Pablo J. Cagnoni
President and Head of Research and Development at Incyte
Thank you,, and good morning. As we highlighted a year-ago and we summarized on this slide, we remain on-track to deliver more than 10 high-impact launches by 2030 from programs across the portfolio. On Slide 15, I would like to quickly highlight some of the key accomplishments during 2024 and I will then cover some of the milestones expected in 2025. We had a number of important regulatory achievements in 2024, including the approval of for third-line plus chronic ref versus host disease and three submissions to the FDA with expected approvals later this year, including Opzelurin pediatric atopic dermatitis, retifanlimab in SCAC and tafasitamab in relapsed or refractory follic lymphoma. We disclosed data from our CDK2 inhibitor and BET inhibitor programs and provided pivotal study plans for both, which we anticipate initiating this year.
We continue to evolve at R&D focus with intent of increasing the rigor of our decision-making, accelerating the progression of our pipeline and optimizing our resource allocation. Through the 4th-quarter of 2024, we presented data at the American Society of Hematology Annual Meeting or ASH from both our BET inhibitor program and Phase-3 results for in-patients with relapsed or refractory lymphoma. The Phase-3 results of tafacitamab in follicular lymphoma were presented at a late-breaking session and show that the study met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival. This was to our knowledge, the first study to validate the combination of an anti-CD19 with an anti-CD20 monoclonal antibodies in-patients with follic or lymphoma. Was generally well-tolerated and safety was consistent with its known safety profile. This data have been submitted to the FDA and approval is expected in the second-half of 2025. Thank you.
For our BET inhibitor, we shared additional data from the ongoing dose-escalation study as both monotherapy and in combination with ruxolitinib. These results show reductions in spleen volume as well as improvement in both symptoms and hemoglobin. As highlighted on this slide, we plan to advance this program into Phase-3 development as a monotherapy in the post-JAK population and we look-forward to providing additional details later this year. Moving to Slide 18, we are continuing to execute a broad development plan for povorcitinib, our oral small-molecule highly selective JAK1 inhibitor. Is currently being evaluated in Phase-3 studies in suprativa, vitiligo and nodularis and in randomized Phase-2 proof-concept studies in chronic spontaneous and asthma with data for both expected in 2025. Has already shown encouraging efficacy and safety in a randomized Phase-2 study in-patients with moderate-to-severe, a highly painful inflammatory condition.
As highlighted on this right-side of the Slide 19, showed significant responses by week-12, including improvements in high score 50, 90 and 100. Additionally, demonstrated a rapid and significant reduction in pain, offering the potential to transform the current standard-of-care for this disease. The two Phase-3 studies, STOP ages 1 and STOP ages 2 are fully enrolled and we expect to have Phase-3 data in the first-half of this year. Turn to the mutant cholear antibody program on Slide 20. The publication detailing our mutant color monoclonal antibody was recently featured on the cover of blood, highlighting the importance of this innovative medicine. This antibody was developed entirely by Insight and unlike Jakafi, the mutant color antibody has the potential to eliminate the mutant clone and normalize hematopoiesis in-patients with mutated essential thrombocytemia or myelofibrosis, potentially leading to a functional cure. We look-forward to sharing data from the ongoing proof-of-concept studies in both ET and MF later this year.
Turning to Slide 21 and ruxolitinib XR. We're pleased to announce that a bioequivalency study of ruxolitinib 55 milligrams extended-release demonstrated the once-a-day formulation to be bioequivalent to twice a day ruxolitinib. By equivalence was achieved for both AUC and and the geometric means ratios falling within the 80% to 125% by equivalence reference range. We have reviewed this data with the FDA and with their agreement, plan to submit for approval by the end-of-the year once stability studies are completed. Thank you. As mentioned, 2025 will be an important year for Insight with over 18 key milestones, including four new product launches, four pivotal trial readouts, at least three Phase-3 study initiations and seven proof-of-concept study results.
As you can see on Slide 22, we have already achieved two of these milestones that we first highlighted just last month with the launch of and bioequivalency data for ruxolinib extended-release. We look-forward to sharing additional updates on these milestones over the course of 2025. And with that, I would like to turn the call over to Christiana for the financial update. Thank you, Pablo, and good morning, everyone. Our 4th-quarter 2024 results reflect strong commercial execution and continued growth with total revenues of $1.2 billion, up 16% versus the same-period last year. Total product revenues of $1 billion in Q4 were driven by strong demand growth for Jakafi and Opzelura and increased revenue contribution from Monjuvi as a result of the acquisition of full rights to dafacitamab in 2024. Total royalty revenues were $159 million, up 6% compared to Q4 2023, driven by increased demand for Jakavi. Thank you.
