential to become a highly effective therapy for patients with moderate to severe ulcerative colitis. We're also nearing completion of the Crohn's disease program for RINVOQ and expect to see data from the first Phase 3 induction study later this year. Results from the second induction study and the maintenance study are expected in the first half of next year, with regulatory submissions also anticipated in 2022. We also saw very impressive results from SKYRIZI in the maintenance phase of our Crohn's disease program, particularly with the 360 milligram maintenance dose, which met the co-primary endpoints of clinical remission and endoscopic response versus the withdrawal arm at week 52. Importantly, when we look at the most stringent endpoints, we see strong separation between SKYRIZI 360 milligrams and control with the response rates of 39% for endoscopic remission, and 29% for deep remission, compared to 13% and 10% for the withdrawal group at week 52. We remain on track to submit our regulatory applications for RINVOQ in UC and SKYRIZI in Crohn’s in the coming months. In the quarter, we also announced updates regarding our regulatory applications for RINVOQ in atopic dermatitis, psoriatic arthritis, and ankylosing spondylitis. In June, RINVOQ received a positive CHMP opinion in Europe recommending both the 15 milligram and 30 milligram doses in moderate to severe atopic dermatitis. This CHMP opinion puts us on track for European approval in August. When approved, atopic dermatitis will be the fourth indication for RINVOQ in Europe. Regarding our supplemental NDAs in the U.S., we recently announced that we were notified by the FDA that they would not need our PDUFA action dates for RINVOQ in psoriatic arthritis, ankylosing spondylitis, and atopic dermatitis, which were in late June for psoriatic arthritis and AS and mid-July for atopic dermatitis. The agency cited their ongoing review of the tofacitinib oral surveillance study indicating that they needed more time to complete their reviews of the data. The FDA has not requested any additional safety analyses for RINVOQ since the PDUFA dates were missed. While there are no new action dates, based on our discussions with the agency, we expect decisions on our regulatory applications in the next few months following completion of the agency's review of the tofacitinib oral surveillance data. We remain confident in the benefit-risk profile for RINVOQ across all indications and we'll continue to work with the FDA to bring RINVOQ to market in these new disease areas. In our early-stage immunology pipeline, we recently began two new trials for ABBV-154, our TNF-steroid conjugate. We initiated a definitive dose-ranging study in patients with RA and also started our Phase 2 study in polymyalgia rheumatica. Later this year, we expect to begin the Phase 2 study for ABBV-154 in Crohn's disease. Also in the quarter, we completed the induction stage of a Phase 2 proof-of-concept study evaluating ravagalimab in ulcerative colitis patients. While this CD40 antagonist demonstrated greater efficacy compared to historical control, the efficacy results did not meet our pre-specified criteria. As a result, we will not be advancing ravagalimab in ulcerative colitis. In oncology, we continue to make good progress across all stages of our pipeline. At the recent ASCO and EHA meetings, data were presented from the GLOW and CAPTIVATE studies evaluating a Fixed Duration Imbruvica and Venclexta regimen in CLL patients. Results from these two studies demonstrated that the all-oral Fixed Duration Imbruvica plus Venclexta regimen has the potential to provide deeper and more durable remission and extends progression-free survival as a frontline treatment across the spectrum for the age and fitness status for CLL patients. We plan to submit these data to regulatory agencies and look forward to bringing this new Fixed Duration treatment option to CLL patients once approved. Earlier this month, we received a breakthrough therapy designation for Venclexta in combination with azacitidine for previously untreated higher-risk MDS patients, based on the strong data demonstrated thus far in our ongoing Phase 1b study. We expect to see final results from this study in the coming months and plan to discuss the data with regulators regarding the potential to support an accelerated approval for Venclexta in MDS. Also in the quarter, we saw interim results from a Phase 1 study evaluating the BCMA CD3 bispecific antibody TNB-383B in multiple myeloma patients who have received at least three prior lines of therapy. TNB-383B performed very well as a monotherapy in these heavily pretreated patients, demonstrating an objective response rate of nearly 80% and a very good partial response or better rate of 63% and a complete