Amgen - Q3 2023

Transcript

Operator (participant)

My name is Julianne, and I will be your conference facilitator today for Amgen's third quarter 2023 financial results conference call. All lines have been placed on mute to prevent any background noise. There will be a question and answer session at the conclusion of the last speaker's prepared remarks. In order to ensure that everyone has a chance to participate, we would like to request that you limit yourself to asking one question during the Q&A session. To ask a question, please press star followed by the number one on your telephone keypad. To withdraw your question, please press star one again. I would now like to introduce Justin Claeys, Vice President of Investor Relations. Mr. Claeys, you may now begin.

Justin Claeys (VP of Investor Relations)

Thank you, Julianne. Good morning, and welcome to our third quarter 2023 earnings call. Bob Bradway will lead the call and be followed by a broader review of our performance by Murdo Gordon, Vikram Karnani, who joined Amgen from Horizon Therapeutics following the October 6, 2023 acquisition close, David Reese and Peter Griffith. Given the timing of the Horizon Therapeutics acquisition close, our third quarter results do not include any contribution from Horizon. Vikram will provide select information from Horizon's third quarter product sales for future context. You should have received a link to our slides that we have posted. Through the course of our discussion today, we will make some forward-looking statements and use non-GAAP financial measures to describe our performance. Just a reminder that actual results can vary materially. I would now like to turn the call over to Robert.

Robert Bradway (Chairman and CEO)

Okay, thank you, Justin, and thank all of you for joining our call. It's an exciting time here at Amgen, and we're continuing to execute well this year, serving many more patients around the world with medicines such as Repatha, Evenity, and Tezspire, advancing a number of promising first-in-class medicines rapidly through our pipeline and preparing for our next wave of biosimilar launches. However, as this is our first earnings call following the close of our acquisition of Horizon Therapeutics, I thought we might turn our attention there first. The Horizon acquisition, coupled with our purchase of ChemoCentryx, which we acquired a little more than a year ago, gives Amgen a significant rare disease business that fits squarely within our overall strategy and will be additive to the growth we expect from our base business. At the heart of our strategy, of course, is innovation.

First or best-in-class medicines that make a big difference for patients suffering from serious diseases. The medicines in our rare disease portfolio, like TAVNEOS, TEPEZZA, KRYSTEXXA, and Uplizna, fit this description perfectly, and they'll benefit from Amgen's decades of experience in inflammatory diseases. These medicines are also early enough in their life cycles that we can positively impact their growth by leveraging Amgen's capabilities in process development, lifecycle management, and manufacturing. Finally, we've spent the past decade or so building out our international footprint with Amgen medicines now available in about 100 countries. And today, our rare disease sales come almost exclusively from the U.S., so we'll be able to leverage our global presence to quickly bring these medicines to patients around the world.

You'll hear more in a minute from Vikram Karnani, who joined us through the Horizon acquisition and is leading a newly created rare disease business, that is now, the fourth leg of Amgen's commercial stool, alongside our inflammation, oncology, and general medicine businesses. Turning to our financial performance in the quarter, total revenues were up 4% and earnings per share were up 6% compared with a year ago. Volume increased 11% globally, which represents our fourth consecutive quarter of double-digit volume growth, and we achieved good balance across all of our geographic regions and therapeutic areas. Seven of our medicines generated record sales in the quarter, and I'll highlight one of these, BLINCYTO, which delivered 55% sales growth in the third quarter.

We see continued upside potential for BLINCYTO as it is increasingly used in earlier lines of therapy and as practice guidelines are updated to reflect the role this medicine can play in treating a broad range of patients with acute lymphoblastic leukemia. Turning to our pipeline, we had the opportunity to discuss six potential first-in-class oncology assets with you recently following ESMO. Three of these have earned breakthrough therapy designations from the FDA, tarlatamab, BLINCYTO, and LUMAKRAS in combination with Vectibix in colorectal cancer. We also continue to progress trials for bemarituzumab in gastric cancer, for xaluritamig in prostate cancer, and for AMG 193, our PRMT5 inhibitor, which has generated responses across six solid tumors.

I'll just quickly note that AMG 193 was identified through our proprietary DNA-encoded library technology, which we added through the 2019 acquisition of Nuevolution, and it demonstrates our leadership in the emerging field of multispecific drugs that can address pathways that have long been recognized but considered inaccessible to traditional drug discovery efforts. In other pipeline news, we've completed enrollment in our Phase 2 obesity study for maridebart cafraglutide, which was formerly known as AMG 133. And finally, the FDA has accepted our BLA for a biosimilar to EYLEA. Looking at our business, we feel we have good momentum across the board. We feel we have everything we need with the portfolio, the pipeline, and the people to deliver attractive sales and earnings growth through the end of the decade and beyond.

As always, I want to thank Amgen employees around the world, including some 2,000 new colleagues focused on rare diseases, for their commitment to strong execution on behalf of the patients we serve. With that, I'll now turn over to Murdo Gordon. Murdo?

Murdo Gordon (EVP of Global Commercial Operations)

Thanks, Robert. I'm pleased with our performance in the third quarter. Execution is strong across the business, with record quarterly sales for seven brands and robust volume growth across our general medicine, inflammation, and hematology oncology portfolios. Product sales increased 5% year-over-year. Volume growth was 11%, with strength across our regions. US volume growth was 11%, and volume growth in our Europe, Latin America, Middle East, and Canada region was 8%. Consistent with our international expansion strategy, Asia Pacific continues to be our fastest-growing region, with 27% volume growth in the quarter. Starting with our general medicine business, which includes Repatha, Prolia, Evenity, and Aimovig. Overall revenue for these four products grew 21% year-over-year in the third quarter, driven by 20% volume growth.

Repatha sales increased 31% year-over-year in the third quarter, with volume growth of 44%, partially offset by lower net selling price. In the U.S., volume growth of 45% was driven by a record number of new patients starting treatment, more than doubling year-over-year. We saw declining net selling prices in the U.S., primarily driven by new formulary coverage by CVS in July for commercial patients. Outside the U.S., we saw 43% volume growth, with strength across our regions. There are still many more patients around the world who can benefit from Repatha, and we're rising to meet that challenge by investing and executing to drive awareness among physicians and patients. In the U.S., we have significantly expanded our primary care sales force and activated more than 15,000 new prescribers this year. We're also increasing promotion to patients through direct-to-consumer media efforts.

Transitioning to bone health, Prolia sales grew 14% year-over-year in the third quarter, primarily driven by 7% volume growth and higher net selling price. We expect volumes for Prolia to grow, supported by real-world evidence data presented earlier this year that demonstrate Prolia's superiority in reducing fracture risk when compared to alendronate in treatment-naive patients with postmenopausal osteoporosis. Evenity had record sales of $307 million for the quarter, driven by 48% volume growth. Osteoporosis disproportionately impacts postmenopausal women, and the diagnosis and treatment rates for these patients are low. In 2023, we expect approximately 3 million patients in the U.S. will be treated for postmenopausal osteoporosis. An estimated 40% of treated patients will be at very high risk of fracture, but only 6% of those high-risk patients will be treated with a bone-building product.