Turning to Jakafi on Slide 26. Jakafi net product revenue was driven by strong patient demand growth across all indications. In the 4th-quarter of 2024, net product revenue increased 11% year-over-year, driven by a 9% increase in total demand and a 14% increase in pay demand. For the full-year 2024, net product revenue increased 8% versus 2023, driven by a 7% increase in total demand and a 9% increase in paid demand. Recall that in Q3 and Q4 2023, we saw a significant increase in the number of Medicare Part-D patients receiving free product. As we anticipated, these patients returned to pay demand in 2024. As a result, year-over-year pay demand growth exceeded total demand growth in both the 4th-quarter and full-year 2024.
Thank you turning now to Opzelura on Slide 27, total net product revenue for the 4th-quarter was $162 million, representing a 48% increase year-over-year, driven by growth in new patient starts and refills across both AD and vitiligo in the US as well as continued contribution from the commercialization of Opzelura for vitiligo in Europe. In the 4th-quarter, ex-US Opzelura net product revenue was $24 million. For the full-year, net product revenue was $508 million, representing a 50% increase year-over-year and ex-US net product revenue was $61 million. Thank you. Moving on to Slide 28 and our operating expenses.
Total GAAP R&D expenses for the 4th-quarter were $466 million, an increase of 5% compared to the same-period in '23 due to continued investment in our late-stage development assets and timing of certain expenses., for the full-year 2024, ongoing R&D expenses, excluding the Asiant acquisition upfront to consideration and other one-time expenses increased 14% year-over-year as a result of increased investment in our late-stage programs., as we wrap-up the clinical developments of certain of these programs as well as the development activities of discontinued programs, we anticipate the reduction in investment in those programs to partially offset the increased investment in other programs, which would allow us to control future R&D expense growth. Thank you.
Moving to SG&A, total GAAP SG&A expenses were $327 million for the 4th-quarter, representing an 11% year-over-year increase, primarily as a result of Insight now recording Monjuvi related sales and marketing expenses in the US following the acquisition of global rights to the program in 2024, as well as the timing of consumer marketing activities and certain other expenses. For the full-year 2024, total GAAP SG&A expenses increased 7% year-over-year as a result of us now recording Monjuvi related sales and marketing expenses and investment in the launch of Opzelura in Europe and the preparation for new product launches in the US. Finally, total ongoing R&D and SG&A expense for the full-year increased 10% versus a 15% increase in total revenues, leading to an increase in operating leverage and margins.
Moving on to 2025, I will now discuss the key components of our guidance on a GAAP basis. For Jakafi, we expect net product revenue to be in the range of $2.925 billion to $2.975 billion, well on-track to achieve our long-term guidance of over $3 billion by 2028. We expect net product revenue growth to be driven exclusively by continued demand growth, primarily in PV and be partially offset by lower net pricing as a result of IRA imposed price increase caps and continued growth in 340B volumes. As in previous years, we expect the gross-to-net adjustment to be higher in the first-quarter of the year relative to the previous quarter and subsequent quarters due to higher deductibles that are primarily impacting Q1.
For Opzelura, we expect total net product revenue to be in the range of $630 million to $670 million, driven by continued demand growth in AD and vitiligo in the US, initial contribution from the potential launch of Opzelura for pediatric AD expected in the second-half of the year and increased contribution from Opzelura for vitiligo in Europe. In the first-quarter of the year, we expect to see again the effects of typical Q1 dynamics on-net sales due to planned deductibles resetting at the beginning of the year and the impact of holidays, medical conferences and other events on dermatology product sales. As a result, Q1 Opzelura net product revenue is expected to be below the previous quarter, consistent with what we saw in 2024.
For other oncology products, we expect total net product revenues to be in the range of $415 million to $455 million. These includes contribution from both the current approved indications for Iclusic, Monjuvi Minjuvi, and Zinese as well as the launches of Monjuvi NFL and in CAC anticipated in the second-half of 2025. Turning to operating expenses on a GAAP basis, we expect COGS to range from 8.5% to 9% of net product revenues. The increase in the COGS rate is driven by certain manufacturing-related expenses and the impact of our profit share agreement with Syndax for in the US as Syndax's portion of the profit share will be reflected in COGS. R&D expenses are expected to be in the range of $1.93 billion to $1.96 billion, primarily driven by the progression of our pipeline.
We expect SG&A expenses for the year to be in the range of $1.28 billion to $1.31 billion. Thank you. Operator, that concludes our prepared remarks, please give your instructions and open the call for Q&A.
