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AbbVie (ABBV -0.76%)
Q3 2020 Earnings Call
Oct 30, 2020, 9:00 a.m. ET


  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:


Good morning. And thank you for standing by. Welcome to AbbVie's third-quarter 2020 earnings conference call. [Operator instructions] I would like to introduce Ms.

Liz Shea, vice president of investor relations.

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. 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 1995. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties including the impact of the COVID-19 pandemic on AbbVie's operations, results, and financial results 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 2019 annual report on Form 10-K and in our other SEC filings. AbbVie undertakes no obligation to update these forward-looking statements except as required by law. On today's conference call, as in the past, non-GAAP financial measures will be used to help investors understand AbbVie's ongoing 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 operational basis, which includes the full-current year and historical results for Allergan, and excludes the impact of exchange. For this comparison of underlying performance, all historically reported Allergan revenues have been recast informed to conform to AbbVie's revenue recognition accounting policies and exclude the recent divestitures of Zenpep and Viokace. Following our prepared remarks, we'll take your questions. So with that, I'll now turn the call over to Rick.

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Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Thank you, Liz. Good morning everyone. And thank you for joining us today. I'll discuss our third-quarter performance and highlight as well as our full-year guidance which we are raising again this quarter.

Mike will then provide an update on recent advancements across the R&D programs, and Rob will discuss the quarter in more detail. Following our remarks, we'll take your questions. AbbVie delivered another excellent quarter with adjusted earnings per share of $2.83 exceeding the midpoint of our guidance range by $0.08. When I look at our business and the actions we've taken the position, AbbVie for sustainable performance including the acquisition of Allergan, I feel very good about our long-term outlook.

The fundamentals are strong and there is considerable momentum across our legacy and new portfolios which are both demonstrating robust growth despite the COVID endemic, and together have the potential for significant long-term value creation. I'd like to specifically highlight our recent progress across several aspects of our business, including the launches of Rinvoq and Skyrizi which are performing well ahead of all comparable launch analogs in their initial indications and continue to exceed our expectations. Our hem/onc franchise also continues to deliver robust performance and is expected to generate more than $6.5 billion in revenue this year representing strong double-digit growth. New indications and novel combinations including our recently announced collaboration with Genmab and I-Mab provide opportunities for further revenue expansion.

While we're still relatively early in the integration of Allergan, the strategic merits of the combination have never been more evident. We're already demonstrating that we have created a stronger, more diverse company with robust cash flows, and multiple new growth vehicles for the long term. We now have the leading and statics franchise which is demonstrating a strong V-shape recovery, as well as a highly attractive neuroscience portfolio that delivered double-digit growth on a comparable operational basis this quarter and has significant momentum with Vraylar and our expanding migraine franchise. And our pipeline is advancing nicely with numerous, attractive late-stage programs that we believe will allow us to maintain a growing and vibrant business.

We're on track for the approval of more than a dozen new products or major indications over the next two years, which will collectively add meaningful revenue growth. This includes a total of six additional indications the Rinvoq and Skyrizi expanded indications for Venclexta and several other near-term products -- new product approvals, including atogepant, Venetoclax, and 951. Clearly, this is a very exciting time for AbbVie, and I'm pleased with the progress that we're making toward our long-term strategy for sustainable growth. I remain confident that we will continue to execute as we have in the past, and deliver outstanding shareholder value going forward.

I'd like to look further at our business performance. I'm pleased with the recent trends across our key growth areas. I'll start with immunology where we establish strong trajectories for Rinvoq and Skyrizi. As I previously noted, both continue to perform well above expectations in their initial indications.

These two brands have clearly demonstrated superior efficacy in Humira, as well as other novel agents on the market or in development resulting in significant in-play market shares a leading indicator for long-term commercial performance. The in-place share Rinvoq and Ubrelvy which includes both new and switching patients remain strong at approximately 16% and have now reached parity with our market-leading Humira. In psoriasis, Skyrizi has already achieved the leading in play market share at 33%. This level of share capture at this stage of the launch is unprecedented, and if sustained will ultimately lead to a total market share well in excess of what was contemplated when we communicated our expectations for 2025 sales.

This strong performance and trajectory despite the impact of the COVID-19 pandemic is a testament to our differentiated product profile and our commercial execution. Our focus on the pandemic has been on driving accelerated patient activation, and we remain encouraged by our current prescription trends. Our recent performance continues to give us confidence in the near and long-term potential for both Rivoq and Skyrizi which we now expect will deliver $2.2 billion in combined revenue for full-year 2020. Well exceeding our original projections for this year.

In addition to outstanding commercial momentum, we're also making excellent progress with Rinvoq and Skyrizi in new indications, which we expect will further strengthen our leadership position. We have already started playing and preparing for the forthcoming approval of three additional Rinvoq indications next year, including psoriatic arthritis and ankylosing spondylitis. Giving us complete coverage across the more than $40 billion Rheumatology segment. We also expect approval in atopic dermatitis, another large and growing market that has the potential to be multi-billion-dollar peak revenues for Rinvoq.

In the coming year, we also intend to submit regulatory applications for Skyrizi in psoriatic arthritis and both agents in the area of inflammatory bowel disease, a more than $20 billion market today with high unmet need. Overall, I'm extremely pleased with the progress we're making on both Rinvoq and Skyrizi. I'd also like to take this opportunity to announce that we will be hosting an immunology-focused Investor Day in December, where we intend to further discuss our strategy, progress, and expectations for this important growth area. Additional details will be forthcoming.

Turning now to Genmab, which delivered robust double-digit growth again this quarter, and remains an important therapeutic area grab these long-term performances. Imbruvica has a strong position across multiple indications, including CLL where it remains the clear market share leader across all lines of therapy. Imbruvica sales increase 9% on an operational basis this quarter despite lower new patient starts within CLL where the market remains below pre-COVID levels. Venclexta sales increase by nearly 60% on an operational basis this quarter. The penetration across our approved indications remains strong especially in AML given the potential aggressive disease progression of that cancer.

In the quarter, we also announced a strategic collaboration with I-Mab further expanding our oncology portfolio with the anti-CD47 monoclonal antibody which has potential across a wide range of blood cancers. The I-Mab opportunity adds to our already attractive oncology pipeline which includes Venetoclax, Genmab CD3xCD20, expanded indications for Venclexta, and several promising early stage programs. We also now have another high-performing franchise in neuroscience which further diversifies at these sources of long-term growth. Vraylar sales increase strong double-digits again this quarter on a comparable operational basis with annualized revenues of more than $1.4 billion.

Given Vraylar benefit-risk profile relative to other atypical antipsychotics, we remain confident in its long-term growth potential which we believe is multi-billion dollars across the currently approved indications of bipolar disorder, and schizophrenia. Botox Therapeutics which has nearly a dozen medical treatment indications, including chronic migraines is also performing very well. Revenues were up nearly $100 million sequentially on a comparable operational basis demonstrating a rapid COVID recovery. The launch of Ubrelvy, our leading oral CGRP for acute migraines is exceeding our expectations.