Evenity plays an important role in the bone builder market, with a 58% share in the U.S. and a 44% share in Japan. There's much more work to be done, and we'll continue to invest to ensure Evenity reaches the patients who need it. Otezla sales declined 10% year-over-year, driven by lower net selling price, unfavorable changes to estimated sales deductions, and lower inventory levels, partially offset by 1% volume growth in the US Otezla net price declines were driven by higher rebates to support and expand access for commercial and Medicare Part D patients. Our US Otezla business has been impacted by free drug programs associated with new treatment options that have entered the psoriasis marketplace.

We're beginning to see a reduced impact of these free drug programs as physicians and patients are experiencing barriers to access, given prior authorization requirements for these newer therapies. We have strong conviction in the growth potential of Otezla. With its unique indication for all severities of psoriasis, combined with an established clinical profile, broad payer coverage, a lack of testing required for initiation, and convenient oral administration. To realize that potential, we have increased our investment to ensure physicians and patients understand both the importance of treating psoriasis systemically and the safety and efficacy profile that Otezla offers. We're already seeing positive results from that increased investment, including significant growth in the number of patients requesting educational information and taking action on the Otezla website that generally indicate preparation for a discussion with a healthcare professional.

We've also recently increased our dermatology sales force by 20% to educate physicians about the benefits of Otezla for appropriate patients. With these increased investments, we expect to drive a return to growth for Otezla. Enbrel sales decreased 6% year-over-year, primarily driven by an 8% decline from unfavorable changes to estimated sales deductions. Year-over-year volume increased 1% in the third quarter, and the number of new patients in the U.S. starting treatment increased by 22%, driven by improved payer coverage and Enbrel's 20+ year track record of safety and efficacy. For the remainder of 2023, we expect our improved coverage will lead to continued growth in new patients and declining net selling price. Tezspire continues to show strong growth, with $161 million in sales in the third quarter.

Sales increased 21% sequentially, driven by 18% volume growth that benefited from the launch of our self-administered, pre-filled, single-use pen, which was approved by the US food and drug administration in the first quarter. We've now obtained coverage of the pen with the majority of pharmacy benefit managers, enabling easy access and convenient self-administration for patients in the U.S. with severe uncontrolled asthma. As we expected, Tezspire has both penetrated and helped grow the US asthma biologics market. In 2023, the number of new patients on asthma biologics has increased by over 20% year-over-year, and Tezspire's share of this expanded market is approximately 20%. Sales of TAVNEOS were $37 million in the quarter, with 26% quarter-over-quarter volume growth. In the U.S., approximately 2,300 patients have now been treated with TAVNEOS by over 1,500 healthcare professionals.

We continue to see an increase in awareness of TAVNEOS by rheumatologists and nephrologists, and exiting the quarter, we saw an increase in new patient start forms. Looking forward, we expect to bring TAVNEOS to even more patients with ANCA-associated vasculitis. AMGEVITA sales increased 30% year-over-year for the third quarter, driven by 53% volume growth, partially offset by lower net selling price. ex-US sales increased 10%, driven by 22% volume growth, partially offset by lower net selling price. Moving to our Hematology Oncology business, which includes LUMAKRAS, Kyprolis, XGEVA, Vectibix, Nplate, and BLINCYTO. Strong commercial execution and compelling new clinical data drove 15% volume growth year-over-year for these six innovative products. BLINCYTO sales grew 55% year-over-year to a record $220 million for the third quarter.

Volume growth of 56% was supported by broad prescribing to acute lymphoblastic leukemia patients, following positive data from the registration-enabling E1910 study presented late 2022, and updated NCCN guidelines that were issued in May. Long term, we see significant additional growth potential for BLINCYTO from earlier lines of therapy. LUMAKRAS reported $52 million in sales for the third quarter, a decline of 31% year-over-year. $22 million of this decline was driven by ongoing reimbursement negotiations in France. We see future growth opportunities for LUMAKRAS, driven by launches in new markets and our comprehensive global clinical development program. Vectibix sales increased 2% year-over-year for the third quarter to a record $252 million, driven by higher net selling price and 4% volume growth, partially offset by unfavorable foreign exchange impact.

Kyprolis grew 10% year-over-year, primarily driven by 8% volume growth, and Nplate sales increased 45% year-over-year for the third quarter, resulting from a $142 million order from the U.S. government. In the fourth quarter, we expect to fulfill an additional $62 million order for Nplate by the U.S. government. Given the strong performance of our Hematology Oncology products and the exciting new positive data presented at ESMO on our oncology pipeline, we look forward to helping more patients with their cancer therapy. Overall, our execution is strong across the business, driving growth and demonstrating our dedication to serving patients. And with the expansion of our rare disease portfolio, we're excited to serve many more patients around the world who can benefit from our therapies. And with that, I'll turn it over to Vikram.

Vikram Karnani (EVP and President of Global Commercial and Medical Affairs)

Thanks, Murdo. We're excited to bring together Horizon's medicines, pipeline, and rare disease expertise with Amgen's history of leadership in inflammatory diseases, global infrastructure, and world-class biologic capabilities. For those that are not as familiar with Horizon's portfolio, I will spend the next few minutes providing some background on our rare disease medicines. Horizon's business delivered $945 million of sales in the third quarter, representing 2% year-over-year sales growth with multiple positive leading indicators. Let me describe in more detail. TEPEZZA, the first and only medicine approved for the treatment of thyroid eye disease, regardless of disease activity or duration, generated $453 million of sales in the third quarter, representing 2% quarter-over-quarter growth.

We are confident that now, as we have officially joined forces and have onboarded the full commercial team, we will make significant progress in advancing this important product over time to patients. We are driving several initiatives to continue to build the U.S. thyroid eye disease market. In the third quarter, we saw a greater than 50% year-over-year increase in the number of TEPEZZA prescribers, supported by the April 2023 FDA label update to treat patients with thyroid eye disease, regardless of disease activity or duration. We are pleased with this progress and are continuing to educate the physician community on new clinical data and updated indication across the full spectrum of TED patients. Second, large national and regional payers are continuing to make favorable policy changes to help eligible patients access TEPEZZA.

To date, we have obtained favorable policy changes for greater than 30% of U.S.-covered lives, which are expected to take effect later this year and early next year. As a reminder, for Tepezza, there's a time lag between a patient being identified for Tepezza treatment and treatment being initiated. It can take up to 90 days for a patient enrollment form to move through the prior authorization process. Once that step is complete, then the patient's infusion needs to be scheduled at an appropriate site of care. This process takes time, and we have taken several important steps to minimize the time between patient identification and treatment initiation. Finally, we continue to see approximately 100,000 patients with moderate to severe disease in the U.S. that are appropriate for Tepezza, with the majority of these patients in low clinical activity score settings.

Therefore, the FDA's label update, combined with favorable medical policy changes by payers and supported by the expanding base of prescribing physicians, gives us a significant opportunity to reach more patients. These positive execution trends underpin our confidence in Tepezza's growth potential in the U.S. Moving on to markets outside the U.S., we continue to see international expansion as a meaningful long-term growth opportunity for Tepezza, which received its first ex-US approval in Brazil in the second quarter of this year. We are particularly excited about the opportunity to leverage Amgen's long-standing presence in multiple major ex-US markets, including Europe and in Japan, where we have reported positive data from the phase 3 OPTIC-J trial. We also continue to enroll a Tepezza phase III trial in Japanese patients with chronic or low clinical activity thyroid eye disease.