response rate of nearly 30% at doses greater than 40 milligrams in the dose escalation cohort. Based on these promising results, we exercised our right to acquire TNB-383B from Teneobio. We expect the transaction to close in the coming months, and we’ll provide more information on our development plan for TNB-383B in multiple myeloma later this year. This is a highly competitive area. But based on the data to-date, we believe this BCMA CD3 bispecific has the potential to be differentiated on efficacy, safety and dosing interval and could be best in class as both a monotherapy and combination therapy across lines of treatment in multiple myeloma. We continue to make good progress with the navitoclax program in myelofibrosis, which consists of randomized Phase 3 trials in both the frontline and relapsed refractory setting, as well as a single-arm Phase 2 study. Based on feedback from the FDA, we intend to submit our regulatory application with randomized Phase 3 data together with the Phase 2 trial results. We expect the Phase 3 data readout and regulatory submissions in the second half of 2022 with navitoclax approval in myelofibrosis anticipated in 2023. In neuroscience, we recently completed the Phase 2 proof-of-concept studies for two assets, elezanumab in multiple sclerosis and ABBV-8E12 in Alzheimer’s disease. In the respective studies, neither assay met the efficacy endpoints of the trial. And we will be discontinuing the development of elezanumab in MS and ABBV-8E12 in Alzheimer's disease. Given the enormous unmet need in Alzheimer's disease, we remain committed to finding disease-modifying therapies. And we continue to pursue a range of approaches. We have several additional programs that are either in the clinic today or in preclinical development. These include programs that modulate the neuroinflammatory response in Alzheimer's disease, such as our TREM2 and CD33 programs that are both in clinical development and programs that target pathologic tau through novel mechanisms, such as approaches that target intracellular aggregates for clearance that are in preclinical development. Following the accelerated approval of aducanumab in the U.S., there has been an increased focus on a-Beta-directed programs. We have monitored this area closely over the last several years. And based on all the available data, we believe there is a continued opportunity for an a-Beta-directed monoclonal antibody that clears plaque more rapidly than existing agents with a reduced risk of amyloid-related imaging abnormalities. We have profiled a number of a-Beta antibodies preclinically. And we have a candidate with the potential to meet these requirements. We expect to introduce this candidate into the clinic by the end of this year or early next year. Also in neuroscience, we're nearing completion of our registrational program for ABBV-951 in advanced Parkinson's disease. We recently completed an interim analysis in the first of two Phase 3 studies where our subcutaneous Levodopa Carbidopa delivery system demonstrated safety and efficacy comparable to DUOPA after six months of treatment. The primary objective of this trial was safety, but efficacy was also evaluated as secondary endpoints. In this analysis, ABBV-951 performed very well, demonstrating a 52% reduction in normalized off time, and a 41% increase in normalized on time without troublesome dyskinesia. Patients also benefited from ABBV-951's 24-hour continuous Levodopa Carbidopa infusion, with patients experiencing substantial benefits in sleep and reduction in morning off time. Full data from this six-month interim analysis will be presented at a medical meeting later this year. Data from a second Phase 3 study are expected in the fourth quarter with our regulatory submissions anticipated later this year or early next year. And lastly, in eyecare at the recent meeting for the American Society for Cataract and Refractive Surgery, we presented results from the Phase 3 Gemini 1 study evaluating our topical eye drop AGN-190584 for the treatment of symptoms associated with presbyopia. In this study, AGN-190584 demonstrated improved near vision without impacting distance vision, with a rapid onset of action within 15 minutes, and sustained vision improvements for up to six hours. AGN-190584 has the potential to be a convenient, on-demand solution for patients with mild to moderate presbyopia, and we look forward to an approval decision later this year. So, in summary, we've made great progress with our pipeline in the first half of this year. And we look forward to several additional data readouts, regulatory submissions and approvals throughout the remainder of 2021. With that, I'll turn the call over to Rob for additional comments on our second quarter performance and financial outlook.