Commercial access is ramping strongly and increasing DTC investments have resulted in encouraging new patient starts and market expansion. When you consider, our overall scale with Botox Therapeutics, Ubrelvy's acute treatment profile, and the promising development of atogepant for the prevention of episodic and chronic migraines, we see substantial room for long-term revenue growth with this best in class migraine portfolio. Within aesthetics, our fourth major growth platform we're seeing robust demand trends in rapid V-shape recovery. Total global aesthetics revenues of more than $950 million, or up 70% sequentially on a comparable operational basis illustrating the significant underlying demand for both Botox Cosmetic and Juvederm.

We remain focused on supporting clinics through the COVID pandemic and expect consistent investment in consumer promotion to expand the aesthetics market which remains under-penetrated globally. Our dedicated R&D and business development are expected to sustain new innovation and rapidly expand our aesthetics portfolio for long-term growth. Including the recently announced acquisition of Luminera, which provides us with a complimentary dermal filler portfolio and pipeline. Overall, we're very pleased with the momentum that we're seeing with our aesthetics franchise. AbbVie's business continues to remain resilient and demonstrates strong underlying growth throughout the pandemic.

Based on the performance this quarter and our progress year to date, we're raising our full-year 2020 EPS guidance. We now expect adjusted earnings per share of $10.47 to $10.49, reflecting growth of more than 17% at the midpoint. In addition to the excellent progress, we're making across the portfolio, the integration of Allergan continues to go very well. Despite the size of this transaction and the timing of the COVID pandemic, the transition has been seamless.

We're performing very well against both our synergy and accretion targets, and it has become increasingly clear to us that there are also opportunities for revenue synergies across various aspects of the business. We're now six-months post-close and the strategic merits of the transaction are extremely evident. Allergan providing additional growth platforms, robust financial benefits, and greater diversity of our business. We remain confident that the newly combined business will generate significant earnings and cash flow to support continued investment in our innovative R&D platform, as well as a strong and growing dividend, while also allowing us to rapidly pay down debt.

To that end, as noted in our news release, today we're announcing a 10.2% increase in our quarterly cash dividend. From the $1.18 per share to $1.30 per share beginning with the dividend payable on February 21. Since inception, we have grown our quarterly dividend by 225%. So in summary, we continue to demonstrate strong execution across our portfolio and remain encouraged by the overall recovery trends.

We've assembled an impressive set of diversified growth assets with significant growth potential giving us a high degree of confidence in the long-term outlook for our business. With that, I'll turn the call over to Mike.

Mike Severino -- Vice Chairman and President

Thank you, Rick. We continue to make great progress across all stages of our pipeline. And this morning, I'll highlight key events since our last earnings call. Starting with immunology where we achieved several major milestones, including submission of our U.S.

and European regulatory applications for Rinvoq ankylosing spondylitis and atopic dermatitis. We expect regulatory decisions in the first half of 2021 for both indications, as well as for psoriatic arthritis which was submitted for regulatory review earlier this year. Within the Rheumatology segment, both psoriatic arthritis and ankylosing spondylitis are large and important markets and represent a significant growth opportunity for Rinvoq. We will highlight the growing body of data from our rheumatology portfolio, and the -- at the upcoming virtual ACR Congress where we will present 35 abstracts from multiple assets across our portfolio, including six selected for oral presentation.

Atopic dermatitis is a new disease area for AbbVie, and also represent an important area of growth for our immunology franchise going forward. Based on the data generated in our registration program, we remain very confident in the benefit-risk profile for Rinvoq and atopic dermatitis, and believe it will offer meaningful advantages of our products on the market today or in development. Beyond the Phase 3 studies that support our regulatory submission, we are also evaluating Rinvoq in a head-to-head Phase 3 trial against dupilumab which if successful will help further support Rinvoq as a highly differentiated therapeutic option for patients with atopic dermatitis. We look forward to seeing data from this head-to-head study later this quarter.

In the area of inflammatory bowel diseases, we remain on track to see induction data later this quarter from our Phase 3 program for Rinvoq and ulcerative colitis. We'll see data from a second induction study in ulcerative colitis, as well as results from the maintenance portion of these studies next year. We expect to file our regulatory applications in 2021 as well. We are also making great progress with the development programs for Skyrizi.

And later this quarter, we expect data from several new indications across rheumatology and gastroenterology. We'll see data from 2, Phase 3 studies in psoriatic arthritis, and results from the first Phase 3 induction study in Crohn's disease supporting regulatory applications for both indications in 2021. Outside of immunology, Skyrizi will also be evaluated as a potential treatment for COVID-19 as part of the NIH Activ program which is a public-private partnership aimed at accelerating potential therapies and vaccines for COVID-19. Skyrizi was selected through a prioritization process that evaluated immunomodulators with acceptable safety profiles as potential treatments for COVID-19 complications caused by the cytokine storm observed in some patients.

Skyrizi will be included in the Activ5 big effect trial which is a Phase 2 study designed to evaluate a number of drugs that are either approved or in late-stage development as potential treatments for COVID-19. In our early stage immunology pipeline, earlier this year, we top-line positive results from a proof of concept study evaluating our novel TNF steroid conjugate, ABBV-3373 in RA. We recently completed the Phase 1 PK and safety study for our second TNF steroid conjugate, ABBV 154. Based on these data, we have selected 154 to move forward into large-scale trials. We expect to begin a Phase 2b definitive dose-ranging study for 154 in RA in the first half of 2021.

As Rick mentioned, we will be hosting an Immunology Day for Investors in December where we will provide an update on our immunology strategy and long-term outlook for the franchise. We look forward to providing additional updates on our immunology pipeline at that time. In oncology, we continue to advance our portfolio with several important Phase 3 studies beginning in the quarter, including in high-risk Myelodysplastic syndrome, and Venetoclax in myelofibrosis. We also recently received full FDA approval of Venclexta in combination with azacitidine or decitabine, or low-dose cytarabine, a newly diagnosed AML patients who are ineligible for intensive induction chemotherapy.

This approval is supported by the Phase 3 VIALE-A, and VIALE-C studies. Updated efficacy and safety results from VIALE-A were recently published in The New England Journal of Medicine and show that the combination of Venclexta and azacitidine extended overall survival, compared to azacitidine placebo. Additionally, following the publication of the VIALE-A results the NCCN guidelines were updated to recommend the Venclexta and azacitidine combination as a Category 1 preferred treatment for AML patients who are ineligible for intensive chemotherapy. Importantly, the Venclexta combination has the Category 1 designation irrespective of mutational status.

Also in the quarter, we announced a collaboration with I-Mab to develop and commercialize the Anti-CD47 monoclonal antibody, lemzoparlimab. The emerging data for lemzoparlimab is very encouraging and provides AbbVie access to another potentially differentiated asset in the Immuno oncology space. The data generated today show that lemzoparlimab effectively blocks tumor-specific CD47 interactions, but with much lower binding to red blood cells potentially leading to a better safety profile. Lemzoparlimab is being studied in multiple cancers with a focus on hematological malignancies.

In neuroscience, we recently presented new data from several clinical programs at the virtual Migraine Trust International Symposium showcasing the breadth and strength of our migraine portfolio and demonstrating AbbVie's commitment to providing multiple treatment options for the acute and preventative treatment of migraine. In total, 15 abstracts were presented for Botox, Ubrelvy, and atogepant. Included in the MTIS presentation were the detailed results for atogepant in the Phase 3 advance study which demonstrated a clinically meaningful and statistically significant improvement over placebo. With all atogepant doses for the primary endpoint of reduction in mean monthly migraines days.