Krystexxa, the first and only medicine approved for uncontrolled gout, delivered a record $253 million of sales in the third quarter, representing 32% year-over-year growth. Sales are now annualizing at a $1 billion run rate. Performance in the third quarter reflected continued strong uptake in both the rheumatology and nephrology segments. Strong results were driven by execution across all phases of the patient journey: demand generation, stakeholder education, and adherence to treatment. The FDA approved Krystexxa's label change for combination with methotrexate in July 2022. We have seen a steady increase in uptake since then. Immunomodulation usage remained above 70% of new patient starts in the third quarter. We see an opportunity to redefine Krystexxa with methotrexate as a standard of care and reach even more of the over 100,000 uncontrolled gout patients in the U.S.

UPLIZNA sales increased 54% year-over-year in the third quarter to $67 million. International expansion is also underway, with UPLIZNA now launched in multiple ex-US markets, including Germany, France, Italy, Spain, and Brazil. Additional indications in development also support UPLIZNA's long-term growth potential, with phase 3 trials underway in both IgG4-related disease and myasthenia gravis. The rest of Horizon's portfolio generated $173 million of sales in the third quarter, primarily driven by our portfolio of ultra-rare medicines, RAVICTI, PROCYSBI, and ACTIMMUNE. We see an opportunity for this basket of products to continue to generate robust sales. Before I turn it over to David Reese, I want to take the opportunity to thank all my colleagues in the rare disease business for maintaining their focus on patients throughout a period of distraction over the last several months.

Looking ahead, we are excited to work together by leveraging Amgen and Horizon's combined capabilities to ensure our medicines reach more patients even faster, who are suffering from serious and rare diseases globally. I'll now turn it over to David.

David M. Reese (EVP of Research and Development)

Thank you, Vikram, and good morning, everyone. I'd like to begin by welcoming our new colleagues from Horizon. We are excited to be integrating Horizon's R&D capabilities with Amgen's to advance the promising Horizon pipeline. For R&D, the third quarter was one of high-quality execution as we progressed our innovative pipeline with important oncology data readouts, the addition of two breakthrough therapy designations, and completion of enrollment on key studies. We also advanced our innovative pipeline through rapid enrollment on multiple registration-enabling studies. Starting with general medicine, we have completed enrollment in the phase 2 study of maridebart cafraglutide in patients with obesity, with or without diabetes. The goal of this study is to generate data that will provide optionality to design a broad phase 3 program, leveraging the unique properties of maridebart cafraglutide that could potentially allow us to take a differentiated approach.

We anticipate top-line data from this 52-week study towards the end of 2024. The phase 3 outcome study of olpasiran, our potentially best-in-class Lp(a) targeting small interfering RNA molecule in atherosclerotic cardiovascular disease, is enrolling very well. In inflammation, beyond severe asthma, we are investigating additional indications with Tezspire, including separate phase 3 studies in chronic rhinosinusitis with nasal polyps, which is fully enrolled, and eosinophilic esophagitis. We also have a phase 2 study in COPD that has been fully enrolled, with top-line data anticipated in the first half of 2024. This study has recruited a broad population of COPD patients, including patients with both high and low eosinophil counts. Rocatinlimab, a first-in-class anti-OX40 monoclonal antibody being investigated in patients with moderate to severe atopic dermatitis, recruitment is off to a strong start on the ROCKET phase 3 clinical development program.

We have now randomized over 1,500 patients across the program. We are excited to present additional data from our expanded rheumatology portfolio following the acquisition of Horizon, including data from a phase 2 study of dazodalibep in Sjögren's syndrome, along with data from KRYSTEXXA, TAVNEOS, Otezla, and other molecules from our broad portfolio at the American College of Rheumatology Convergence 2023 meeting in November. I'll be brief with my remarks on our oncology portfolio, given the detailed oncology review last week. Based on the E1910 phase 3 study, the FDA has granted Blincyto Breakthrough Therapy Designation for the treatment of adult and pediatric patients with CD19-positive, Philadelphia chromosome negative, B-cell precursor, acute lymphoblastic leukemia during the consolidation phase of multiphase therapy. We see future growth of Blincyto from advancements into earlier lines of therapy and subcutaneous administration.

BLINCYTO also serves as a blueprint for how we plan to rapidly progress tarlatamab and Xaluritamig into earlier lines of therapy in settings of lower tumor burden. Along with experts in the field, we are very encouraged by tarlatamab, our BiTE molecule targeting DLL3. At ESMO, we presented data from DeLphi-301, a phase 2 study in late-stage small cell lung cancer, where we saw impressive response rates, durability of response, and overall survival in a setting where patients typically have limited options and a very poor prognosis. We are submitting these data to the FDA and are pleased that the FDA has granted tarlatamab Breakthrough Therapy Designation for the treatment of adult patients with extensive stage small cell lung cancer, with disease progression on or after platinum-based chemotherapy.

Given our confidence in these data, we are rapidly advancing tarlatamab into earlier lines of treatment, with multiple phase 3 studies underway or planned. Based on emerging clinical data, we are discontinuing PSMA-targeting bispecific AMG 340, and we'll focus our efforts on rapidly advancing xaluritamig in metastatic castration-resistant prostate cancer. We expect xaluritamig dose expansion cohorts to be fully enrolled by the end of the year and are planning to initiate additional studies in patients with earlier stage prostate cancer. With AMG 193, a small molecule MTA-cooperative PRMT5 inhibitor, we're encouraged by the responses we've seen across six MTAP-null solid tumors, the manageable safety profile, and preclinical evidence of CNS penetrance. We're now rapidly enrolling dose expansion cohorts. With that, I'll turn things over to Peter for the financial update.

Peter Griffith (CFO)

Thank you, David. I'll review our third quarter results before discussing our updated 2023 guidance. Turning to our third quarter financial results, which are shown on slide 44, total revenues of $6.9 billion grew 4% year-over-year, and non-GAAP earnings per share of $4.96 grew 6% year-over-year. The growth in revenues was due to product sales increasing 5% year-over-year, driven by 11% volume growth. Third quarter total non-GAAP operating expenses increased 4% year-over-year. We advanced our pipeline and invested in growth opportunities in the quarter while delivering a non-GAAP operating margin as a percent of product sales of 52%.

Non-GAAP cost of sales as a percent of product sales increased 1.3% points on a year-over-year basis to 17.4%, primarily driven by higher profit shares and changes in product mix. Non-GAAP R&D expenses in the quarter decreased 2% year-over-year due to lower spend in research and early pipeline activities, partially offset by higher spend in later-stage clinical programs and marketed products. Year-to-date, non-GAAP R&D expenses increased 5% due to higher spend in later-stage clinical programs and marketed products, partially offset by lower spend in research and early pipeline. Non-GAAP SG&A expenses in the third quarter increased 1% year-over-year. We continue to focus on prioritizing key investments, digitalization, driving productivity, and accelerating use cases for artificial intelligence. Non-GAAP OI&E were a net $225 million expense in the third quarter.

The year-over-year favorability was driven primarily by higher interest income and the change in Beijing accounting from equity method to mark-to-market investments, with the impact included only in our GAAP results. Our third quarter non-GAAP tax rate increased 3.2% points to 16.1%, primarily due to the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023. We continue to execute on our capital allocation priorities. First, we continue to prioritize investments in both internal and external innovation.... In the third quarter, we increased investments in programs, including maridebart, cafraglutide, I'll call it Mari from now on. Rocatinlimab, TAVNEOS, and ABP 206, our biosimilar to Opdivo. Second, we continue investing in our business for long-term growth, including through simultaneous construction of our state-of-the-art manufacturing facilities in Ohio and North Carolina.

