Good morning, and welcome to the Karyopharm Therapeutics First Quarter 2022 Earnings Conference Call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Elhan Webb, Senior Vice President, Investor Relations. Please go ahead.
Thank you, Debbie, and thank you all for joining us on today's conference call to discuss Karyopharm's first quarter 2022 financial results and recent company progress. Today I'm joined by Richard Paulson, President and CEO, Sohanya Cheng, Chief Commercial Officer, Dr. Reshma Rangwala, Chief Medical Officer, Dr. Patricia Judson, SVP, Medical Strategy, and Mike Mason, Chief Financial Officer. This morning, we issued a press release detailing Karyopharm's financial results for the first quarter 2022. This release, along with a slide presentation that we will reference during today's call, are available under the Events and Presentation section of our website at karyopharm.com. For today's call, as seen on slide two, Richard will provide some opening remarks. Sohanya will provide a commercial update for XPOVIO, then Reshma and Patricia will provide an update on the clinical development programs.
Mike will then provide an overview of the financial highlights from the quarter, and Richard will provide some closing remarks before opening the call up for questions. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide three. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC, and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only.
While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. In addition, we will also be providing on this call outlook for non-GAAP R&D and SG&A expenses for 2022. We are not providing reconciliations of these forward-looking non-GAAP measures because projections of stock compensation expense, which is required for such reconciliations, are not available without unreasonable efforts. I will now turn the call over to Richard. Please start the slides.
Thank you, Elhan, and good morning to everyone joining us on the call and webcast today. Q1 was another strong quarter, and I'm very excited to provide an update on our plan as we continue to execute on our growth strategy through our focused commercial execution and pipeline development that we are pursuing on behalf of patients in need. On slide five, we have an overview of the key pillars that drive our underlying value and provide opportunity for what we believe will be substantial future growth. First, we are successfully building upon our existing multiple myeloma franchise. This quarter, we generated strong revenues and expect to continue strong sales in 2022 through focused execution and proven commercial capabilities, creating value for both patients and shareholders.
On the global regulatory front, we are expecting the European CHMP to complete its review of the selinexor application in second-line plus and issue an opinion during the first half of 2022. Together with our global commercialization partners, we are increasingly bringing XPOVIO to patients worldwide. Second, shifting from our multiple myeloma franchise to our focused pipeline, where we continue to make strong progress. We are advancing a clinical pipeline comprised of mid- and late-stage clinical development programs that is being purposefully built and strategically focused on targeting cancers with high unmet need, where our science enables us to make the biggest difference in the lives of patients and in areas with high probability of success. To that end, we are pursuing approval opportunities in multiple myeloma, endometrial cancer, myelofibrosis, and myelodysplastic syndromes over the next 2 years-4 years.
Our third pillar is our people, and we strengthened the leadership team during the first quarter. We believe we have the right people in place who have exceptional abilities to achieve both scientific and commercial excellence while executing on our key corporate objectives. Fourth, and finally, to support our strategic and focused growth plan, we are well capitalized and expect to be able to fund our operations into early 2024. At Karyopharm, everything we do is driven by our mission to positively impact patient lives and defeat cancer. Our foundation is in our science, and we are the global leader in the inhibition of nuclear export. Against this backdrop, we believe we have a strong organization which allows us to execute this year and beyond.
The first quarter of 2022 was marked by several meaningful achievements, as outlined on slide six, including continued robust commercial performance and significant progress across our pipeline. To start, we achieved total revenues of $47.7 million, which included $19.4 million from certain license and milestone revenues as our footprint expands globally. Second, XPOVIO delivered strong year-over-year growth in the U.S. during the first quarter, achieving $28.3 million in net product revenue, representing year-over-year growth of 30%. We achieved these results through continued increasing uptake in the second through fourth line, with strong growth in the third line and despite COVID-related headwinds experienced during January and February. For global commercialization efforts, XPOVIO or NEXPOVIO is now approved in 37 countries, the most recent of which are mainland China, Australia, and Singapore through our partner, Antengene.