Significant improvements were also observed for all secondary endpoints in the 30-milligram and 60-milligram dose groups. Treatment with atogepant resulted in 56% to 61% of subjects achieving at least a 50% reduction in monthly migraines days, compared to 29% for the placebo group. We're very encouraged by the strong benefit-risk profile that has been demonstrated for atogepant in migraine prevention, and believe that once approved this new oral treatment option will be competitively position in the prevention market. Together with Botox for chronic migraines prevention, and Ubrelvy for acute migraines treatment the addition of atogepant creates a market-leading portfolio in migraines that represents significant long-term value for AbbVie.

In aesthetics, we continue to make good progress with our portfolio of facial toxins and dermal fillers. We have several ongoing programs for new indications for Botox and for the Juvederm collection, as well as a pipeline of innovative toxins and dermal fillers which we expect to reach the market over the course of the next five years. Botox has been the leading neurotoxin for over two decades with R&D efforts in aesthetics primarily focused on the upper phase. To support expansion to the lower phase region, we have several programs ongoing, including studies in masseter and platysma ProMax.

We recently had a positive data readout for our Phase 2 study for the reduction of masseter prominence in the lower phase. This study met all primary and secondary endpoints demonstrating that the severity of prominence was reduced following a single treatment of Botox. Based on these results, we plan to begin Phase 3 development next year which will support registration in the U.S. and Europe.

We also recently announced the acquisition of Luminera's dermal filler portfolio led by HArmonyCa which is an innovative dermal filler developed for facial soft tissue augmentation. Luminera's assets are highly complementary to our Juvederm filler franchise, and we look forward to expanding their development to markets around the world. And in eye care, we recently announced positive top-line results from the Pase 3 Gemini 1, and Gemini 2 studies which evaluated our topical eye drop AGN-190584 for the treatment of symptoms associated with presbyopia. In both studies, 584 met the primary endpoint and the majority of secondary endpoints.

Data from both studies demonstrating that treatment with 584 resulted in significant near vision gains in low lighting conditions without a loss of distance vision. Based on these results, we plan to submit our regulatory application to the FDA in the first half of next year. So in summary, we continue to make significant progress advancing and accelerating our programs this quarter, and we look forward to many more important pipeline milestones in the coming months and through 2021. With that, I'll turn the call over to Rob, for additional comments on our third-quarter performance and financial outlook.


Rob Michael -- Executive Vice President and Chief Financial Officer

Thank you, Mike. Starting with third-quarter results. We delivered strong top and bottom-line performance. We reported adjusted earnings per share of $2.83, above our guidance midpoint by $0.8.

Total adjusted net revenues were approximately $12.9 billion, up 4.1% on a comparable operational basis and ahead of our expectations. Immunology global sales were approximately $5.8 billion, up 15% on an operational basis. Despite the impact of COVID, our new patient starts across the immunology market. U.S.

Humira sales were approximately $4.2 billion, up 7.7% compared to the prior year reflecting continued demand growth plus the price. Wholesale inventory levels remain below half a month in the quarter. International Humira sales were $951 million, down 8% operationally reflecting biosimilar competition across Europe and other international markets. Skyrizi sales were $435 million with leading in-play share in the US psoriasis market, and robust sequential growth internationally.

Rinvoq sales were $215 million with continued strong in-place share in the U.S. RN market. Hematologic Oncology delivered another strong quarter with sales of $1.7 billion, up16.4% on an operational basis. Imbruvica net revenues were approximately $1.4 dollars, up 9% driven by our leading share in CLL.

Venclexta revenues were $352 million with strong demand across all approved indications. Mavyret sales were $414 million, down 41.1% on an operational basis, as treated patient volumes have remained below pre-COVID levels. Aesthetic sales were $967 million with Botox Cosmetic and Juvederm both experiencing a faster than expected recovery from the COVID pandemic. Neuroscience revenues were more than $1.2 billion led by Vraylar and our migraine portfolio.Vraylar once again delivered strong growth with revenues of $358 million.

Botox therapeutic continues to experience a rapid recovery from the COVID pandemic with sales of $523 million in the quarter. The launch of Ubrelvy is also going very well with the recent direct-to-consumer promotion driving new prescription growth. Sales of Ubrelvy were $38 million. We also saw a significant contribution from eye care which had sales of $840 million.

Turning now to the P&L profile. For the third quarter, the adjusted gross margin was 81.7% of sales. Adjusted R&D investment was 11.7% of sales, and adjusted SG&A expense was 21.1% of sales. The adjusted operating margin ratio was 48.8% of sales, an improvement of 40-basis-points versus the prior year.

Net interest expense was $620 million, and the adjusted tax rate was 11.7%. As Rick previously mentioned, we are raising our full-year adjusted earnings per share guidance to between $10.47 and $10.49, including accretion from the Allergan transaction of 1% on an annualized basis. Excluded from this guidance is $6.58 of known intangible amortization and specified items. This guidance now contemplates 2020 adjusted net revenue of approximately $45.7 billion, representing an increase of $200 million from our previous estimate.

At current rates, we now expect foreign exchange has a modest unfavorable impact on full-year report sales growth. Included in this guidance are the following updated 2020 assumptions: we now expect internationally Humira sales approaching $3.7 billion; for Skyrizi, we now expect revenues of approximately $1.5 billion; for Rinvoq, we now expect sales of approximately $700 million; for Imbruvica, we now expect revenue of approximately $5.3 billion as the new patient starts in the CLL market remain below pre-COVID levels; for aesthetics, we now expect post-close sales of approximately $2.5 billion; with Botox Cosmetic and Juvederm, both demonstrating a fast recovery; for Mavyret, we now expect sales of approximately $1.9 billion, as treatments remain below pre-COVID levels; we now expect Lupron revenues of approximately $750 million, as we work to resolve a near-term supply issue which is impacted the availability of certain formulations. Moving into P&L. We continue to forecast a full-year adjusted gross margin just above 82% of sales, and an adjusted operating margin of approximately 48% of sales.

This guidance includes approximately $600  million in expense synergies for the partial year in 2020. We remain on track to deliver greater than $2 billion in expense synergies by 2022. As we look ahead to the fourth quarter we anticipate adjusted net revenue approaching $13.8 billion. At current rates, we expect foreign exchange to have a modest favorable impact on unreported sales growth.

We are forecasting an adjusted operating margin ratio of approximately 46.5% of sales. We model a non-GAAP tax rate of 11.6%, and we expect the average share count to be similar to Q3. We expect adjusted earnings per share of between $2.83, and $2.85 excluding approximately $1.73 of known and amortization and specified items. Finally, AbbVie's strong business performance continues to support our capital allocation priorities.

We generated $12.7 billion of operating cash flow in the first nine months of the year, and our cash and investment balance at the end of September was $8 billion. Underscoring our confidence in Abby's long-term outlook, today, we announced a 10.2% increase in our quarterly cash dividend beginning with the dividend payable in February 2021. We also remain on track to pay down $15 billion to $18 billion of combined company debt by the end of 2021 and expect to achieve a net debt to EBITDA ratio of 2.5 times by the end of next year with further deleveraging through 2023. 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. Operator, first question, please.

Questions & Answers:


Thank you. [Operator instructions]. And our first question today is from Chris Schott from JP Morgan.

Chris Schott -- J.P. Morgan -- Analyst

Great. Thanks, so much for the questions. And congrats on the results. I guess just two for me.