We're excited for the anticipated licensure of our Ohio facility in the first half of 2024. Additionally, we're making investments in all parts of our business to leverage the power of generative AI opportunities. Third, we have a strong track record of returning capital to our shareholders and pay dividends of $2.13 per share in the third quarter, representing a 10% increase over the third quarter in 2022. The company generated $2.5 billion of free cash flow in the third quarter of 2023, compared with $2.8 billion in the third quarter of 2022. We will continue to generate strong cash flows. However, Q4 cash flow will be lower than historical patterns due to the timing of tax payments and Horizon transaction-related expenses. Turning to the outlook for the business for 2023 on slide 46.

We're pleased to have closed the acquisition of Horizon Therapeutics. We're updating off our full year 2023 guidance to include Horizon financial results starting October 6, 2023, so our Q4 results will exclude approximately one week of Horizon's results. We are raising our 2023 revenue guidance to $28.0 billion-$28.4 billion versus previous guidance of $26.6 billion-$27.4 billion. For 2023 non-GAAP earnings per share, we are narrowing the range to $18.20-$18.80 versus previous guidance of $17.80-$18.80. We will add Horizon's business into Q4 without material non-GAAP EPS dilution.

However, we do expect Q4 non-GAAP EPS to be lower than Q3 non-GAAP EPS because of planned investment increases in our business, including key assets in our innovative pipeline, beginning with MariTide, olpasiran, and AMG 193, and other strategic business investments, including generative AI use cases in all parts of our business. This sequential pattern is consistent with historical trends, and in addition, Q4 non-GAAP EPS will begin to include the recognition of interest expense related to the Horizon financing as a non-GAAP expense. Important additional points to consider as you model the remainder of 2023. We now expect other revenue for 2023 to be in the range of $1.2 billion-$1.3 billion, versus our prior range of $1.1 billion-$1.3 billion.

With the Horizon acquisition, we now anticipate full-year non-GAAP operating expense for 2023 to increase from our previous estimate of 3% to approximately 10% versus last year. Horizon represents approximately 5% points of this 10% year-over-year increase. We continue to expect the full-year 2023 operating margin as a percentage of product sales to be roughly 50%. We continue to expect non-GAAP cost of sales as a percentage of product sales to be between 16% and 17%. We now expect our non-GAAP R&D expenses to increase from our prior guidance of 5% to about 10% year-over-year. Horizon represents approximately 3% points of this 10% year-over-year increase. The additional 2% points are driven by planned increase in our investments in our innovative pipeline, including Mari, olpasiran, and AMG-193.

We continue to expect non-GAAP SG&A to be down year-over-year as a percentage of product sales, slightly. We now expect non-GAAP OI&E expenses to be in the range of $1.4 billion-$1.5 billion, up from our prior guidance of $1.1 billion-$1.2 billion. We expect Q4 OI&E to be about $700 million, reflecting interest expense related to the Horizon financing, which will be included in our non-GAAP results effective October sixth. And as you begin to model 2024, note that we expect 2024 OI&E to be consistent with this Q4 run rate. This higher interest expense is driven by the $28 billion of debt raised for the Horizon acquisition at a weighted average interest rate of 5.6%.

We expect to end 2023 with approximately $65 billion of long-term debt, including the current portion of it, and $11 billion of cash and cash equivalents. For the full year, we anticipate a non-GAAP tax rate of 16.5%-17%, down from prior guidance of 17.5%-18.5%. We expect approximately 540 million shares to be outstanding in Q4. This increase from Q3 is driven by the conversion of unvested Horizon equity awards into Amgen equity awards. Our 2023 capital expenditures are now projected to be approximately $950 million, up from our prior guidance of $925 million. The addition of Horizon's rare disease team further strengthens our confidence in delivering-... against our long-term growth objectives.

We continue to allocate capital to advance innovation at speed and at scale, and I'm incredibly grateful to our now 26,000+ colleagues for successfully executing our mission of serving patients. This concludes the financial update. Now I will ask our operator, Julianne, please open the lines for Q&A and remind our participants of the procedure to ask their question. Julianne?

Operator (participant)

Thank you. If you would like to ask a question, please press star, followed by one on your telephone keypad. If for any reason you would like to remove that question, please press star followed by one. Again, to ask a question, please press star one. Our first question comes from Michael Yee from Jefferies. Please go ahead. Your line is open.

Michael Yee (Managing Director in Healthcare Equity Research)

Hey, guys. Good morning. Thanks for all the details around the Horizon transaction. I just wanted to ask a question to David Reese. I mean, David, unless we're hiding under a rock, I guess obesity is, like, the biggest thing ever now, and wanted to understand your commentary and confidence around 133 and the profile around what you think that could be relative to leaders and how 786 would fit into that, given such a high bar for other orals. Thank you.

David M. Reese (EVP of Research and Development)

Yeah, sure. You know, as we've discussed before, Michael, in with 133, you know, we believe we have a potentially differentiated product based on the mechanism of action. It's a bifunctional, to remind everyone, that antagonizes GIPR based on genetic evidence, largely compiled by us, with two GLP-1 peptides stapled to the molecule for that mechanism of action. As I noted in the remarks, we've rapidly enrolled the phase 2 trial. There are multiple arms to this trial that explore three different doses, as well as different dosing intervals, that I think will give us broad optionality going forward.

You know, we were quite pleased with the phase 1 data in terms of depth of response, the kinetics of response, as well as persistence, and these are the things that we will be looking at in phase 2 as we go forward. So it's full steam ahead on this program, and we're looking forward to data from the phase 2 trial next year, which will really inform the breadth of the phase 3 trial that we're contemplating, which could be quite large. In terms of AMG 186 or 786, this is an orthogonal mechanism of action. We're bringing in data, and as we've indicated through the first half of next year or so, we anticipate presenting those data and determining the path forward.

As you note, you know, it's a high bar in this field, and we'd have to see the sort of profile that would, you know, give us the confidence to invest broadly in a molecule like that. I would also note we've got a suite of preclinical molecules, many of them non-incretin based in terms of mechanisms of action, that we'll be bringing forward over the next few years. So this is an area where we expect to be a long-term player. Thanks.

Operator (participant)

Thank you, Michael. Our next question comes from Yaron Werber, from Cowen. Please go ahead. Your line is open.

Yaron Werber (Managing Director and Senior Biotechnology Analyst)

Great, thanks for taking my question. Peter, just for you, the $700 million run rate, that was interest expense only, right? That's not including where you're recording sort of the Beijing contribution in the line right above it, in terms of other income. And then just secondly, again, on your guidance, you also mentioned 3%-10% increase year-over-year, and you mentioned 5%-10% going to R&D. The 3%-10% increase, what... Just remind us what that was, because SG&A is expected to be down, right, slightly over years. I just missed what that was.

Peter Griffith (CFO)

Right. Thank you, Yaron. The $700 is everything, so that's the full run rate. On your question on R&D, as I said in my remarks, you know, we've focused our spending on the later clinical and in-market portfolio that was slightly offset by some decreases in early research. But you know, we continue to spend and invest in the business, and we'll continue to do that. As you can see, we're fortunate to have a significant number of opportunities in phase 3 in the later stages, so that's what we'll stay focused on. We'll continue to differentially invest in the opportunities and innovation, and we're very excited about that.