Rob Michael, Executive Vice President and CFO

Thank you, Mike. Starting with second quarter results, we reported adjusted earnings per share of $3.11, up 32.9% compared to prior year and above our guidance midpoint. Total adjusted net revenues were nearly $14 billion, up 19.3% on a comparable operational basis, excluding a 1.6% favorable impact from foreign exchange. The adjusted operating margin ratio was 49.7% of sales, an improvement of 260 basis points versus the prior year. This includes adjusted gross margin of 82.2% of sales, adjusted R&D investment of 11.3% of sales, and adjusted SG&A expense of 21.2% of sales. Net interest expense was $606 million, and the adjusted tax rate was 12.6%. As Rick previously mentioned, we are raising our full year adjusted earnings per share guidance to between $12.52 and $12.62, reflecting growth of 19% at the midpoint. Excluded from this guidance is $6.48 of known intangible amortization and specified items. This guidance now contemplates full year revenue growth of 10.7% on a comparable operational basis. At current rates, we now expect foreign exchange to have a 0.9% favorable impact on full year comparable sales growth. This implies a full year revenue forecast of approximately $56.3 billion. Included in this guidance are the following updated full year assumptions. We now expect aesthetics global revenue of approximately $4.9 billion, including approximately $2 billion from Botox Cosmetic, and approximately $1.4 billion from Juvederm. We now expect Restasis sales of approximately $1.1 billion and assume no generic competition in 2021. For Ubrelvy, we now expect sales of approximately $500 million. For women's health, we now expect global revenue of approximately $900 million. And for Mavyret, we now expect global sales of approximately $1.9 billion. Looking at the P&L for 2021, we are now forecasting adjusted R&D investment of approximately $6.7 billion and adjusted SG&A expense of approximately $11.9 billion. All other full year assumptions remain unchanged. As we look ahead to the third quarter, we anticipate net revenue of approximately $14.3 billion. At current rates, we expect foreign exchange to have a 0.5% favorable impact on comparable sales growth. We expect adjusted earnings per share between $3.18 and $3.22, excluding approximately $1.64 of known intangible amortization and specified items. Finally, we continue to make great progress on our Allergan transaction commitments. We are exceeding our revenue expectations in several areas, including Botox, Vraylar, Ubrelvy, and eyecare. We've also delivered expense synergies of almost $800 million during the first half of this year and are on track to deliver synergies of approximately $1.7 billion in 2021 and greater than $2 billion in 2022. And we have already paid down $12 billion of combined company debt. We expect to achieve $17 billion of cumulative debt paid down by the end of this year, with further deleveraging through 2023. This will bring our net leverage ratio to 2.4 times by the end of 2021 and approximately two times by the end of 2022. In closing, AbbVie has once again delivered outstanding performance. And we are very pleased with the strong momentum of the business heading into the second half of the year. With that, I'll turn the call back over to Liz.

Liz Shea, Vice President of Investor Relations

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, first question please.

Operator, Operator

Thank you, Ms. Shea. Our first question is from Vamil Divan with Mizuho Securities. Your line is open, sir.

Vamil Divan, Analyst

Great. Thanks very much for taking my questions. So maybe two if I could. So one, Rick, you mentioned some of the Allergan products maybe doing better than your expectations. Can you maybe, I mean, I know you don’t want to share your secret sauce. But in terms of what is it that you've noticed that has helped to drive those products? Because it seems like it's pretty much across the board, from an aesthetic to Vraylar, Ubrelvy. So, is it around promotion efforts? Is it around some payor dynamics? Or anything you could share would be helpful there? And then the second one on Imbruvica. I just want to confirm, I think you guys said that the new patient share across all indications now is 42%. So, I just want to see you guys are in line with what you expect at this point. Obviously, there's been questions around some competitors that have entered the market. And maybe you can just talk about the patients who are not staying on Imbruvica. So, what are you seeing as the reasons why they might be choosing a competitor? Thank you.