First, 2021 I know you're not giving guidance yet. Can you talk through some of the pushes and pulls we should keep in mind as we think about next year's numbers. It seems like the core business of this is a lot of traction here. I'm just trying to get a sense of [Inaudible]from your perspective.

What are the uncertainties you think about that, that guidance number for next year. And my second question was on Rinvoq in atopic derm. Can you just elaborate a bit more on how you're thinking about the size of that opportunity. I know one of your peers has a single indication, JAK, and AD, they think it's a $3 billion peak sales opportunity.

I know that's well above your risk-adjusted, just the numbers you have a few years ago it sounds like now you're talking about a potential multibillion-dollar opportunity. But just help us flesh out a little bit about how big of an opportunity could this be for the product. Thank you.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

OK. So, Chris, this is Rick. I'll talk a little bit about 21, and then Mike maybe you can talk a little bit about how we view window Rinvoq  A&D and Rob. So when we look at 21, I think you have to step back and say "how are we performing this year".

And obviously, we're performing very well. There's still some COVID impact built-in. It varies a bit by therapeutic area. Some areas are impacted more than others.

So as an example, CLL has been impacted more than other areas. HCV has been impacted more than in other areas. It usually places where the therapy can be delayed without significant consequence, or the patient is where we're seeing the most significant delays. So, as we move through the fourth quarter, we'll see whether or not that will cover more.

And that's certainly one aspect of it. I would say even without much recovery the underlying performance of the business looks good. I think you can look at the dividend increase that we put through, and that should give you some flavor for the level of confidence that we have. Because obviously, we want to tie that to what we assumed that we could deliver from an overall performance standpoint.

I'd also say that as we've looked at consensus, we're comfortable with what we see and consensus in 2021. So we will see a few other things just play out primarily around COVID and how much improvement we get. We have launched a number of programs over the course of the last couple of months to try to activate patients more to go to their physicians and seek treatment out. I think those programs, some of those programs will be successful and we'll see some of those increase particularly in immunology.

Because dermatology is another one of those areas that the new patient starts are still awful a little bit. That obviously Skyrizi is performing extremely well and the Humira teams to perform well. So I'd say that's the single biggest issue. Mike might want to talk about Rinvoq's.

Mike Severino -- Vice Chairman and President

Certainly. I'll start and then pass it over to Rob if he wants to add a little bit more detail. We view atopic dermatitis as a very attractive, and a very substantial opportunity. Overall, it's an indication that I think for many years was underappreciated by the industry.

Now that's changed recently. And you've seen a lot of focus on drug development and atopic dermatitis. We feel very good about the profile that we've demonstrated. Coming out of Phase 2 when we made those statements about the risk-adjusted potential in atopic dermatitis, we felt good about our data.

And those data were sufficient to get a breakthrough therapy designation. We're in the fortunate and not always that common situation where our Phase 2 results have actually outperformed our expectations based on Phase 2. And if you look at the Phase 2 results are really strong across the board. They're strong in total response.

They're strong in the rapidity of response, and they're strong on components like an itch which is the most troublesome symptom to patients in the majority of cases. And so when you couple that with the safety profile that we've demonstrated which we think is very favorable. We see this as something that has very real potential. And when we look at across studies, we feel very good about our results and of course, we have a head-to-head study with dupilumab which is coming up later in this quarter.

And so that will be important additional information and we're very optimistic about those results. Right now, I don't know if you'd like to add anything further.

Rob Michael -- Executive Vice President and Chief Financial Officer

Hi, Chris. This is Rob. So if you think about atopic dermatitis it's a $3 billion global market with very strong growth potential. And our 2025 risk-adjusted guidance of great income going for Rinvoq and Skyrizi we included a billion dollars of revenue for Rinvoq AD.

Well, we feel pretty good that we could achieve that expectation. 

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

And the only other thing I add is, I think the topic dermis a market very similar to several others. In fact psoriasis, I would say was a similar type of market that as you get more competitors in the market driving promotion, it has a very large population of patients. So the question is activating those patients and getting them to go into the physician's offices to seek treatment. And so obviously, when you have one company doing that, they have the capacity to drive a certain amount.

When you have more than one company, you're doubling or tripling the amount of promotion activity particularly here in the U.S. And that tends to activate more patients to seek treatment. I think if you looked at the total available Mavyret patients who would qualify, it's a huge market. It's north of $5 billion easily.

So the question is how fast can you activate them, and how broadly can you activate those patients. From a profile standpoint of our drug.I think we'll compete quite effectively. And I think in particular the performance around it she's going to give us an advantage. So it's a very attractive market, and certainly, one that we will focus a lot of attention on we could drive.

Rob Michael -- Executive Vice President and Chief Financial Officer

Hi, Chris. This is Rob. And just to clarify, I'm not sure I said exceed or achieve a week. I expect to exceed that billion-dollar risk-adjusted number for Rinvoq AD in 2025.

Liz Shea -- Vice President of Investor Relations

Thanks, Chris. Operator, next question, please. 


Thank you. Our next question is from Geoffrey Porges from SVB Leerink.

Geoffrey Porges -- SVB Leerink -- Analyst

Thanks. With the dividend going up it looks like you've got about a 6.5% dividend yield. The core business of the polling well. And my question is what are -- and now $50 billion to $55 billion top line company.

What are the pipeline assets that can really move the needle? I know all the new indications of the existing NMEs, but what new NMEs can be really substantial to move the needle on a $55 billion top line. Because I think that's part of why you've got the industry high dividend yield.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

So, Geoff, this is Rick. I think if you look at the business, you have to look at it in phases, right. So I'd say the phase between now and call it 2025, 2026 that growth is going to be driven by the expansion of Rinvoq and Skyrizi continued strong growth in the neuroscience pipeline. Continued strong growth in the aesthetics pipeline, and continued strong growth in [Inaudible].

Starting on that 25 timeframes and beyond that's where the earlier to mid-stage pipeline will drive a significant amount of growth. Now there will be assets like Venetoclax, like 951, atogepant that will come in prior to that and help boost growth right around 23 and 24. I can tell you, we're very confident that we have now built a portfolio that can sustain growth and drive growth on the other side of the ROE. In fact, I would tell you that when I look at Rinvoq and Skyrizi, and I look at the in-play market shares that we see with those assets.

Today, when we gave guidance for 2025, we assumed that on average we will achieve a high single-digit market share across the indications. So as an example, if you look at Skyrizi right now, Skyrizi is in place shares 33%. The market leader by a wide margin. The next closest product is at 16% in place share.

And its TRX share is now at 11% and climbing rapidly. So it's already above what we had assumed the peak would have been out in 2025 from a market share standpoint. And if we maintain that 33% by then, it will have an overall share of about 33%. So it will be three times what we had assumed for psoriasis.

So when you look at the speed at which we're bringing the new indications. When you look at the breadth of those indications across the revenue base that you Humira has today, we have covered all of the major indications for Humira, plus one more Humira doesn't have which is atopic derm. And if we can achieve that kind of market share in each of these indications, then we'll obviously, double what we assume that 2025 number was. And that gets you pretty close to covering all of Humira in the US.

So, I'm very encouraged about that, and I think that along with the other assets and the four major growth platforms gives us a tremendous amount of confidence that we can drive growth on a sustainable basis at a very, very high level.

