Executive Vice President and Chief Financial Officer at Bristol-Myers Squibb
Thank you, Giovanni, and thank you all for joining our call today. I'd like to start with our strong top-line performance on Slide 9. We closed out the year with another great quarter across our key franchises. Revenues grew high single digits versus prior year, which was driven primarily by increased demand for our in-line and new product portfolios.
Now let's turn to some product-specific starting with Eliquis on Slide 10. Eliquis continues to deliver extraordinary growth with global sales up 20% for both the fourth quarter and the full year. In the U.S., fourth quarter sales increased 22% versus prior year, driven primarily by total prescription growth of 13%. Internationally, Eliquis sales growth continues to be driven by increased share across all key markets and the brand remains the number 1 OAC in multiple countries. Looking forward, the growth outlook for Eliquis remains strong as we continue to grow the oral anticoagulant class and increase our share within the class. As a reminder, the first quarter of 2021 did experience a one-time favorable true-up in the U.S. of approximately $160 million that will not repeat in Q1 of '22.
Moving to Opdivo's performance on Slide 11. We are very pleased with the accelerating momentum, growing 11% globally versus prior year. This is driven by strong demand, particularly for our new launch indications. In the U.S., fourth quarter revenues were strong, up 16% versus prior year. Growth was primarily attributable to demand in metastatic indications, including first-line lung, first-line renal, and first-line gastric cancers, as well as adjuvant indications with the approvals of adjuvant esophageal and adjuvant bladder cancers in 2021.
Internationally, fourth quarter revenues grew 5% versus prior year, driven largely by demand for new indications and expanded access, primarily in emerging markets. More broadly, we continue to see uptake of our new launches in lung and renal cancer in Germany and Japan and we secured reimbursement Italy and Spain in the fourth quarter. As we look forward, we continue to expect further growth for Opdivo as we secure additional reimbursement for recent approvals. We're in a strong position to continue to grow Opdivo and look forward to additional approvals this year and in the years ahead.
Now let's turn to our IMiD portfolio on Slide 12, starting with Revlimid. Fourth quarter revenues grew 1% globally versus prior year and grew 6% for the full year with sales of approximately $12.8 billion. As we enter into the first year of generic entry for Revlimid, I want to remind you of our expectations for Revlimid sales in 2022 and beyond.
We expect Revlimid sales of $9.5 billion to $10 billion in 2022. Of these sales, we expect roughly 75% to come from the U.S. and the remaining from ex-U.S. markets. As we think about generic entry this year, we expect sales variability quarter-to-quarter based on the timing of how generic competitors fulfill their annual volumes. For the first quarter, our best projection for global Revlimid sales is approximately $2.5 billion. Beyond '22 through 2025, although there is still uncertainty due to ongoing litigation, we view an annual step down of roughly $2 billion to $2.5 billion per year as a reasonable projection.
Now on to Pomalyst. Global sales in the fourth quarter were up 2%. Sales were primarily driven by demand for triplet-based therapies in ex-U.S. markets and fewer selling days in the U.S. We continue to expect growth for Pomalyst, as treatments moved earlier lines of therapy and more triplet-based therapies are approved with longer duration of treatment. As it relates to U.S. IP for Pomalyst, we are pleased that there is now no outstanding litigation. At this point, we don't expect generic entry in the U.S. market prior to the first quarter of 2026.
Now, let's move on to our new product portfolio on Slide 13. We are very pleased with the momentum and feedback we are receiving on our new product portfolio. These products contributed over $350 million in the fourth quarter and $1.1 billion for the full year. Let me provide some color on each lines individually starting with Reblozyl, which generated global revenues of just over $550 million in 2021, more than doubling its revenues over last year.
In the U.S., full-year sales grew 87% versus prior year, primarily due to continued demand in ESA refractory MDS patients. Demand continued to grow in the fourth quarter. Sequentially, revenue was impacted by one-time favorable inventory build in the third quarter of approximately $20 million to $25 million. Our focus remains on treating new patients earlier in their treatment journey upon ESA failure, as well as ensuring physicians titrate the patients up to receive the appropriate dose for sustained benefit. Internationally, we continue to launch in additional countries and expect to continue to do so in 2022, helping more patients and driving additional growth for the brand.
Now moving to our cell therapy launches of Abecma and Breyanzi. Abecma generated revenues of $164 million since its launch in May of last year. Revenues reflect very strong demand for the first-ever BCMA cell therapy. As noted in the past, demand continues to be very robust and we're working hard to expand capacity. We expect first quarter revenues to be largely similar to fourth quarter. Turning to our CD19 cell therapy Breyanzi. Physicians continue to recognize Breyanzi's best-in-class profile for relapsed refractory patients. We look forward to moving Breyanzi up the treatment paradigm in the second-line setting with remarkable EFS data presented from our transformed study at ASH and we look forward to bringing this treatment to second-line patients in the U.S. this year.