Rick Gonzalez, Chairman and CEO

Yeah, Vamil, this is Rick. I'll cover certain part of the first question, and maybe I'll ask Jeff to jump in and cover any additional thoughts that he might have. I think as you look at this business, one of the things that I think AbbVie is sort of known for is that we tend to operate in a very focused and disciplined way, especially across what we consider to be growth franchises. We expect every one of our major businesses to develop plans to be able to maximize the value of their assets, both from a strategic long-term basis, but also from a short-term tactical basis. And I'll use aesthetics as the example. Early on, we made the decision that we were going to fully integrate the aesthetics business to make sure that it had the focus and attention that it needed because we believe this business had a significant opportunity to be able to grow. We did that globally. So, if you look at Allergan in the past internationally, those people representing those products also had to represent eyecare and other therapeutic products. So, we moved those out into the therapeutic areas of AbbVie internationally and solely dedicated the aesthetics group internationally to just their products. And then in the U.S., we operate with a similar structure and a fully integrated R&D organization that is totally committed to just developing aesthetics products and reports directly to Mike, and then the Head of the Business for aesthetics reports directly to me. And we had them develop a plan that they are now executing against to be able to deliver against that. So, I think it's really three aspects of it from my perspective. It's one, the structure we put in place. And that was a thoughtful, planned out structure. Two, it's the disciplined processes that we use to be able to execute across all of our businesses. And then third, I'd say we have consistently invested and we do invest in businesses that we think have the opportunity to be able to drive long-term growth and performance in a way that we can drive that at maximum speed. And certainly, as you look at aesthetics, we've increased the investment in SG&A and we've increased the investment in R&D. Jeff, anything you'd add?

Jeff Stewart, Executive Vice President, Commercial Operations

I think, Rick, the – I would agree, I think, a big piece Vamil, was the level of investment. So, as we looked at particularly the neuroscience compounds, Vraylar and Ubrelvy, we were able to structure the sales forces a little differently, which was important from commercial execution and also really upgrade and drive some of the investment around patient activation. So, I think that all of these brands are spectacular brands leadership position. And when we got that investment profile right, we've seen the response, so nothing that beyond that. Going back to your question on the hematology share, the 42% that I referred to was the combined AbbVie shares. So that's Imbruvica plus Venclexta across all lines of CLL. So, if you take a look, if I give you a little bit more color on the latest data that we have, for example, in frontline, we have 35% total AbbVie share, which is made up around 24% for Imbruvica and 11% for Venclexta. For second line share, for example, we have a 48% total AbbVie position, which is approximately 33% for Imbruvica and 15% for Venclexta. So, both of these brands are now operating at a very significant share level across CLL. I'll give you some more thoughts as you ask for in terms of color in the market. Beyond that leadership level that we have across the CLL indication, we do see that the CLL market is still suppressed. So, for example, patient starts year-to-date are down in the high single digits. And even within the quarter, they were down in the low single digits. We see that improving. And so that outlook looks to improve over the second part of the year. In terms of overall share dynamics, over the last several quarters, we have lost a few share points to Calquence, within the range of our expectations as they've ramped with their CLL ramp. But also interesting, we've seen that there's been some share increases in monotherapy CD20, which we think is also a COVID-type of effect that will ultimately revert back to normality as we go along through the pandemic. So overall, the franchise is performing very, very well. And as you heard from Mike, we're tremendously excited about the future of the hem/onc franchises as we move forward.

Rob Michael, Executive Vice President and CFO

And Vamil, this is Rob. I'm going to come back to your first question. Just one more thing we should mention is, we've been able to really leverage our international infrastructure. And so, we set up this business. We have the aesthetics franchise, fully focused internationally on that business whereas Allergan had combined with therapeutics. So, we've been able to bring that focus and the level of investment. I think we've also been able to leverage our market access prowess. So, we’re very strong across the globe. And so, when you think about the opportunities for us going forward, I think international certainly plays a big role as we leverage the Allergan business.