Liz Shea -- Vice President of Investor Relations

Thanks, Geoff. Operator, next question, please.


Thank you. Our next question is from Vamil Divan from Mizuho Securities.

Vamil Divan -- Mizuho Securities -- Analyst

Thanks so much for taking my question. So maybe just to start pulling up about one thing after 2020, we are all now because of this question. Can you just talk a little bit -- do you think about drug pricing pressure in the U.S. or globally.

Just beginning to shrink. Think about modeling for next year that would be helpful. And then maybe building on Geoff's question. I think one of the other concerns that investors have is around potential tax reform that may come out of D.C.

depending on the election plays out. It's tough to assess it a few days before the election. But I guess based on what you're seeing from the -- especially from the Biden side. I get the Biden plan right now.

Is there anything you can share with investors at this point in terms of how your tax rate may change going forward? It's not much to me but these are things that I think would be helpful. I think it is, I mean investors seem very concerned about at this point. Thank you.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Well obviously, it's still unclear as to what the landscape will be on the other side of the election. So we obviously have to let that play out. Having said that, I think we assume that there will be continued pressure on the industry as it relates to drug pricing. As far as what our expectations would be in 2021 of the great expectations in 2021 from a price standpoint will be similar to what they were in '19 and '20.

And that is we weren't reliant on price. Unfortunately, our business is primarily a volume driven business. It's typically in areas that are very serious diseases and have strong value propositions. And so that gives me confidence that we'll be able to fare reasonably well even if there are changes.

I'd say the second thing is, it's unlikely that you will get changes that have a significant impact early on in '21. Because there's going to be a lot of debate here about what those changes are. What I would hope the debate ultimately transitions to is co-pays and out-of-pocket costs for the patients because that is the fundamental issue. And particularly the issue when you look at part D patients, they have to pay far too much of the burden of the cost from an out of pocket cost standpoint.

And they're really the only group of patients in the US that have that kind of a burden associated with them. If you look at the overall performance from a cost standpoint of Medicare Part D, it's performed very well. If you go back to the original CBO estimates over the last 10 years it's come in 45% below the original estimates for what we grow. And if you look at part D, it's growing at about the rate of other healthcare services inflation not to get significantly higher.

And so the affordability problem is really around those co-pays that we have to drive those co-pays. And then I think the other thing that has to be played here is, I would hope as this debate goes on they're going to look very carefully at our industry and the value of our industry, both from a societal standpoint as well as an economic standpoint. And this is a tremendously valuable industry. Just look at what we've done as an industry as it relates to this pandemic, whether you're talking about vaccines, or you're talking about therapeutics.

Look at what we've done in advancements with cancer. And then from an economic standpoint, this industry supports directly or indirectly 4 million jobs in the United States, typically high paying jobs. It produces a tremendous amount of economic output for the US. And so it's an industry that you don't want to damage in the process and I think that's part of the debate.

But the short answer to your question is, I think you should --we are not assuming. We get a lot of benefit from the price in '21. We're also not assuming that across that year we would see a significant change that would have a dramatic impact on that calendar year. Tax reform is your next question.

Mike Severino -- Vice Chairman and President

[inaudible]Based on a very high level of information in the Biden proposal, we would see an increase in our tax rate like most U.S. companies. But it's really difficult to provide a rate impact without the details. That said, AbbVie would still have a favorable profile versus our peers, and we want to have raised our dividend if we were overly concerned about the implications.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

And the only thing I would add on Vamil on that one is we obviously, did flex what we thought the tax rate could be. And we just don't know that much about it. We know what has been said. But we flexed it against this dividend increase and made sure we were absolutely comfortable with payout ratios based on that.

And we are very willing to move forward with a 10.2% increase.

Liz Shea -- Vice President of Investor Relations

Thanks, Vamil. Operator, our next question, please.


Thank you. Our next question is from Steve Scala from Cowen.

Steve Scala -- Cowen and Company -- Analyst

Thank you, so much, and congratulations on another impressive quarter. I have several questions, but three of them are short. Can you be more specific on where Skyrizi patients are coming from? I think it's notable that COSENTYX was a bit light this quarter, and Novartis cited competition. Secondly, what was the non-GAAP interest expense number in the quarter? Third, you provided guidance for Humira OUS, but I don't think the U.S.

So can you tell us what you think the U.S. guidance would look like. And then lastly, we have tracked clinical trial activity during the pandemic and it shows AbbVie recruiting trials are up 14% year to date. That is industry-leading two times greater than the next closest competitor and much better than the average which is down.

And I'm just curious what accounts for this. Is it a deliberate strategy to capture patients when other companies are taking a wait and see approach, or is it something else? Thank you.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

So, Steve, I'll handle your first question. Rob, will handle two and three, and Mike will handle No. 4. So if you look at the end play share about 25% of that in play share is coming on Skyrizi is coming from Humira.

The other 75% is coming from competitors. I'd say it's primarily the seven teams, but some coming from the other 12, 23's, or 23's. But I'd say the bulk of it is coming from the seventeens. So that might answer your question about COSENTYX.

If you look at the capture of the type of patient that we're getting at Skyrizi, it's very balanced. It's about 50/50 between the first line, and then the second line. So that's a nice balance between 90 patients and patients who have failed other therapies. So, I think it's the asset is performing the way you would expect a high performing, high efficacy asset to be able to perform is it has quickly become the preferred product by prescribing physicians.

It has a great profile. It's a quarterly dosing. It's got great efficacy, the efficacy improves over time. There are any assets that have a profile on the market.

So, I would expect it that Skyrizi will continue to increase its in-play share. It jumped about three points over the last maybe two months. And I would expect it will continue to increase.

Rob Michael -- Executive Vice President and Chief Financial Officer

Steve this is Rob. On your question on interest expense. For non-GAAP and GAAP, it's the same number at $620 million in the third quarter. We're no longer specifying any interest expense because we've now closed the transaction, so that negative carry on the bonds no longer applicable for the specified.

So $620 million is the number for both non-GAAP and GAAP. On the U.S. Humira question. So we did not change our guidance because it continues to be -- for U.S.

Humira, 8% growth with a low-single-digit price contribution.

Mike Severino -- Vice Chairman and President

This is Mike. I'll take your last question on clinical trial activity. The first thing that I would say is the increase in clinical trial activity reflects what's going on in our pipeline. And there's a lot of activity in our pipeline, and a large number of molecules that we're advancing.

And so that's a big part of it. Another part is that we made the conscious decision to leave decisions around enrollment in the hands of investigators, rather than making them centrally because they understand the situation in their hospital and their community better than we do. And there was a small group of studies that we paused at the time of the initial COVID impact, but the majority, we allowed to continue. That doesn't mean that there weren't disruptions from COVID.

But it does mean that investigators decided when it was time to pause enrollment and when it was time to resume enrollment. And I think the evidence shows that they made those decisions better than they could have been made centrally. And that has allowed us to advance our portfolio, to advance our clinical trials with minimal disruption and with safe conduct for our patients and the staff of the site which are also critically important considerations. And so I'd say, it's a combination of those factors.

Liz Shea -- Vice President of Investor Relations

Thanks, Steve. Operator, next question, please. 


Thank you. And our next question is from Naveen Jacob from UBS.