In endometrial cancer, we recently reported top line results from the phase III SIENDO study, where selinexor showed especially encouraging results in the exploratory subgroup of patients with p53 wild-type tumors, improving PFS by an impressive 10 months, and we are planning to initiate a registrational phase III study in the second half of this year. We'll be presenting results at the upcoming ASCO 2022 annual meeting, including results from a subgroup and molecular analysis from the SIENDO study, and the preliminary clinical results from our phase I/II study investigating selinexor combined with ruxolitinib in patients with treatment-naive myelofibrosis. Last but not least, on the corporate front, we recently strengthened the leadership team with Dr. Reshma Rangwala joining us as Chief Medical Officer.
We are delighted to have her join the team, and we believe that her extensive experience developing and executing clinical strategies for novel oncology therapeutics, as well as engaging regulators and the medical community at all stages of development, will be of immeasurable value as we accelerate our four core programs in clinical development as shown on slide seven. Our drive, vision, and innovations, along with the scope and range of data generated to date, have led us to focus on our four core programs shown here. Multiple myeloma, endometrial cancer, myelofibrosis, and myelodysplastic syndromes. Along with all of these being areas of high unmet need for patients, each has a significant addressable market. A key focus of today's call will be our endometrial cancer and myelofibrosis programs.
As we turn now to slide eight, I would like to turn the call over to Sohanya for her review of the commercial performance for the quarter. Sohanya?
Thank you, Richard, and good morning, everyone. Since our launch, we continue to focus on expanding the potential of XPOVIO and its benefit to patients in earlier lines. Slide nine shows how we have evolved from our original approval of Xd based on the STORM study to gaining FDA approval for the XVd regimen based on our BOSTON study, and now to initiating a phase III study with selinexor, pomalidomide, and dexamethasone, an all-oral triplet combination which Reshma will expand on later. In this process, we have evolved from twice-weekly to once-weekly, from higher to lower doses, from a doublet to triplets, expanded into earlier lines with multiple combinations, and improved the overall patient experience. We've achieved all of this during challenging times. With the ebbs and flows of COVID, the team has done outstanding work to adapt quickly, focus on head-down execution, and continue to drive strong results.
Turning now to slide 10 on our commercial highlights for the first quarter of 2022. It's rewarding to continue to see patients being treated in earlier lines and staying on therapy longer. Despite the impact of COVID in the first quarter of this year, we grew net product revenue by 30% versus the same period last year and continued to make excellent progress across key indicators since our second-line plus launch at the beginning of 2021. In addition, inventory levels were consistent with the last quarter. The environment was particularly challenging with the surge of COVID in January and February, which impacted oncology patient visits and new starts, as well as our access to healthcare providers. We did see a recovery in March with patient visits starting to normalize, our new starts growing, and our access to physicians improving.
We continue to make strong progress with our primary growth driver and what we believe is most important to patients, which is the positive shift in earlier lines. This shift into earlier lines, as well as continued education to improve tolerability, has resulted in more patients staying on therapy longer. We are also expanding in the breadth and depth of use of XPOVIO, with strong growth in the community setting. While we continue to grow our breadth by adding more accounts every quarter and penetrating in more top myeloma accounts, as we progress through our launch phase, our focus is now on growing depth with our core customer base by increasing new patient starts and driving the shift into earlier lines, where patients are more likely to stay on therapy longer, thus generating more refills in the future.
We believe the beneficial impact to patients and growing confidence among our physicians in using the lower dose once-weekly XPOVIO-based triplet regimens are seen in the data. Our intent to prescribe data continues to show sustained improvement in the efficacy and safety perception of the product in the third line. We remain confident about guidance we provided for 2022 net product revenue of $135 million-$145 million. We see strong and consistent momentum across all our growth drivers, increasing confidence amongst physicians in using XPOVIO, and we have a field team that is laser-focused and committed to bringing XPOVIO to more patients in the second to fourth line. With regards to COVID, we continue to see the environment normalizing and will monitor and adapt as things evolve.