Operator (participant)

Thank you, Yaron. Our next question comes from Terrence Flynn from Morgan Stanley. Please go ahead. Your line is open.

Terence Flynn (Managing Director and Senior U.S. Biopharma and Biotech Analyst)

Great, thanks for taking the question. Maybe a two-parter from me for Peter as well. Peter, again, I know you ran through a lot of numbers there at the end, but in terms of the revenue guidance raised for the year, can you just characterize if that was all coming from the Horizon portfolio, or if there was any other contribution from the underlying base business? And then the second part of the question is just any directional help with how to think about 2024 tax rate, as I know there's a number of moving pieces from, you know, some legislation, but then you obviously have the Horizon deal closed. So just directionally, can you help us out on 2024 tax rate? Thank you.

Peter Griffith (CFO)

Yeah. So, excuse me, on the tax rate, let me start with that. 2024 tax rate, we'll guide on that as we always do, at the beginning of the year. I would just say, I think you're thinking about the global minimum tax in pillar 2, and I would just note there's no consensus or predictability about how that whole OECD framework's gonna be implemented. I know different countries are doing different situations, you know-

... Rest assured, we look at everything and optimize our position as appropriate on something like that. So we'll give you guidance on that, next year at the beginning of the year. First part of the question?

Terence Flynn (Managing Director and Senior U.S. Biopharma and Biotech Analyst)

Revenue.

Peter Griffith (CFO)

Yeah, on revenue, look, we don't really break that down. I would just suggest that we continue to see strength in the business, and we continue to see our in-line portfolio perform very, very well. I would just note we had seven products with record sales in the quarter. We had Repatha up 31%, you know, in the quarter, year-over-year. And we've, you know, continued to see the hematology oncology portfolio was up 16%. So everything's, you know, strong in our base business. We're excited about that base business. It continues to perform really well, and we're very excited to have the rare disease business now. And looking forward to having that, as we said, is kind of the fourth stool of our commercial thrust forward.

We're seeing a good strength around the business in different areas, and we'll just continue to get more and more medicines to patients. I'd note the 11% volume growth is really important. Underneath that, 12% volume growth outside the United States, and underneath that, 27% volume growth in JAPAC, our fastest growing region. That's how we're looking at that. We're pleased with the momentum, and we're pleased to be able to raise the 28.0- 28.4.

Operator (participant)

Thank you, Terrence. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead. Your line is open.

Salveen Richter (Managing Director and Lead Analyst)

Good morning. Thanks for taking my question. With regard to the Horizon transaction, now that it's closed, could you just walk through the outlook for Tepezza and the other assets as we look to 2024 here? You talked about initiatives that you have to expand the patient population and ex-US being a growth lever. Just maybe walk us through that and when we might get updated long-term guidance, including Horizon. Thank you.

Robert Bradway (Chairman and CEO)

Yeah, maybe we'll take this in two parts, Salveen. It's Robert. Obviously, we're not gonna provide 2024 guidance here this morning, but we'll see whether we can give you a clear sense of the things that are exciting us when we look at those products for heading into to next year. And just generally, on the question of long-term guidance, as you've heard us say on a number of occasions, you know, we remain confident that we're on track to meet or beat the objectives that we established for 2030. But, you know, in some ways now, frankly, we're more focused on what we can deliver through 2031 and, you know, soon to be 2032 as well.

So, we reviewed in depth the oncology portfolio a couple of weeks ago, and that gave you a good sense for the moving pieces through the end of the decade. And, you know, we may seek to present a picture of the business in that way now, heading into next year so that you can, you know, get a more comprehensive, deep dive into the different segments of the business that are driving growth. But let's turn to your first question, which is the outlook for Horizon and the initiatives that are underway, in particular, with respect to Tepezza and Krystexxa and Uplizna. So, Vikram, why don't you fire away?

Vikram Karnani (EVP and President of Global Commercial and Medical Affairs)

Yep, thanks for the question. I think as I said in my prepared remarks, we have a lot of, lot of positive, leading indicators as we look at the business. I'll start with Tepezza. We're continuing to build that US TED market following the FDA's April 2023 label update, and that really helps us get the medicine to TED patients, regardless of disease activity or duration. What we've seen following that label update is that the payers are continuing to update their medical policies and make them more favorable so that more of these patients, more in the low CAS setting or the low clinical activity score setting, can now access Tepezza.

I think finally, from an execution standpoint, we see newer prescribers from both ophthalmologists as well as endocrinologists, increasing 50% year-over-year in this third quarter. So all of these indicators for Tepezza are positive, and we feel good about the execution of the team. And as I said, we have now combined forces with Amgen, and together, we should be able to drive the business in a positive way moving forward. I think talking about the story around Tepezza also is one of international growth. While we see a lot of positive trends in the U.S., we're pretty excited about what we can do as a combined company for patients outside the U.S. as well. We've talked about Brazil getting approval recently.

We've got chronic or OPTIC-J as our trial in Japan. We've talked about a chronic trial that's enrolling. Finally, we're getting ready for other markets, and we hope to bring the medicine to many more markets now as part of the combined company than we were talking about previously. So, TEPEZZA both signs very positive in the U.S. as well as globally. And as we've talked about the results for KRYSTEXXA and UPLIZNA, both those medicines perform really, really well. We have immunomodulation, with KRYSTEXXA being a major driver since the label update last year. That has continued to drive uptake since that time. We see that continuing into the future.

With UPLIZNA, it's the fastest-growing biologics in neuromyelitis optica spectrum disorders or NMOSD, and we see that momentum continue both in the U.S. as well as outside the U.S. So I think when I look at the overall portfolio, we have, we're operating from a position of strength, and now we can expand that even further with the combination with Amgen.

Robert Bradway (Chairman and CEO)

Thank you, Vikram.

Operator (participant)

Thank you. Thank you, Salveen. Our next question comes from Jay Olson from Oppenheimer. Please go ahead. Your line is open.

Jay Olson (Managing Director and Senior Analyst)

... Oh, hey, congrats on all the progress on so many fronts. Can you talk about your investments in AI technology and how that may influence your drug discovery and development over the next 5-10 years? Thank you.

Robert Bradway (Chairman and CEO)

Sure. I'll ask David Reese to address that, Jay.

David M. Reese (EVP of Research and Development)

Yeah, thanks, Jay. This is an area where we're very excited. You know, I like to characterize it as a hinge moment, where we're seeing the coming together or the unification of technology and biotechnology. I really think this is going to affect, over time, a qualitative change in how we do drug discovery and drug development. So everything from protein structure prediction, protein-protein interaction prediction at the molecular level to multi-omic analysis on extraordinarily large data sets, which is only tractable through AI or machine learning, dense clinical trials data, and then real-world evidence and real-world data. When you look across that spectrum, I believe we probably have the largest data sets in the industry.

And so we're putting the tools in place and the foundational models to really mine those data for deeper insights into biology and then all the way out into the market. We'll talk about this more over time, but this is going to be an area of investment, and it can be overhyped. It's not a panacea, but it is absolutely going to be the most powerful tool we have seen in a long, long time.

Operator (participant)

Thank you, Jay. Our next question comes from Umar Rafiq from Evercore ISI. Please go ahead. Your line is open.

