David M. Reese
Executive Vice President, Research and Development at Amgen
Thanks, Murdo. Good afternoon, everyone. For research and development, last year was one of high-quality execution and on-time delivery of results as we continue to progress our innovative pipeline. In general medicine, we strengthened our cardiovascular franchise and emerging portfolio of obesity assets. Two areas of significant unmet need affecting millions of patients globally. The path of course is the cornerstone of these efforts and last November at AHA, we presented FOURIER-open label extension data. These data were recognized by the American College of Cardiology expert consensus decision pathway, which indicated there appears to be no LDL-cholesterol level below which benefits thesis. Additionally, LDL-cholesterol recommendations were updated to reflect a reduction in target LDL levels and highest risk patients from 70 milligrams to 55 milligrams per deciliter. This is a level that is not attainable for a large number of patients without PCSK9 inhibitor therapy.
Another molecule that we're excited about is Olpasiran. At AHA, we presented Phase 2 data, where Olpasiran dose 75 milligrams or higher every 12 weeks, reduced Lp(a) concentrations by 95% to 100% in patients with established atherosclerotic cardiovascular disease, with baseline Lp(a) levels of approximately 260 nanomoles per liter. I'll pass around appeared both safe and well-tolerated in this study. We are encouraged by these data, particularly our dosing frequency, safety and tolerability profile and degree of Lp(a) reduction. We have initiated a Phase 3 outcome study in 6,000 subjects with atherosclerotic cardiovascular disease and significantly elevated Lp(a) levels of at least 200 nanomoles per liter.
Now turning to obesity. In December, we presented data from a Phase 1 study where AMG 133 appeared safe, well-tolerated and demonstrated a 14.5% reduction in body weight at day 85, following three monthly subcutaneous injections. Party weight reductions were observed up to a 150 days after the final AMG 133 administration. Given these favorable attributes, we are now enrolling a 570 subject Phase 2 study to explore AMG 133 in patients with obesity with or without diabetes and related comorbidities. The study will also investigate different dosing levels and regimens [Technical Issues] 4%. Recall, our Q4 2021 results included approximately $200 million of favorable impact to other income and expense resulting from a gain on our BeiGene investment. Full year non-GAAP EPS of $17.69 grew 27% versus our recast 2021 results. Non-GAAP Q4 operating expenses were unchanged year-over-year, while full year non-GAAP operating expenses declined 12%. The full year include the impacts in 2021 of the $1.5 billion Five Prime IP, R&D charge and the $400 million licensing payment to KKC for Rocatinlimab.
We advanced our pipeline and invested in-product launch activities in 2022, while delivering a 51% non-GAAP operating margin as a percentage of product sales. On a non-GAAP basis, Q4 cost of sales as a percent of product sales decreased 1.2 percentage points on a year-over-year basis, down to 16.3%. For the full year, cost of sales as a percentage of product sales decreased by 0.5 percentage points, down to 15.9%. Both the quarter and full year improvements were primarily due to fewer COVID-19 antibody shipments and lower manufacturing costs, partially offset by changes in our product mix.
Non-GAAP R&D spend in the fourth quarter decreased 2% year-over-year, primarily due to higher business development activity in 2021, including our upfront payments in connection with our generate Bio-Medicines and Arrakis therapeutics collaborations, along with lower marketed product support. This was partially offset by higher support for key assets in early and late stage programs. However, adjusted for 2021 BD activity, Q4 2022 R&D investment increased 7% year-over-year, and for the full year, non-GAAP R&D spend declined 8% based on the same drivers at the fourth quarter, however adjusted for BD activity, full year 2022 R&D investment increased by 5%.
Q4 non-GAAP SG&A expenses increased 2% year-over-year, driven by higher marketed product support, including investments in our priority products, TEZSPIRE, EVENITY and Repatha. For the full year SG&A expenses were unchanged year-over-year as increased investments for all priority brands were offset by productivity gains, continuous improvement and reallocation from mature brands. Non-GAAP other income and expenses were about $470 million in expense in the fourth quarter, a $250 million increase year-over-year, primarily driven by the previously mentioned gains in 2021, that we've recognized from our investment in BeiGene. For the full year non-GAAP other income and expenses were approximately $1.7 billion.
So now, turning to the outlook for the business for 2023. Our outlook is Amgen-only on a stand-alone basis without any adjustments for the announced Horizon acquisition. It's important to remember that currently, at current publicly available consensus estimates are derived from a combination of estimates of Amgen is a standalone company along with estimates from some analysts who have already added Horizon into their estimates. So our 2023 revenue guidance is $26.0 billion to $27.2 billion, and our non-GAAP earnings per share guidance is $17.40 to $18.60 per share.
So now let me review several key points related to our guidance. For total revenue, we expect the year-over-year comparison will not include about $700 million related to several items from 2022, that we do not expect benefit from in 2023. We assume we will not generate COVID-19 antibody revenues in 2023, we also assume a lower amount of Nplate sales in 2023 compared to 2022, recall 2022, included a significant purchase of Nplate by the United States government in the second half of the year. Also several favorable changes to estimated sales deductions that occurred in 2022, and the sale of our generics business in Turkey, which closed late in 2022.