Liz Shea, Vice President of Investor Relations

Thanks, Vamil. Operator, next question please.

Operator, Operator

Thank you for your question. Our next question is from Chris Schott with JPMorgan. You may ask your question.

Chris Schott, Analyst

Great. Thanks so much. Just another one on aesthetics. Obviously, some incredibly strong numbers here. Can you just elaborate a little bit more on the sustainability of this growth? So, I guess I’m just trying to get a better sense of how much of what we're seeing right now is catch up as we exit lockdowns versus a more sustained step up in sales going forward? Just any color on that would be appreciated. My second question was RINVOQ in UC. Can you just put some of this data into context as you think about the competitive landscape, and particularly relative to what you had anticipated in your long-term guidance for this indication? I think you’re about $1 billion in IBD sales by 2025. And is that we've seen more of this data set, just how comfortable are you feeling with that target and ultimately the role RINVOQ’s going to play in this space? Thanks so much.

Rick Gonzalez, Chairman and CEO

Hey, Chris, this is Rick. I'll take the aesthetics question and then Mike can maybe cover the second question that you had. So, it's a great question. And it's one that we have been looking at very carefully. I mean, if you just step back and you look at the performance of the business, we've done a number of things to drive the business. We believe this business is significantly underpenetrated when you look at the available patient population here and your ability to drive long-term penetration is tremendous. And so, that's why we've done the things that we've done to try to drive that demand. Globally, the aesthetic sales were up 31%. If we look at the U.S. toxin and filler business, the markets up about 40% versus 2019. So, but it's hard to evaluate, I can tell you the vast majority of it is driven by fundamental demand. And we can see that through the funnel that we see patients coming in and how many of them are activated to go get procedures. But we just conducted a fairly robust market research study to try to understand how much of it was COVID-related. And we looked at things like how many of those patients got stimulus checks, how many of them were affected from an employment standpoint, and are now back at work? I'd say that study, if you looked at the data in that study, the conclusion that you would withdraw from that is very little of it is COVID-related. Now, I think the flaw is this, most patients are not going to say they used stimulus money for these kinds of procedures or other kinds of things. So, I think to the best of our ability, what I would tell you is about two-thirds of the performance, I think, is fundamental demand, and maybe one-third of it is pent-up demand. We're going to need a couple more quarters, I think to see how that plays out. But I'd say that's our best assessment right now. So, very robust growth either way, and it could sustain a little bit better than that. But I think, you can pretty well count on two-thirds of it being fundamental demand at sustainable longer term. Mike?

Michael Severino, Vice Chairman and President

I'll take the question on RINVOQ UC. What I would say is the data that we've seen from RINVOQ UC has exceeded our expectations from an efficacy perspective, and the results are very strong. UC has been very difficult to treat pharmacologically and getting high rates of remission. And this response has been challenging and both has delivered those now account just across number of studies. And I think from a safety perspective, it's also performed very well. I commented in my remarks, the fact that overall rates of these serious AEs are actually lower with RINVOQ than with placebo. Now the reason for that is that many of these AEs are driven by severity of disease, and with the improvement in the ease to use UC then improve as well. And with respect to events of interest, the safety profile has worked very, very well with their segment A, segment B and other events rates have been comparable to controls. And so overall, we feel very confident in the long-term guidance that we put out. But one thing that's important to keep in mind is that long-term guidance is 2025 guidance. And our IBD assets will be in relatively early stage of launch by that time. But the profiles that I've talked about not only for RINVOQ, but also for SKYRIZI bode well, not only for 2025 guidance, but for the long-term growth of that aesthetic as opportunity there as well.

Liz Shea, Vice President of Investor Relations

Thanks Chris. Operator, next question please.

Operator, Operator

Thank you. Our next question will be from Ronny Gal with Bernstein. You may ask your question sir.