Umar Raffat (VP and Equity Research Analyst)

Hi, guys. Thanks for taking my question. David, I have a two-part question on AMG 786, the oral for obesity. First, I noticed you guys dropped a cohort in your SAD portion of the trial. Is that because you ran into MTD? And then also, I noticed the exclusion criteria around suicide ideation were intensified, and I can't tell if we could be reading into that or not. Would love to get any color. Thank you.

David M. Reese (EVP of Research and Development)

Yeah, thanks, Umar. On the latter, I wouldn't overthink that at all. I don't think there's anything there. You know, in terms of, you know, the dosing that we do, you know, this is always adjusted as we move through phase 1 trials. As I indicated, you know, we're bringing in the data now. We're taking a look at that, you know, and the constellation of clinical data, updated preclinical data, and I think we'll have that all together as we go into next year, and that will determine the potential path forward for AMG 786. And just to remind everyone, this is a target that is not an incretin-based target.

Operator (participant)

Thank you, Umar. Our next question comes from Robyn Karnauskas from Truist Securities. Please go ahead. Your line is open.

Robyn Karnauskas (Managing Director and Senior Biotech Analyst)

Hi, thanks for taking my question. I do have a follow-up to Salveen's question, actually. So Tepezza has not, you know, gotten a lot of market share. There's so much room to grow in the TED space. Can you walk me through, like, how Amgen can actually help grow that business? Because I'm confused by whether it's the hearing loss or reimbursement or what are really the levers that will actually grow that company, grow that business. Tepezza, sorry, Tepezza. But I think that there's a lot of room to grow, and given your strength, you could probably make that work. So how do you intend to do that?

Robert Bradway (Chairman and CEO)

Okay, thank you, Robyn. So I think it's a two-part question there on Tepezza. We may tackle it in two parts, the combination of Vikram and Murdo. So go ahead, Vikram, why don't you start?

Vikram Karnani (EVP and President of Global Commercial and Medical Affairs)

Yeah, thanks for the question. As I said earlier, I think one of the areas that has something that happened this year was the FDA update. Now, when the label updates to patients that are treated regardless of disease activity or duration, many of these patients, in fact, I would say more of these patients are being treated by prescribers such as endocrinologists and ophthalmologists. And that's what the team has been focused on working through, you know, making sure there are educational programs available to these physicians, so that we can widen our prescriber base from the original set of prescribers that started treating patients at launch. So it's really important to understand that expanding the prescriber base is a critical driver for that success going forward.

As we've seen, new prescribers have increased 50% year-over-year. As we continue to work through these new low CAS or low clinical activity patients, we also have to remember that when they are prescribed the medicine, payers need to open up access to the medicine. Our market access team has been working pretty diligently to make sure that payers continue to update their medical policies. What we have seen is more than 30% of U.S.-covered lives are now eligible for patients that can access Tepezza with more open or more favorable policies. This has to continue, and both of these are areas that we will continue to work on as we go into early next year and beyond.

Maybe I'll turn it over to Murdo to add his comments as well.

Murdo Gordon (EVP of Global Commercial Operations)

Yeah, thanks, Vikram. Hi, Robyn. I would add much the same way when we acquired ChemoCentryx and TAVNEOS, we realized that there was a low level of awareness of TAVNEOS. Now, what we did there was we added reminder messaging to some of our broader rheumatology covered sales forces to increase awareness of the data associated with TAVNEOS and ANCA-associated vasculitis patients. We've seen a corresponding increase in utilization, of course, driven by awareness of that product. So the core team is still promoting the attributes of the product and educating physicians, but there's a broader group of field personnel building general awareness of that product.

What I think, Vikram and I are talking about is, the Amgen teams that cover endocrinologists, who are involved in the diagnosing and treatment of thyroid eye disease, would be an ideal opportunity for us to broaden awareness among that community of endocrinologists who are diagnosing and treating thyroid eye disease today to augment the great work that is happening with the rare disease teams under Vikram's leadership. So there's a number of things like that, where we can scale and speed up the building of awareness, for example, of the new data that Vikram was just describing and the broadening of the label language. Vikram also mentioned the international expansion. The original plan was quite ambitious for Horizon.

We've actually increased the number of markets that we intend to file and launch in, in a shorter period of time. That would be an additional opportunity for growth, given the strength of the two companies now combined.

Robert Bradway (Chairman and CEO)

I might just add also, Robyn, that in terms of the time course of events here, I think now that we reflect back on a year of ownership of ChemoCentryx, we can really start to see the benefit of what Murdo just described, kicking in in the last few weeks and months. So, it takes a little bit of while, but I think our confidence is that, you know, over that period of time, you know, we've been able to find the ways that we can add distinctive value to that product. And, you know, we're hoping a similar thing will happen with respect to the new rare disease molecules that we brought on board.

So it's not like walk in, flip a light switch, and suddenly things are performing on a different track, but rather, you come in, work together, identify the ways in which we can be additive in the marketplace. I'm hopeful that we'll see during the course of 2024, the momentum build for the combined organization on these products.

Operator (participant)

Thank you, Robyn. Our next question comes from David Risinger from Leerink Partners. Please go ahead. Your line is open.

David Risinger (Senior Managing Director and Senior Research Analyst)

Yes, thanks very much. So my question is on oral obesity development. Regarding phase one candidate, 786, management has consistently emphasized that it also has a suite of oral preclinical products, and so should we take away that we should be viewing 786 as more of a wild card rather than something that Amgen has conviction in at this point? And when do you expect to be able to start phase one for another oral preclinical candidate? Might that happen in 2024 or not until 2025? And then separately, just to... I wanted to squeeze in a quick financial question. Do you expect Horizon product channel inventory work down in the fourth quarter to significantly constrain reported net Horizon sales in the fourth quarter? Thank you.

David M. Reese (EVP of Research and Development)

Yeah. Thanks, David. David Reese, I'll start and then turn things over to Murdo and Vikram. You know, in terms of oral obesity molecule, 786, as I, as I, you know, I've said, it, it has a novel mechanism of action. It's a phase one molecule, so you should view it as a phase one molecule, and, and we're, you know, bringing in, as the data I said, and we'll take a look at that, as we get into the new year, and make a determination on a potential path forward for that molecule. I, I, I wouldn't view it as anything more or less than a, than a phase 1 asset with a novel mechanism of action.

You know, in terms of additional molecules and when we might file INDs and launch first in human trials, you know, we'll give guidance as that portfolio advances over time. Again, many of those molecules are targets that we emanated from deCODE Genetics, our colleagues in Iceland. And I'll provide, you know, further information as we get ready to move towards the clinic, but this is playing the long game. If you step back, you know, look, this field is in its infancy. We are just beginning to understand the complex metabolic arrangements that occur with obesity, and there are clearly different forms of obesity.

There's a lot of work to do, and as I've indicated, our intent here is to play the long game, given that this is one of the major public health challenges of the 21st century. So let me now hand it over to Vikram and Murdo for additional commentary on your second question.

Murdo Gordon (EVP of Global Commercial Operations)

Yeah, David, I just want to make sure that I heard your question right. It was about inventory and product wind down. Look, I don't think we're going to comment on that specific aspect. I think our team remains focused on driving demand and working with physicians to educate them and expanding the use of Otezla for appropriate patients. And that's where we're really focused, as our primary driver of net sales growth.

Operator (participant)

Thank you, David. Our next question comes from Chris Raymond from Piper Sandler. Please go ahead. Your line is open.