Naveen Jacob -- UBS -- Analyst

Hi, This is [Inaudible] for Naveen Jacob. We just had a few questions. First, regarding the Humira flex in the US within the markets in which a biosimilar is out there. What percent of the molecule is now brand versus biosimilars with now almost two years, with now almost two years of biosimilar experience, how does that affect things? And next for Skyrizi and Rinvoq, can you achieve the type of uptake that you have been seeing in the US in the international markets.

We'd appreciate and commentary around in the play and market share achieved in markets you've been approved in. And lastly, if we could talk about Vraylar MDD timing. Thank you.

Rob Michael -- Executive Vice President and Chief Financial Officer

This is Rob. Just to clarify the first question was on international Humira. How much of that is now a biosimilar.

Naveen Jacob -- UBS -- Analyst

Right. Within the markets whether it's by a similar. How much is brand versus biosimilar to help us visualize that question?

Rob Michael -- Executive Vice President and Chief Financial Officer

The ones with the smaller with them all sorted. Yes. We're at about 60% molecules share across the board. So that's all the international markets on average is about 60% molecule share.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Then Skyrizi and Rinvoq. I don't have the numbers right in front of me on each of the markets. I would say typically, in the international market it is a slightly slower uptake than it is in the US, but still doing very well. So maybe the best thing would be to get back to you with some more specifics around that.

But I think you can assume that the in-place share there probably averages between 20% and 30%. But it depends. Obviously, on the country that you're talking about. And then Vraylar MDD timing.


Mike Severino -- Vice Chairman and President

Yes. On Vraylar MDD, we'd expect to have the study's readout in the second half of next year and be prepared for regulatory submissions shortly thereafter. So it possibly would have approval in '22.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

I think that's an important point to make here. If we look at Vraylar, Vraylar was growing very rapidly. And as you know, the atypical antipsychotic market is very, very large. I think Vraylar shares it's something like 3%, and it's tracking at $1.4 billion at 3%.

So if we look at the current indications as we indicated in the comments of bipolar and schizophrenia, we think we can drive Vraylar alone and those indications to a multi-billion dollar product. And that's just driving that market share penetration up like 5% or so. And I think that's very doable based on the profile of Vraylar. Vraylar is a very unique profile in that market.

So MDD if we're successful. Obviously, will open up a whole nother channel and allow you to increase that market share even more significantly. And so typically many of the drugs they achieve MDD were drugs they had $5 billion, $6 billion of annual revenue. This is it.

This is a nice opportunity without MDD, Vraylar is still can be a very important product, and a very significant product. With MDD it becomes a major product. And so, we'll see how those next two studies play out. The first study was positive, and I think we're hopeful that we'll be able to get.

Liz Shea -- Vice President of Investor Relations

Thanks, Rick. I think that was you. Operator, next question, please. 


Thank you. Our next question is from Randall Stanicky from RBC Capital Markets.

Randall Stanicky -- RBC Capital Markets -- Analyst

Great. Thanks. Rick, early in the pandemic you're one of the few to identify or building impact for potential headwinds from higher unemployment associated with loss of health coverage. What are you currently seeing right now? And anything on the patient assistance program numbers that help you inform on that.

And then secondly, I just want to ask about Botox migraine. This has been historically a roughly $600 million high margin product for Allergan. We've been watching the CGRP impact did in the market a couple of years. Do you see this as a growth product opportunity for you and what are you seeing overall with respect to Botox migraine? thanks.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

On the unemployment, we did identify back. I guess it was in the first-quarter call that we were going to build in a level of risk associated with patients who would have to move to some type of assistance program because they lost their jobs. We have not seen that impact play out to any significant level. We have not seen it in our Patient Assistance Program.

And right around the pandemic, we made a decision to proactively go out and advertise our Patient Assistance Program just to make sure that patients knew that if they couldn't afford their AbbVie drugs that they could get them from us. So I think, we proactively tried to drive it in an effort to make sure that patients were not exposed. But we haven't seen very much at all. We still have some coverage left in the fourth quarter for it.

But I'd say at this point, I think we're questioning whether or not we are going to see it. Now, I can't tell you exactly why, but I can tell you we're monitoring it carefully and it's definitely not happening. At least in our business because we would see it in the Patient Assistance Program. On Botox migraines.

If you actually look at what is happening with patients on Botox migraines when the injectable CGRPS came into the market you did see a tick down in inpatients. But then Botox recovered, and it has roughly the same number of patients that it had back then it's slightly lower than it had back then. So what does CGRP ended up doing was expanding the market to some extent? And we're seeing a very similar phenomenon on the acute therapies as well. If you look at the scripts, the MBR access for the acute TGRPs, you can see that it's actually almost doubling every quarter the number of patients.

In the last quarter is about 90,000 to 100,000 MBR access. So I think these assets can significantly expand the market. I think two-thirds of our patients are patients that have switched on the acute have switched from trip downs to our agent, and one-third of them are naïve patients that we're bringing into the category. And again that's all about making it visible to patients who had this condition so that they go to their physician and ask for the therapy.

It's all about building markets essentially. And so, I think one of the things these assets will do is they will expand the market. Now I think as you expand the market obviously, Botox therapeutics some of those patients will ultimately -- if they don't get the relief that they're looking for an injectable CGRP or the acute therapy, they would eventually probably try injectable Botox. So we could see a little bit of growth there.

But the biggest part of the growth that we're going to see in this market is from Ubrelvy, and ultimately atogepant. It's a big market, and I think these agents will allow us to be able to significantly expand the market. I think this is clearly a multi-billion dollar market.

Liz Shea -- Vice President of Investor Relations

Thanks, Randall. Operator, next question, please.


Thank you. Our next question is from David Risinger from Morgan Stanley.

David Risinger -- Morgan Stanley -- Analyst

Thanks, very much. Excuse me. So I want to start with a high-level question Rick. Could you please discuss long-term immunology net pricing and formulary positioning prospects in the face of increasing competition in the coming years? And then second, just had a high-level question about cash flow.

I was hoping that you could discuss prospects for operating cash flow, capex, and free cash flow. Thank you very much.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Thanks, David. I'll take the first one. Rob will answer the second one for you. So if I look at long-term immunology which critically important is that you have the kinds of assets that allow that managed care organization or PBM to be able to cover the greatest number of patients.

This is a category where not every drug works on every patient that you have to have multiple options that are available on the formulary, and that's just -- that is the appropriate thing to do to make sure that patients have the drugs that they need to be able to be treated. I would say, we typically do very well with formulary access. That's driven primarily by the fact that our assets tend to be very attractive assets from their political profile. They establish significant market share positions and that's important for the Managed Care organization or the PBM.

So I don't see anything significantly impacting that going forward. I will -- I would assume we will maintain very high levels of formulary access. Net pricing. There's always some level of impact on pricing when you renegotiate contracts.

I don't anticipate that you will see a significant change going forward. So, I think it's more of the normal kind of competitive activity that we see in the marketplace.

Rob Michael -- Executive Vice President and Chief Financial Officer

And David this is Rob, I'll answer a question on cash flows. If you look at AbbVie and Allergan in 2019 on a combined basis generated about $19 billion almost $20 billion of operating cash flow. Capex runs close to a billion dollars and so, if you look at this year again, we have a partial year of Allergan trending toward a $16 billion operating cash flow number with all that less than a billion of capex. So you need to annualize that and then also consider the fact that we're going to generate earnings growth going forward.