Now moving to Zeposia. Global sales for the year were $134 million, primarily driven by multiple sclerosis indication. In the U.S. the MS launch continues to go well. Zeposia remains the leading S1P in written prescriptions and we remain focused on establishing Zeposia, not only as the S1P of choice, but also the oral treatment of choice. We continue to be pleased with the progress we have made on patient conversion, with significant decrease in time to commercial therapy.
Our early UC launch is continuing to gain traction with a leading share of voice and increased overall volume. Physicians are responding well to the profile and we are encouraged by their intent to prescribe. We are working on building volume and growing access and reimbursement. We expect to have increased contribution from UC in the second half of this year and expanding in 2023.
Internationally, Zeposia continues to gain momentum in MS as the product gets additional reimbursement in more markets and benefited from certain year-end stocking. We are very pleased with the recent EMA approval of UC in December and look forward to securing access and reimbursement for this indication to drive further growth for the brand.
Lastly, on Onureg in the U.S., we continue to make progress on establishing the product for patients with complete remission following intensive chemotherapy. Our focus remains on shaping the maintenance segment and increasing adoption and patient adherence. Overall, I'm pleased with our new product portfolio performance and look forward to three additional approvals expected this year. We are launch-ready for relatlimab and mavacamten with PDUFA date in March and April, and we're on track for deucravacitinib's launch in September.
Now, switching gears to our fourth quarter P&L on Slide 14. Having just covered sales performance, let me walk you through a few non-GAAP key line items. Operating expenses increased versus prior quarter due to timing of MS&A investments that shifted to the fourth quarter as noted in October. MS&A decreased versus prior year due to some incremental on accelerated investments to support our business in 2020. The fourth quarter effective tax rate was impacted by earnings mix and as a result, the strong performance in the quarter, non-GAAP EPS increased approximately 25% year-over-year.
Moving to the balance sheet and capital allocation on Slide 15. We continue to generate a significant amount of cash from operations with approximately $4 billion in the fourth quarter. We ended the quarter in a strong liquidity position, with approximately $17 billion in cash and marketable securities. Our capital allocation priorities remain unchanged. Business development remains our top priority to further renew and diversify our portfolio and we are also focused on reducing debt and returning capital to shareholders. We have executed several business development deals last year, bringing in differentiated early-stage assets.
We have the financial strength to be size-agnostic, but we are particularly interested in early science and mid-sized bolt-on deals. As it relates to debt in 2021, we reduced gross debt by over $6 billion and remain committed to maintaining a strong investment-grade credit rating. Lastly, as it relates to returning capital to shareholders, we recently grew the dividend by over 10%, which was our 13th consecutive increase. Additionally, we increased our share repurchase authorization by $15 billion and plan to execute a $5 billion ASR this quarter.
Now turning to our 2022 non-GAAP guidance at current exchange rates on Slide 16. As announced last month, we expect '22 revenues to be approximately $47 billion, representing low single-digit growth over 2021. Growth from our continuing business will more than offset the revenue impact from Revlimid and Abraxane LOEs.
We expect key LOE brand sales to be approximately $10.5 billion and our continuing business, which represents our in-line and new product portfolios is expected to grow low-double-digit and contribute approximately $36.5 billion. As it relates to our line item guidance for the year, we expect our gross margin to be approximately 78% and our total operating expenses to be in line with 2021 expenses and we project our tax rate to be approximately 16.5%.
Finally, also communicated earlier this year, we expect non-GAAP EPS to grow faster than sales and be between $7.65 and $7.95. As it relates to our share count, I'd like to provide a little color as we plan to execute the $5 billion ASR. We ended the year with approximately $2.2 billion diluted shares outstanding. We will be executing ASR later this quarter, which means we will get a majority, but not all of the benefit on diluted share count this year.
Lastly, given this is the first quarter of generic entry for Revlimid, we thought it'd be helpful to provide some perspective on revenue for the first quarter. In addition to the approximately $2.5 billion of Revlimid sales, I mentioned previously, we are projecting total global first quarter sales to range from $11 billion to $11.5 billion. So before I turn it over to question and answer. I just want to thank our teams around the world for delivering these remarkable results in 2021. These results and our guidance for 2022 demonstrate the financial strength of the business and the renewal of our portfolio, which positions us well for long-term growth.
I'll now turn the call back over to Tim and Giovanni for Q&A.