Chris Raymond (Managing Director and Senior Biotechnology Analyst)

Hey, thanks for taking the question. I just maybe a commercial question on your dermatology strategy, and specifically on Otezla, just on the dynamic that you guys talked about with, you know, free competitor drug. Presumably, that's the Sotyktu scenario. And I think I heard you guys, you know, you've been calling this issue out for some time, you know, it but also with the investment that you're making in the dermatology sales force, I think I heard you say today that you're increasing that sales force sort of 20% or so. Is the implication that once the competitor free drug program runs its course, that Otezla volume should increase? Or what's your sense of what happens to volume?

Maybe I'll ask it another way: If that volume increase doesn't materialize, do you need additional derm portfolio offerings to support that added effort? Thanks.

Murdo Gordon (EVP of Global Commercial Operations)

Thanks for the question, Chris. It's Murdo. So, let's just recapitulate what's happening in this market. At the beginning of the year, you had a number of new launches, not just SoTyktu, with novel topicals coming into the market, as well as a novel oral. And, every one of those products had very generous free drug programs, and that had two effects on Otezla. There were topical patients who would have normally moved to their first systemic option, who tried the new topical treatments on a free drug basis. And at the same time, there was a launch of a new oral that had a very generous free drug program.

So Otezla, which sources the majority of its growth from topical patients, first systemic, in other words, biologic-naive patients, Otezla got squeezed in the first and second quarter on the basis of those new programs coming into the market. What we've seen since those two events in the market is that the novel topicals have flattened out in their growth and have pulled back to some extent on their free drug offering. The other oral therapy, SoTyktu, continues to provide free drug, and so continues to have some effect on Otezla. What we think will happen, and we're already seeing the very early signals of this, is that we will continue to source our new growth from the topical patients, bio-naive patients, given that Otezla is the ideal for a systemic agent.

We have established ourselves with really strong access in the market, so we don't need to provide free drug programs to the extent that everybody else is. And then, as the contracting cycle for 2024 matures, and we see what the actual access is for some of the other competitors in the market, including the new oral, we should be able to give better guidance on our growth prospects for the future. But we almost certainly expect the impact of the free goods program to continue to reduce, and that will help us grow Otezla. The investments we made are really just kicking in this quarter, so the expansion in the field force, and your number was right, by 20%. The derm team was just deployed at the beginning of Q4, so they are only in field as of a few weeks.

So that impact is not in the historical performance of the brand. And our direct-to-consumer spend has been increased for the fourth quarter as well. So we'll be able to tell you more as we go forward, but we feel, given the very large number of patients here who continue to persist on topicals when they really are better candidates for a systemic agent, will convert to Otezla as we build into that market. And just a reminder, we're the only product in the market that has a broad label, regardless of severity of psoriasis. So we're optimistic and we're enthusiastic, and that's why we've made these investments, and we'll continue to look to add to our dermatology portfolio as we go forward.

Operator (participant)

Chris, our next question comes from Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.

Mohit Bansal (Managing Director and Co-Head of Therapeutics Research)

Great. Thank you very much for taking my question, and thank you for changing the time to make sure people can enjoy Halloween. So maybe one question on sequential growth. If I look at second quarter from third quarter, it seems like pretty much every product, even including and accounts for the government budget, seems to be down. I know that you warned about this in the second quarter call, regarding Medicare donut hole, but can you talk a little bit about the dynamics there, and how should we be thinking about this going forward?

Murdo Gordon (EVP of Global Commercial Operations)

Yeah, Mohit, I don't think every product's down. I think we had a number of products posting pretty significant double-digit growth in the quarter, and those are products that we continue to expect long-term growth from. Products like Repatha, Evenity, Prolia, our hemonc portfolio, Blincyto in particular. So you know, we're seeing some strength in our priority growth brands that we expect to continue to drive. What we did have in the quarter were a number of adjustments from prior period on net sales. So there was one particular adjustment on Lumakras, which was based on a year-over-year change in the negotiations we have on reimbursement. So in France, for example, we have an early temporary access program, an ATU program.

Since 2021, Lumakras has been available in France, and we took a $22 million accrual in the quarter for those sales on the basis of price negotiations we're having in France. We had a number of events like that related to price in the quarter, and as you mentioned, we are entering the donut hole for some of our products. Overall, I think unit volume growth, very strong, a few price effects, on select products in the portfolio, and a little bit of donut hole impact.

Operator (participant)

Thank you, Mohit. Our next question comes from Gregory Renza, from RBC Capital Markets. Please go ahead. Your line is open.

Gregory Renza (Director and Senior Biotechnology Research Analyst)

... Great. Good morning, Robert and team, and congrats on the progress, and thanks for taking my question. Robert, just circling back to the obesity market again, and as you and the team focus on really being best, being first or and/or best in class across markets, I'm just curious how you and the team view and anticipate how different the obesity market could look, and how you see the unmet need morphing by the time a program from Amgen is ready for prime time. But would there be a need to look not just internally but externally to accelerate those efforts, especially if things are evolving so quickly? Thanks again, and congrats on the progress.

Robert Bradway (Chairman and CEO)

We're very excited about what we see so far emerging from our early work in obesity. I think over time, you got the sense of this from David Reese. This is likely to be a heterogeneous disease. There are probably gonna be a number of different ways to have to go at it. But what encourages us right now is what we think of as an emerging differentiated profile for our approach versus the competition. And maybe, Murdo, you want to just jump in and remind Gregory about the basis of differentiation that we see so far in our data from the competition and why we think that gives us a good foothold for entering the market.

Murdo Gordon (EVP of Global Commercial Operations)

Yeah. Thanks, Robert. I like the way the question was framed. It sometimes gets framed as, you know, what are you gonna do when with these entrenched products in the market? And I'd just like to remind people how young this market is and how much more is left to unfold. What we're seeing in the early days is we're seeing a lot of patients trying these products, losing weight, but then not persisting with their treatment and regaining weight. So we think that there's an opportunity in the market long term for a product that can bring about very strong weight loss, both rapid and sustained over time, with convenient dosing.

And I think that that's where, AMG 133 or MariTide, maridebart cafraglutide really has an opportunity to differentiate itself from what is available in the market today. We've seen the durability of, that product between doses, and we think based on the phase 2 and the number of different dosing cohorts we have being explored in that trial, we'll be able to, find the right balance of efficacy and the ability, based on convenient dosing, to sustain that weight loss over time. And of course, the goal here is not just to lose weight, but to improve a number of sequelae or outcomes from, people who carry extra weight over the course of their life.

And that's what we're starting to see with others reading out in event-driven trials, and we'll see more data as the medical congresses pass by in these next few months. But our hope is to bring about real improvement in outcomes with a highly efficacious and highly convenient product like 133.

Operator (participant)

Thank you, Gregory. Our next question comes from Geoff Meacham from Bank of America. Please go ahead. Your line is open.

Geoff Meacham (Managing Director and Research Analyst)

Morning, guys. Thanks so much for the question. Murdo, you know, it's been a long time coming for Repatha infusion. Are you guys finally hitting a commercial tipping point with payers, or do you think there is an increasing interest among cardiologists? I guess I wasn't sure how, you know, the current market is, and looking forward, how about the impact? How do you guys see it from a couple of the ongoing phase 3s and 4s? Thank you.