For product sales, we projected volume growth at a portfolio level, driven by strong growth in our priority products TEZSPIRE, EVENITY, Repatha, Prolia and TAVNEOS, consistent with industry trends in our recent history, we expect mid-single-digit price declines in our portfolio in 2023. Turning to Neulasta in our oncology biosimilars. We expect the recent trends to continue through 2023, this will likely result in full year Neulasta sales less than $700 million. Further, we expect less than $750 million in combined product sales for our oncology biosimilars, KANJINTI and MVASI. And finally, we expect product sales of less than $300 million for EPOGEN, as we transition through the expiry of our contract with DaVita.
For the full year, we're guiding other revenues to a range of $1.2 billion to $1.5 billion. Note that we've recognized about $300 million of revenue from our COVID antibody collaboration with Lilly in 2022, that we don't anticipate repeating in 2023. So we will continue to manage our operating expenses consistent with our historical cost discipline. So even with increasing 2023 sales volumes, declining net sales, selling prices and inflationary pressures on costs, we still project full year non-GAAP operating expenses to be flat versus 2022, as we continue our focus on driving productivity and cost efficiencies across the enterprise.
We project non-GAAP cost of sales to be in the range of 16% to 17%, as a percentage of product sales. Recall that we mentioned during our Q3 earnings discussion, that tax law changes enacted by Puerto Rico in June 2022 to replace the Puerto Rico Excise Tax, the PRET, in favor of an income tax. This change will increase our income tax expense beginning in 2023, while reducing our cost of sales by roughly an equivalent amount. Note, however, there will be a negative impact in 2023 of approximately $125 million related to the amount of the press that it's currently capitalized in inventory, that will be charged to cost of goods sold in the first half of 2023, with most of the charge recognized in the first quarter without a corresponding tax benefit.
We expect non-GAAP R&D expenses in 2023 to increase 3% to 4% year-over-year, compared to our 2022 expenses as we advanced a number of the programs Dr. Reese referenced earlier. This is consistent with our first allocate capital allocation priority to invest in the best innovation and our operating expense discipline provides us the capital to do just that. And for non-GAAP SG&A spend, we expect 2023 amounts as a percentage of product sales to slightly decrease year-over-year, driven by productivity improvements. These all lead to a projected non-GAAP operating margin as a percent of product sales of roughly 50% on a full-year basis.
We expect non-GAAP other income and expense of approximately $1.4 billion. The expected year-over-year improvement is driven by a change in our accounting for our BeiGene investment we are making in 2023. Beginning in January 2023 will no longer report our share of BeiGene results in other income and expense under the equity method of accounting on our non-GAAP income statement. We'll now mark-to-market our investment with the impact recorded only on our GAAP income statement. We expect a non-GAAP tax rate of 18% to 19%. This rate reflects the new Puerto Rico income tax, which as I explained earlier will replace the PRET, beginning in 2023.
We expect share repurchases not to exceed $500 million in 2023, and we expect that we will continue to meaningfully increase our dividend. We expect capital expenditures of approximately $925 million in 2023, consistent with our capital allocation priority to invest in our business, including in our new environmentally friendly facilities in Ohio and North Carolina. And after we complete those facilities, we expect our capital expenditures to return to their historical levels.
I'd also like to make some specific comments around the first quarter of 2023. I am encouraged that our business is performing as expected through the first month of the year. However, consistent with our historical revenue patterns, we expect revenue in the first quarter of the year to be the lowest revenue quarter of the year and slightly below revenue in Q1 2022. At a portfolio level, we expect product sales to be unchanged from Q1 2022 and other revenues to be lower on a year-over-year basis, due to the reasons set out above, including about $225 million, related to COVID antibody sales in the first quarter of 2022.
We anticipate about $80 million of foreign exchange headwinds in Q1 2023, compared to Q1 2022. The total of all these items creates greater than $400 million of headwinds versus the first quarter of 2022. So these revenue patterns along with the timing of expenses are expected to translate into our Q1 non-GAAP operating margin being below 50% as a percentage of product sales. Although, we continue to expect the operating margin as a percentage of product sales to be roughly 50% for all of 2023. Recall, this is all Amgen standalone. We will continue to focus on our legacy of execution excellence.
In summary, despite macroeconomic headwinds, we delivered another strong year of financial results in 2022, keeping us on track with our long-term commitments to delivered through 2030 and beyond. Our confidence in the long-term growth of Amgen is strong. And we look forward to completing the announced acquisition of Horizon during the first half of 2023, which will only strengthen our growth prospects. We would expect to provide updated guidance as appropriate at some point after the transaction closing.
This concludes the financial update. My thanks to our 25,000 plus colleagues at Amgen around the world for their commitment to serving patients and their tireless efforts in 2022. I'll now turn it back over to Bob for our Q&A.