The unmet need remains strong for new modalities like XPOVIO because in multiple myeloma, physicians' ability to class switch with multiple combinations has driven significantly better patient outcomes. A majority of treated patients in the first to second line are exposed to an anti-CD38 therapy. Many of these patients' diseases will become refractory to or relapse from an anti-CD38 treatment. We believe this is where XPOVIO is a strong fit in the second to fourth line. It is a novel class of therapy with robust efficacy and with a breadth of data in the post-anti-CD38 setting. It has a well-understood and manageable safety profile, and while we only promote FDA-approved regimens, physicians have the option to combine with several different backbones per the NCCN guidelines.
Building on our momentum in 2021 and early this year, and with a rapidly advancing myeloma pipeline, we expect to continue to drive a steady growth in the near, mid, and long term. With that, please advance to slide 11, and I'll turn the call over to Reshma and Patricia to review our clinical pipeline progress.
Thank you, Sohanya. It's great to be here today, just under three weeks after I joined Karyopharm as chief medical officer. Before discussing our pipeline, I'd like to take a moment to introduce myself. I'm a medical oncologist with more than a decade of experience in oncology drug development, both at large pharmaceutical companies and at smaller developmental stage companies. Prior to joining Karyopharm in mid-April, I spent 10 years in roles with increasing responsibility at three life science companies, including Aravive, Genmed, and Merck. During my career in industry, I have participated in the development of multiple oncology drugs with varying mechanisms of actions, including immuno-oncology agents and antibody- drug conjugates across all phases of drug development— from IND filings for phase I to designing and implementing registrational studies leading to successful first approvals as well as additional major indications.
In addition, I have participated in the development of companion diagnostics, including a PD-L1 IHC. I can see that both selinexor and eltanexor have significant potential for battling an array of cancer types, and I am thrilled to join the Karyopharm team at such an exciting and pivotal time in the company's growth. I'm impressed with both the team and the science of XPO1 inhibition, and I am excited to realize the potential of these therapies for patients that are being evaluated in our four core programs. Now, turning to slide 12, I will be reviewing our clinical development pipeline from our four core programs. As we look to the future on slide 13, one of our top priorities is to expand our footprint in multiple myeloma, both in the U.S. and across the globe. We have strategically partnered selinexor in key ex-U.S. territories.
Our partner, Antengene, recently obtained approvals, which include conditional and full approvals for XPOVIO in mainland China, Australia, and Singapore. For Europe, the application requesting approval for selinexor in patients with multiple myeloma following at least one prior therapy has been validated and is currently under review by the CHMP. The outcome of the CHMP review is expected by the end of the first half of 2022. There are also pending marketing approval applications for second-line plus multiple myeloma submitted or on file in Canada and other Asia-Pacific markets through our strategic partners. Turning now to slide 14 and some updates from our developmental pipeline. I'll start first with multiple myeloma.
In addition to the work Sohanya and her team are doing on the commercial front in the U.S. and the work our global partners are doing on the regulatory front. We are also working to obtain additional clinical data in order to expand into additional multiple myeloma patient populations where selinexor may provide benefits. To that end, we are initiating a global registration-enabling randomized phase III study in the first half of 2022 that is designed to evaluate the SPD triplet regimen in patients with multiple myeloma following at least one prior line of therapy, including an anti-CD38- based regimen. SPD will be an all-oral regimen, which is highly desirable with this patient population, with over half of the patients in second line being an oral containing regimen.
This is building on our STOMP data, which showed robust efficacy and good tolerability, and is paired with the well-established backbone of pomalidomide, which is widely used in earlier lines. As you can see from our study design, SPD will be evaluated against the triplet combination of elotuzumab, pomalidomide, and low-dose dexamethasone, or EPd. I will now turn the call over to Patricia to review the endometrial cancer and myelofibrosis programs, which begin on slide 15.