Ronny Gal, Analyst

Good morning and thank you for the questions. My first question is about ABBV-951. You've mentioned the efficacy rates, but could you elaborate on the skin safety profile in comparison to the neogen product or apomorphine IV from Europe, particularly regarding more severe effects like abscesses and occlusions? My second question is about the pipeline concerning a-Beta. It didn't take long for you to engage with that. Can you discuss the science you're uncovering? Is the right strategy to achieve the best effect with minimal side effects to target plaque removal as effectively as possible, or should the focus be on soluble components and indirectly addressing plaque removal?

Michael Severino, Vice Chairman and President

Okay, so this is Mike. I'll address both questions. Regarding 951, we plan to present full data from the Phase 3 study at a medical meeting and ultimately publish it in peer-reviewed journals. From what we've observed, the skin safety profile appears to be favorable and meets our expectations. As expected with a cutaneous device, there are some mild local reactions, but these have generally been manageable and resolve with ongoing treatment. We haven't encountered significant problems with more severe skin issues, and we believe the patient-friendly nature of subcutaneous delivery, similar to an insulin pump, will provide a significant advantage. This method allows patients to achieve effective results without the complications associated with placing a gastric tube, which can be challenging to manage. We feel optimistic about the potential for 951. As for a-Beta, the data indicates that rapidly removing plaque should lead to benefits. The critical factor we need to achieve is significant reductions in plaque levels quickly, as we don't expect to see cognitive improvements until patients reach the amyloid negativity threshold of 20 centroids. Therefore, our aim is to get patients to that level as quickly as possible while minimizing the risk of related issues. We believe this can be achieved through careful epitope selection, considering the differences between amyloid forms present in vessel walls and plaque. We have preclinical data that supports our approach to do this with reduced risk. We now need to see if the clinical data aligns with our findings. We've had these candidates in mind even before the approval of aducanumab, as we have been monitoring this area closely. We believe this is the right time to move forward with these candidates and test whether the scientific principles we've outlined will hold true in clinical settings. Our strategy regarding a-Beta is focused on plaque, not soluble forms.

Liz Shea, Vice President of Investor Relations

Thanks, Ronnie. Operator, next question, please.

Operator, Operator

Thank you. Our next question is from Andrew Baum with Citi. You may ask your question.

Andrew Baum, Analyst

Many thanks. A few question, Jeff. Firstly, on the outlook for rebaiting and oncology, this is somewhat of a novelty, at least historically. I know that yes, excluded Calquence from their formulary, there's obviously increased therapeutic competition in the space. How should we be thinking about the rebaiting outlook and oncology going forward more broadly? Second, on the U.S. paybacks through COVID and now in the recovery stage, could you outline the magnitude of which you've had to increase and then decrease the Medicaid components in the patient assistance programs? Or whether you're seeing that improvements, some sense of scale and direction there? Many thanks.

Michael Severino, Vice Chairman and President

Yeah, thank you, Andrew. And to start with oncology. I mean, largely, as you know the rebaiting has been done through the sort of the GPO channel. And particularly with the physician in office dynamics that are in that sector, we don't see significant rebaiting happening at the PDM level. And if it is, it's quite modest. I think, certainly from the ESI standpoint that you highlighted, that was an ESI decision. That was not certainly something that AbbVie approached that particular payer with any sort of deal. Our philosophy is that these drugs are very important for oncologists to have basically open access for all of these agents. So, I think it is something that we've seen some of these lights that have started to turn on. But they've been quite modest. And I don't think that they're going to be a super accelerant that we should be overly worried about. That's my position on that. I think this the second approach in terms of sorry, that was the question on the magnitude of the Medicaid. Yeah, this has been quite interesting. We've seen, certainly on all of the data, the fact that the enrollment in Medicaid has gone up. When we look across our businesses at let's say, acute channel shifts in terms of the utilization, they're relatively modest. They're there, so we don't see massive movements around our channels shifting that link to the magnitude of what you might see in terms of the enrollments. So it's relatively modest, certainly manageable. And I think, certainly, as we see the jobs positioned come back and that could be quite strong, I think we'll see any modest movement will be corrected over the next several quarters.