Murdo Gordon (EVP of Global Commercial Operations)

Thanks for the question, Geoff. Yes, it's been a bit of a journey, and the COVID pandemic didn't help us in our efforts to educate and convince cardiologists that they needed to do more to be more aggressive in treating their patients' LDL cholesterol. I do think we've reached a tipping point in cardiology, and I do think we've reached a tipping point with payers. We now have over 90% commercial lives covered. We anticipate being able to continue to progress our Medicare Part D coverage, and we're seeing, you know, the PCSK9 category, driven primarily by our 80% share of that category, really starting to move now. Our new patient volume growth is good, not just in the U.S., but around the world.

We are now seeing more and more primary care physicians using PCSK9s in combination with other drugs to more aggressively lower LDL in high-risk ASCVD patients. So the phases are pretty clear. Payer coverage established, affordability for patients established, cardiologists now prescribing with frequency, and now moving into primary care. And we'll be adding direct-to-consumer campaign investment to that mix. So yeah, I think we've reached a tipping point on Repatha, Geoff, and I'm bullish on what we can do to further expand that product both from a volume and net sales perspective.

Operator (participant)

Thank you, Geoff. Our next question comes from Chris Schott from J.P. Morgan. Please go ahead. Your line is open.

Chris Schott (Managing Director and Senior Equity Research Analyst)

Great. Thanks so much for the question. Just a question on longer-term margins. So I guess Post-Horizon, and I guess with the ramp of your pipeline, including some potentially very large obesity studies over time, I guess, just directionally, how should we be thinking about margins from here? I guess, is this kind of 50% or slightly above 50% range, a reasonable target for the company, or just any considerations we should keep in mind as we kind of balance, I guess, Horizon versus investment? Thank you.

Robert Bradway (Chairman and CEO)

So, we're not going to give updated margin guidance on this call, Chris, but I think we've been pretty clear about what the trail should look like. We're focused on remaining leading efficient player in our industry. We've been able to achieve leading operating margins over time. There's nothing that we see in the Horizon Business specifically that would lead us to conclude differently from that. So, you know, we expect that at a full run rate, capitalizing on our in-place infrastructure internationally and manufacturing and process development, that the margins of that business will be attractive in our hands.

You know, the reference that Peter made to R&D spend earlier, obviously, to the extent that we get into a number of phase III trials in the middle years here of the decade for Lp and for obesity products, you know, that may have an effect on overall margins, but we'll have plenty of time to talk about that in advance so that nobody's surprised if the margins start moving around. So again, we've demonstrated a, you know, pretty consistent ability to manage the cost structure of the business, and, you know, that's, that's something that we're determined to maintain.

Operator (participant)

Thank you, Chris. Our next question comes from Evan Segerman from BMO. Please go ahead. Your line is open.

Evan Segerman (Managing Director and Senior Research Analyst)

Hi, guys. Thank you so much for the call on this call today. So the growth in KRYSTEXXA is pretty impressive. Just wondering how the mentioned $1 billion run rate compares with your expectations going into the deal? And then taking a step back, we saw a JAMA article about the use of type two diabetes meds for gout. How are you seeing this in the broader gout space? Is this something we should be concerned about when it comes to KRYSTEXXA? Thank you.

Robert Bradway (Chairman and CEO)

Maybe we'll take this in two parts. First, with respect to KRYSTEXXA, you know, I'd say KRYSTEXXA is performing very well, and we believed it would. Again, we think there's a tremendously large unmet medical need here and that KRYSTEXXA with methotrexate is serving the marketplace well, so we're looking forward to working with our colleagues on it. And overall, I'd say that the business is proceeding as we thought it would to this point. The things that we thought were important to have in hand, like the chronic indication for TEPEZZA, like international datasets that were made available with the OPTIC-J trial, like the progress we've made in Brazil, you know, et cetera. Those were things that we wanted to have in hand and now do.

And again, Uplizna is also performing very much in line as we expected it would. So, we see three growth opportunities there, and, we see ways for the Amgen-based business to add value to what Vikram will be running now in our rare business area. And then with respect to the question on diabetes, unless David-

David M. Reese (EVP of Research and Development)

Yeah, I mean, I think the broader context here is important. You know, these patients have, you know, severe, uncontrolled gout. They are often facing amputations, for example, because of the severity of the disease. And so, you know, there are a large number of these patients that are currently not being served in the market, in clinical practice, and so our focus is on reaching those patients, where the quality of life impediments are quite significant and the effects of the drug can be quite dramatic in improving the disease course and improving that sort of quality of life. So that's the focus right now. I wouldn't get distracted by some of the other potential associations.

Robert Bradway (Chairman and CEO)

Operator, I think we have two more calls in the log here, so why don't we take two more, and then we'll thank our colleagues and let them get on with the day?

Operator (participant)

Certainly. Thank you, Evan. Our next question comes from Tim Anderson from Wolfe Research. Please go ahead. Your line is open.

Tim Anderson (Managing Director and Senior Equity Research Analyst)

Thank you. On AMG 133, maybe this is a silly question, but is it at all possible that you can start phase III in 2024? The main way to do this would be to do an early or interim look of sorts at the phase II trial before the primary completion date. I know you're guiding for top line on that in late 2024. Thank you.

David M. Reese (EVP of Research and Development)

Yeah, I mean, as we go through 2024, we'll give guidance on when we expect the, you know, the phase 3 program to launch. You know, as is customary in these programs, we will take an interim look. That will remain blinded. We will not release that externally because this is a 52-week study, but that will help at least guide our thinking. Also recall that the FDA requires a certain safety database before you launch phase III trials here, and so as we get into next year and start to have those conversations, we'll be able to give more definitive guidance as to when you can expect the launch of the phase 3 program and what that suite of studies might look like.

Robert Bradway (Chairman and CEO)

Let's take our last question.

Operator (participant)

Thank you, Tim. Thank you, Tim. Our last question will come from Colin Bristow from UBS. Please go ahead. Your line is open.

Colin Bristow (Managing Director and Biotechnology Analyst)

Good morning, and thanks for taking the questions. Maybe just a quick follow-up on 133. Just as we think about this from a commercial perspective, this is obviously an antibody backbone. It's going to be an injectable. Just in light of margin that's achievable with this, just help us think through that. Thanks.

Murdo Gordon (EVP of Global Commercial Operations)

Well, Colin, you rightly point out that, you know, this is an antibody backbone. The properties of that, obviously, as I was alluding to earlier, could be that you can dose it much less frequently than you have to with the current therapies on the market. We also think, given the potential differentiation on efficacy and possibly tolerability, that we'll be able to establish a very strong position in the market for people who need rapid, deep, and sustained weight loss that they can manage over time so that they can gain the benefits, the reduction in cardiovascular risk, the improvement in outcomes from that treatment.

But we expect, as David said, to develop this product across a suite of Phase III experiments, and we expect to be able to take a decent share of the market, which will drive a good return on our investment in that product.

Operator (participant)

Thank you, Colin. I would now like to turn the call back over to Robert Bradway for closing remarks.

Robert Bradway (Chairman and CEO)

Okay. Well, let me thank all of you for joining us this morning, and, we hope that the choice of doing this in the morning frees you up to go enjoy the afternoon and evening of, trick-or-treating wherever you are. But we, again, appreciate your support. It's been an eventful few months at Amgen, and we'll look forward to having an opportunity to regather with you and report on the fourth quarter when we get to the new year. Many thanks.

Operator (participant)

This concludes our 2023 Q3 earnings call. You may now disconnect.