Thank you, Reshma. First, I'll provide an overview of the unmet need in endometrial cancer and why we find our upcoming opportunities so exciting for patients. Endometrial cancer is the most common form of gynecologic cancer in the United States. Unlike other solid tumors, endometrial cancer mortality continues to increase. Of the 14,000 patients diagnosed with advanced or recurrent endometrial cancer each year in the U.S., approximately 50% have p53 wild-type tumors. The current landscape for advanced or recurrent endometrial cancer consists of first line chemotherapy, where response rates are approximately 70%. However, following responses to chemotherapy, there are no effective treatments available, and the NCCN guidelines recommend a watch and wait approach until disease progression. This approach clearly needs improvement because the five-year survival is only 17%.
As selinexor is administered orally and maintenance therapy is well established with physicians that treat multiple types of solid tumors, including breast and ovarian cancer, we believe selinexor has the potential to offer these patients a new maintenance option that could sustain the response from chemotherapy and help keep cancer from returning for longer. As you know, we recently reported results from the phase III SIENDO study. A subset in this study, which is shown on slide 16, demonstrated single agent selinexor to have an impressive 10-month improvement in median PFS in a pre-specified exploratory subgroup of 103 patients who had p53 wild-type endometrial cancer. The patients in this study were diagnosed with advanced or recurrent endometrial cancer. They were treated with frontline chemotherapy and had either a partial or complete response to chemotherapy.
In patients with p53 wild-type disease, the selinexor-treated patients achieved a median progression-free survival of 13.7 months, compared to just 3.7 months in the placebo-treated patients. Based on these exciting data, we are partnering with opinion leaders, the Gynecologic Oncology Group, and the European Network of Gynaecological Oncological Trial , or ENGOT, to initiate a registration-enabling phase III study, which we plan to initiate during the second half of 2022. I would now like to highlight our rapidly advancing myelofibrosis program and the current treatment landscape. If you turn to slide 17, please. Ruxolitinib is the current standard of care for newly diagnosed myelofibrosis. However, approximately 40% of patients respond to frontline treatment, leaving 60% of patients requiring subsequent therapy. For patients who respond initially to ruxolitinib, the response rates can be up to 4 years.
Once patients stop responding, the expected median survival is approximately 14 months, and the 5-year survival rate is only 18%. There are no other drug classes other than the JAK inhibitors currently approved or have been approved in the last 10 years. On slide 18, I will review the strong single agent data that we generated in our phase II ESSENTIAL study, which looked at single agent selinexor in patients after a JAK1/2 inhibitor. 40% of patients in this study achieved a spleen volume reduction of 35% or greater following at least 24 weeks of treatment. The 2-year probability of survival was 92%. To put these data into context, currently available therapies in a similar patient population lead to spleen volume reductions of 35% or greater in approximately 15% of patients.
Furthermore, in the ESSENTIAL trial, we observed positive impacts on hemoglobin levels, including 50% of patients achieving either improved hemoglobin levels or transfusion independence. The hemoglobin increased by at least two grams per deciliter in 67% of patients. Again, contrast this with other agents in which anemia often worsens on therapy. In this study, selinexor was generally well-tolerated with a median treatment duration of 11 months. A range of 2.8 months to an impressive 28.8 months. The ESSENTIAL study is small and has early data, but you can see why we are excited about the potential of our two ongoing studies.
We believe that selinexor, as a novel class of therapy, has the potential to improve outcomes for patients with multiple possible benefits, including durable spleen volume reduction, improvement in anemia status, the potential to decrease symptom burden by decreasing the inflammatory cytokine profile and disease modification. Turning now to slide 19, we have our most advanced myelofibrosis study, the ongoing phase II MF-035 study, which is a randomized open label study evaluating single agent selinexor versus physician choice therapy in patients with myelofibrosis who have had at least 6 months of prior treatment with a JAK1/2 inhibitor. The primary objective of this study is to assess SVR35, and key secondary endpoints include TSS50, overall response rate, overall survival, anemia response, impact on symptom burden and safety.