Rick Gonzalez, Chairman and CEO

And this is Rick. Going ahead I'd add to the second question is so we have a very extensive and I would say generous PAP program in place that's really designed to ensure that patients who can't afford our medicines have the ability to be able to access those medicines free of charge in many cases. As an example, 99% of the applications we get for uninsured patients we approve we actually just increased the program to 600% of the federal poverty level across all of our brands. And so, it's a program that I think is designed to fulfill the mission that I just described. And that is that patients who need our medicines can get them from us if they can't afford to pay for them, or whatever system that they operate in. And but we have not seen and much to our surprise, we have not seen that program increased dramatically, even through COVID. And we advertise directly to patients that if they lost their job during COVID, that we would provide our medicines to them. But I wouldn't say, as I said, much to our surprise we didn't see the volume go up dramatically.

Liz Shea, Vice President of Investor Relations

Thank you, Andrew. Next question, please.

Operator, Operator

Thank you. Our next question is from Geoffrey Porges with Leerink. Your line is open, sir.

Geoffrey Porges, Analyst

Thank you very much. Lots of questions. But I'll focus first on RINVOQ. Rick, you've given the long-term guidance of recall $7 billion in revenue by 2025. I think, and by means correct me if I don't recall correctly. But if you only get the 15 milligram dose approved, if that's the outcome of the deliberations of the FDA, but you get the approvals in Europe, can you achieve that revenue guidance? You’re confident enough in the 15 milligram programme? And then secondly for Mike. You'll see us development program seems to have been sort of reactivated. And could you talk a little bit about your conviction, a little bit more detail on a 119? We don't know much about that. Are you confident that it can be active see through correct that matches up to your competition? Because clearly that's a big revenue opportunity that we have reflected in. Thanks.

Rick Gonzalez, Chairman and CEO

So, Jeffrey, this is Rick, on your first question. Yes, the guidance for RINVOQ is $8 billion. And I would say we're confident that even with a 15 milligram, we will sustain that guidance. If you look at the performance of the 15 milligram is quite remarkable. And so, we feel good about the performance of RINVOQ, we continue to see strong uptake of RINVOQ, and physician interest that is consistent with what we would expect. So, I think we're fine now.

Michael Severino, Vice Chairman and President

This is Mike, a context question on the CF program. When we restructured the collaboration with Galapagos. A few years ago, to take direct operational control of that program, we had a couple of goals. One is we wanted to make sure that we're optimizing the potentiator in C1 components of the regimen. We felt we had a best-in-class C1 in Q2. But we believed we needed to make a switch in the potentiator to one that we already had in hand. And we've done that. We also believe that we needed a C2 corrector. That’s in that time period a few years ago did not exist. So, we needed a C2 corrector that had the potential to be best in class. And so, what we did is we put a significant internal chemistry effort to come up with a number of compounds. 119 is the most advanced and a very promising one that we believe fit that bill. And based on all the preclinical profiling, we think 119 can be a best-in-class C2 corrector. And with the other components of our triple, we think we can deliver best-in-class efficacy with appropriate pharmacological properties, dosing, low DDIs, et cetera. And so, we are now in a proof-of-concept Phase 2 study in the clinic to determine whether those preclinical data will in fact spare out. What I would say here is the preclinical assays are good. They're much more predictive than they are in other areas because we fundamentally know what the defect is in CF, and we can study it in appropriate tissues in human tissues in vitro. But ultimately, we're going to need to see the clinical data. By right around the end of the year, we'll see internally proof of concept results for that triple. We'd probably be in a position to announce them externally early next year, and those will be data that will include impact on FET1 with a triple. And so that will tell us whether we can be best in class. And I agree if we are best in class, I think it's a very significant opportunity and we will progress it rapidly. Now, it's a proof-of-concept study. So, if it's successful, we'd have some additional dose ranging to do. We're studying the highest dose of 119, to determine whether it can have that effect we'd have to do some additional dose ranging to determine the optimal dose of 119, but that can be done rapidly. And then we would, if successful, move into Phase 3 development.