But that should give you a good number to work with.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Thank you.

Liz Shea -- Vice President of Investor Relations

thanks, David. Operator, next question, please.


Thank you. Our next question is from Terence Flynn from Goldman Sachs.

Terence Flynn -- Goldman Sachs -- Analyst

Hi. Thanks for taking the questions. I was just wondering. First, maybe on the IBD front.

I know you have a number of readouts coming up for Rinvoq and Skyrizi here. Maybe you could just outline what current usage of targeted drugs in IBD is on a percentage basis, and how that compares to rheumatology and dermatology. And what you see as potential here to boost that uptake in IBD further. And then for your TNF, Steroid Conjugate Program.

What were the criteria that were key to lead to your choice of 154 as the go-forward asset? And then lastly on the Allergan integration, I know you said everything's on the track where it's going really well. You talked about some revenue synergy opportunities. Rick, I know you've laid out your expense synergy target of $2 billion in 2022. Maybe you could just talk about some of the puts and takes for 2021 as we think about the Allergan synergies on both sides.

Thank you.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Great on IBD usage. If you look at the penetration, I'd say IBD is an area where you have reasonable levels of biologic penetration because the disease particularly Crohn's disease is pretty severe. I think the challenge in IBD is that with the current therapies are available you still get suboptimal clinical efficacy for these patients and durability of that efficacy. And so -- and what physicians tend to do is they rotate patients through various treatments to try and to maintain them in control for a longer period of time.

So it is a market that is ripe for higher efficacy agents, and a market that is ripe for more agents to be available to allow for better treatment of those patients. And that's the key driver in that segment of what gets significant uptake. So when we see the data around IBD that will be important for us. Obviously, the early data looks good.

And ultimately, I think these assets along with Humira will continue -- will be able to provide the market with a significant new alternative. And I think that uptake will be good based on that.

Mike Severino -- Vice Chairman and President

This is Mike. I'll take the question about 154. So 3373 and 154 represent TNF steroid conjugate molecules that are in the clinic. They're very similar.

Similar to the extent that we view biology as being translatable between the two. But 154 includes some improvements in Linker Technology that relate to manufacturer ability, and ability to formulate at high concentration ease of formulation. And so those can be very important advantages for a successful molecule. We previously toplined the positive results from 3373.

We wanted to see that 154 gave us the PK performance and the exposure to achieve the pharmacademic coverage. We think we need it in the next stage of development. And as I said, we viewed biology as translatable between the two. So once we saw that PK performance and it matched your expectations and showed that 154 would give us the coverage that we were seeking at it at acceptable doses in the clinic.

We made the decision to advance that molecule into larger-scale trials.

Rob Michael -- Executive Vice President and Chief Financial Officer

Terence this is Rob. I'll take your question on synergy. So, we're not providing guidance for 2012 today I think a good way to think about the expense synergies is to run rate the 600 million partially synergies which would get to about a billion dollars. And then if you think about that ramp to greater than 2 billion by 2022, I think it's reasonable to a straight line that.

So if you think about what's going to drive the ramp that things like systems integration, leveraging procurement spend, will result in more synergies over time as well as network optimization. In the near term,  it's really driven more from me at redundancies like corporate infrastructure and R&D portfolio optimization. As relates to the revenue synergies, as we've now had a few months with the combined company we see opportunities as we think about investment in aesthetics where we've really amped up our DTC investment for Juvederm and Botox cosmetic. The ability to invest more in aesthetics similarly invest more in neuroscience whether that's real Botox therapeutic.

And then we look internationally, given the infrastructure we have the integrated brand team approach, we think there's opportunity to really leverage our market access capability. Our international affiliate structure to really drive that international growth for the company going forward for those Allergan brands as well.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Terence, the only thing I would add maybe to give you some perspective on the investment side. Allergan tended to what I would describe as host invest particularly DTC. But even in social media so they didn't -- and typically what we do with brands when we want to drive a maximum speed of market penetration is we invest at a steady-state and continue to do that for an extended period of time. So they might have invested heavily in one quarter and then gone dark in the next quarter, and then invested again and gone dark again.

We don't use that kind of a strategy. We tend to invest in the full year. And in our experience what that does is it gives you the fact that you have constant coverage gives you a maximum speed of penetration. And we clearly think that's going to be an advantage, particularly, in areas like aesthetics and neuroscience.

Liz Shea -- Vice President of Investor Relations

Thanks, Terence. Operator, next question, please. 


Thank you. Our next question is from Gregg Gilbert from Truist.

Gregg Gilbert -- Truist Securities -- Analyst

Thank you for getting me in. Good morning. Rick, It sounds like you think the neuroscience franchise might be one of the sleepers of the Allergan deal. And you've already framed the potential for Vraylar particularly if depression hits.

But I was curious if this development in neuroscience has taken on a new sense of urgency given the heft that you have now in that franchise, or whether you have enough going on there already. And then for Mike, I was hoping you could let us know when we'll see Phase 3 data for 951 in Parkinson's and give us a sneak preview of what you're looking for their profile wise. And lastly, can you frame for Botox therapeutic. Mike, what you've decided to pursue in terms of indications versus ones that you've taken off the table.

now that you've had some time to work with that. Thanks.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Thanks. I'd say on neuroscience the way to think about it is this is the way we're thinking about it. Is -- there's a significant opportunity drive Vraylar to be a very large product. I mean doubling or more depending upon the ability to get MDD.

And I'd also say in my migraines. When we get the full portfolio of migraine assets,  the migraine market is a big market. If you look at the acute market today it's probably about $1.5 billion. We believe it can grow to $4 billion, or $5 billion by 2025 with the right kinds of assets and the right kind of promotion.

And then if you look at the preventative market it's about $3 billion, and we believe that one in low, high-single to low-double digits with the right kinds of assets and the right kinds of promotion. So the first phase in neuroscience is nothing more than taking the assets we have now getting atogepant to the marketplace and then we have a whole portfolio of migraine products. And then maximizing the market share position of those assets in the market. That's phase one.

But I would say now that we have the infrastructure in place, Mike's BD team has been now starting to look at assets that would be complementary to that. And we did in the past because for a single antipsychotic, we wouldn't have wanted to build out the infrastructure. It just wouldn't have made sense for us. But now, we can basically add those kinds of assets to the infrastructure we have.

So it does give us another opportunity from a BD standpoint to be able to build the business longer term.

Mike Severino -- Vice Chairman and President

I'll take the second question and agree with everything Rick said. The other thing I'd add on BD and neuroscience is Nurse psychiatry is now clearly an area of strength for us and can be an area of interest and that can go beyond the antipsychotics as well. There are tremendous potential and unmet needs in areas like generalized anxiety disorder still in depression despite there are many agents on the market. Many, many patients remain inadequately treated.

So we would look broadly across that space. With respect to 951 in data timing, we'd expect to see results from our Phase 3 study in the second half of next year. And what we're looking for is really Duodopa efficacy because Duodopa is a transformational product. But it's also a product that is challenging to administer and nature of that product.

The fact that it requires the placement of a gastric tube that's been threaded into the small bowel and has to be maintained that limits the size of what's effectively the addressable market, not the market by the labeled indication but the proportion of patients within that population that would consider a therapy like that. In 951 has the potential to substantially expand that. It has an insulin pump like device subcutaneous delivery device. We think it'll broaden the number of patients within that labeled population who would consider such a therapy.