Liz Shea, Vice President of Investor Relations

All right. Thanks Mike. Thanks, Mike. Operator, next question, please.

Operator, Operator

Thank you. Our next question is from Steve Scala with Cowen. Your line is open, sir.

Steve Scala, Analyst

Thank you, a couple questions. Many of the questions so far suggest concerns around RINVOQ. But I'm wondering if this could all turn into be a positive. So, to what extent do you believe RINVOQ prescribing might be being held back by competitor product concerns? So, once those concerns are resolved and or RINVOQ emerges unscathed, if it does, RINVOQ could even do better. And we could be looking at a sharp acceleration in share gains and prescription trends in Q4. So, that's the first question. And secondly, on Humira contract renewals that will be signed in coming months for 2022. What is the typical duration of those contracts? Are they typically 12 months? 24 months, 36 months? If you can give us an idea of that that would be helpful. Thank you.

Michael Severino, Vice Chairman and President

Yeah, it's a very good question. And this question we fought a lot about, let me give you some perspective on RINVOQ. So, if you look at our, let's say, our demand performance, and I think I mentioned in my prepared remarks, we've been very consistent about 15% in place share in the large RA market, which is just under Humira, which has grown a little bit over the COVID times and since January to about 18%. So, we're very, very stable. And I do believe that there is some overhang on certain segments of prescribers that have, let's say, going back a little bit to TNF, really our own product, Humira. So, it's not outside of the realm of possibility as this resolves and really largely, as you probably heard, or seen Xeljanz has lost in play share over that period. So, I do believe there's a little overhang in certain, probably significant segments of Rheumatology. So, we are anxiously awaiting the resolution here of oral surveillance, which obviously has delayed our regulatory submissions. But it's not outside of the realm of possibility, given the very significant and differentiated data that we have in our packages, that we can see an acceleration as things resolve. But we're going to anxiously be monitoring. And certainly, be prepared to anticipate any outcome there.

Rick Gonzalez, Chairman and CEO

And see, this is Rick. On the contracting question, I'll handle that one. It varies quite a bit based on product and by managed care organization, but I'd say typically, so it can be some of them can be as short as 12 months, it's probably more common to be in a 24-month range from a contracting standpoint.

Liz Shea, Vice President of Investor Relations

Thank you. Great, thank you Tim. Operator next question, please.

Operator, Operator

Thank you. Our next question is from Matthew Harrison with Morgan Stanley. You may ask your question.

Matthew Harrison, Analyst

Great. Good morning. Thanks for taking the question. Just a follow-up question on CFP, I guess first two parts here. First, are you confident that you have a potentiator that's active and improve versus the Galapagos compound? Because I think we've seen a lot of issues with people trying to develop potentiators. They're as good as Kaleidoco. And then, second, I know you talked about FPV 1, have you looked at sweat chloride at all? Obviously, you need a larger patient sample size to get a good directional view on FPV 1. I'm wondering if we looked at smaller patient numbers on sweat chloride. Thanks.

Michael Severino, Vice Chairman and President

So, this is Mike. I’ll take that. With respect to the potentiator, we are convinced that we have a potentiator that has activity and we've changed the potentiator from some of those prior combinations that were pursued earlier on in the Galapagos collaboration. We think that, that potentiator it has clear signs of activity, we think the C1 character is very good and probably best in class based on the data that we have seen that were generated earlier in the collaboration. We put this up, the principal piece that was missing was that CTO and we think we have a good one. With respect to the endpoints while it does take a larger sample size to look at FPV 1 we feel like FPV 1 is what really matters here. That's what's going to translate into clinical benefit for patients. And so, our proof-of-concept study will show us FPV 1 and that's the primary measure that we are going to use to determine whether to advance the triple or not.

Liz Shea, Vice President of Investor Relations

All right, thanks Matthew. Thanks, Mike. Operator, next question please.

Operator, Operator

Thank you. Our next question is from Steve Scala with Cowen. Your line is open, sir.

Steve Scala, Analyst