And this is really a very substantial market. So for example, if you look at Duodopa despite all these challenges it does about half a million dollars in sales if you look across similar therapies for advanced Parkinson's disease. The market is probably a billion and a half or more and that probably represents only a small part of the potential because much of it remains untapped. So we think that 951 can address that and we think that the profile that it will take to address that is Duodopa like efficacy with a more patient-friendly subcutaneous delivery device.

With respect to Botox indications. There are a number of indications both for Botox and for other toxins for novel toxins that we're considering in the therapeutic space. I think there's more work that we can do in the migraines space, although that has been an area of strength episodic migraines has patients that may benefit from a therapy like Botox. And there's still much more to do on the neurology side with respect to spasticity disorders that might be secondary to stroke or other conditions where there is still room to expand those indications.

When we look more broadly you know there are a number of potential interesting indications for neurotoxins. They might not be Botox, they may be novel toxins those could be things like prevention of a fib for example, and we're continuing to explore indications beyond that.

Liz Shea -- Vice President of Investor Relations

Thanks, Gregg. Operator, next question, please. 


Thank you. Our next question is from Tim Anderson from Wolfe Research.

Tim Anderson -- Wolfe Research -- Analyst

Thank you. High-level question for Rick. Despite Allergan being a very reasonable solution to the upcoming U.S. Humira  LOE in 2023 the multiple and AbbVie lower than it's ever been the entire drug group is out of favor.

Your multiple is about half of the peer group average. To me what that multiple says is that investors remain worried about what AbbVie looks like past 2023. So two questions related to this. The first is, why not give updated granular extended guidance that goes beyond 2023.

You've given long-term guidance in the past sometimes and that's resonated well with the market. So can we expect you might do this at some point soon? And the second question, why not go do more M&A in the near-term. We just saw Bristol do a $13 billion deal not far after closing Celgene and layering more product into your pipeline would help give investors assurances that there is life beyond 2023. And by virtue of how you answered an earlier question, you yourself basically said "there's not much new NMEs flow until 2025 and beyond.  Thank you.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Yes. I think if you look at Tim this is Rick. If you look at the PE and the whole sector obviously, the sector is under pressure from the point of environment and concerns about the political environment, and you are correct. We're at the lower end of that PE.

And I think that is driven by uncertainty about what the growth rate will be. On the other side of the LOE. What I would tell you is obviously, we have 10-year LLPs, so we know what we think that growth rate is on the other side of the LOE. And I can tell you that when I look at that growth rate it's robust.

Now, the market has to come around to that point of view. I'd say, we haven't always been right, but in total revenue, we've always been right. In fact, we've always been for the most part what our expectations were. And so we obviously, challenged it pretty hard.

And we have knowledge of what we believe the erosion curve will look like, we have knowledge of what we think our pipeline will deliver and what the additional indications will deliver. And look, I remember there was a tremendous amount of skepticism about when we gave you the $10 billion or $11 billion of risk-adjusted revenues for Rinvoq and Skyrizi back a year or two, something like that. There was a tremendous amount of skepticism and that's impossible. I don't hear very much of that now that these two assets of $2 billion and growing like rockets.

So I'd say our ability to assess what we can do with our assets is pretty high. Now that doesn't mean you shouldn't go out and get more things and we constantly look at where we find opportunities, we will clearly go pursue those after the opportunities that make sense and fit into our portfolio. You've seen us do transactions to continue to build the long-term future of our human business with Genmab and I-Mab and those two assets combined with what Venclexta and Imbruvica continue to do are going to give us a very robust long term performance in that franchise. I think in immunology, we're in pretty good shape between our internal pipeline both the additional indications on Skyrizi and Rinvoq.

And then what we have early on that we think will play out in a positive way. When we look at neuroscience, we just talked about that. We had the ability to be able to grow that certainly would invest heavily in aesthetics we have a tremendous amount of assets new toxins that we're working on and we're going to accelerate many of those new fillers and other kinds of opportunities that will build that aesthetics business to be able to grow rapidly. And so.

I feel pretty good about where we are.  I feel very good about where we are six months into the Allergan transaction. Certainly, Allergan has given us more growth as well. As we mentioned a moment ago when we look at Neuroscience. Neuroscience has clearly been, I think a nice positive upside for us and one that I think we can execute very well.

As far as guidance is concerned, I'm not saying we will never give guidance. But we want to give guidance when we're able to do it with a high degree of certainty because the last thing you want to do is provide a level of guidance that you don't have a high degree of certainty. And I know it's going to have some variability to it. You probably remember we did that on the international biosimilars, and we were off by not that much, but by some and the market didn't like the fact that we lost.

So you need to be awfully careful about how you provide that guidance in a way to make sure that you meet or exceed the guidelines. And at the point which we have that level of confidence, we may go out with longer-term guidance.

Liz Shea -- Vice President of Investor Relations

Thanks, Tim. The operator next -- we have time for one final question. 


Thank you. And our final question today is from Josh Schimmer from Evercore.

Josh Schimmer -- Evercore ISI -- Analyst

Last question. Thanks for squeezing me in. Just a couple of quick ones. Can you provide any color on this I receive a royalty oath? And can you comment on what you see as the incremental markets for the lower phase toxins and the new dermal filler and presbyopia if you view any of those as material? Thank you.

Mike Severino -- Vice Chairman and President

Hi, Josh. So on the Skyrizi royalty, keep in mind that we account for this as a business combination so it comes through can your considerations, so you don't see on a non-GAAP P&L. We don't disclose the royalty rates, but a good way to think about it is you know reasonable royalty you paid for a late-stage asset is a good way to think about what the royalty burden would be on a cash royalty burden will be on Skyrizi.

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

So I'd say the lower face toxins, and the lower phase fillers that we're working on probably the best way rather than trying to characterize individual indications, or toxins, or fillers are. We're trying to build a portfolio and a market activation strategy that will allow us to grow the Aesthetics business at a consistent double-digit rate. And it is both that internal pipeline and activating more patients and some IBD effort that will give us that. So certainly, those royalty phase toxins and fillers are designed to be able to support that growth going forward.

The Eye Care product until that product a minus product. I don't remember the specifics for you. But I'd call it a modest-sized product. Thank you.

Liz Shea -- Vice President of Investor Relations

Thanks, Josh. 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 signoff]

Duration: 89 minutes

Call participants:

Liz Shea -- Vice President of Investor Relations

Rick Gonzalez -- Chairman of the board and Chief Executive Officer

Mike Severino -- Vice Chairman and President

Rob Michael -- Executive Vice President and Chief Financial Officer

Chris Schott -- J.P. Morgan -- Analyst

Geoffrey Porges -- SVB Leerink -- Analyst

Vamil Divan -- Mizuho Securities -- Analyst

Steve Scala -- Cowen and Company -- Analyst

Naveen Jacob -- UBS -- Analyst

Randall Stanicky -- RBC Capital Markets -- Analyst

David Risinger -- Morgan Stanley -- Analyst

Terence Flynn -- Goldman Sachs -- Analyst

Gregg Gilbert -- Truist Securities -- Analyst

Tim Anderson -- Wolfe Research -- Analyst

Josh Schimmer -- Evercore ISI -- Analyst

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