We dosed our first patient in this study last year and expect to report top line data during the second half of 2023. Turning now to slide 20. This is our frontline myelofibrosis study, a phase I/II study evaluating the combination of selinexor and ruxolitinib in patients with treatment-naive myelofibrosis. Our goals for this study are to explore the combination of selinexor and ruxolitinib, building on the single agent activity of both compounds. Given the potential synergism between these two drugs, we believe that the combination of Seli and Rux have the potential to improve upon efficacy parameters while maintaining or improving symptom burden. This study began in mid-2021, and we are excited to be presenting the preliminary phase I data at the upcoming ASCO 2022 annual meeting.
With that, I'm now going to advance to slide 21 and turn the call over to Mike to review the first quarter financial highlights. Mike?
Thank you, Patricia. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights which begin on slide 22. Total revenue for the first quarter of 2022 was $47.7 million, compared to $23.3 million for the first quarter of 2021. Net product revenue from U.S. commercial sales of XPOVIO for the first quarter of 2022 was $28.3 million, compared to $21.7 million for the first quarter of 2021, representing a 30% increase year-over-year. The estimated gross-to-net discount for XPOVIO in the first quarter was 19%. We expect gross-to-net discount to be in the 15%-20% range for the full year 2022.
We recognized $19.4 million of license and milestone revenue in the first quarter of 2022, which is inclusive of $8.6 million related to milestones earned in connection with our license agreements with Antengene and Promedico, and $7.1 million earned in reimbursement of development expenses from the Menarini Group. As a reminder, as part of the agreement that we announced in December, Menarini reimburses us for 25% of all expenses that we incur for the global development of Selinexor, not to exceed $15 million per year. R&D expenses for the first quarter of 2022 were $42.1 million, compared to $37.1 million for the first quarter of 2021. This increase is primarily attributable to higher clinical trial expenses, including start-up costs for the phase III SPD study for the first quarter of 2021.
Cash, cash equivalents, restricted cash and investments as of March 31, 2022 totaled $207 million, compared to $235.6 million as of December 31, 2021. Based on our current operating plans, we continue to expect net product revenue of $135 million-$145 million for 2022, reflecting approximately 40% growth compared to 2021. Non-GAAP, R&D and SG&A expenses, which excludes stock-based compensation expense to continue to be in the range of $265 million-$280 million for the full year of 2022. Certain previously expected launch preparation costs for endometrial cancer, which were included in our SG&A guidance, were shifted to R&D for the new SIENDO-II study.
Therefore, we expect non-GAAP R&D expenses to decrease by approximately 10%, including the cost of the SIENDO-II trial compared to 2021, with most of the decrease expected to occur in the second half of 2022. Finally, that our existing cash equivalents, and investments, as well as the revenue we expect to generate from XPOVIO product sales and other license revenues, will be sufficient to fund our planned operations into early 2024. I'll now flip to slide 23 and turn the call back to Richard for some final remarks.
Thanks, Mike. We believe that we are well-positioned for a strong 2022, both on the commercial front as well as with the advancement of our clinical programs. We continue to maintain strong momentum with a number of key near-term catalysts and corporate milestones for us to deliver on, as outlined on slide 24, as we continue to strive each day for patients with high unmet needs. The key upcoming milestones we are focused on over the near term, in addition to our continued focus on driving commercial performance, are to dose the first patient in our phase III study evaluating the all-oral SPD triplet in patients with relapsed or refractory multiple myeloma by the end of the first half of 2022.
Receive a decision from the CHMP on our application requesting approval for selinexor, bortezomib, and dexamethasone in patients with multiple myeloma following at least one prior therapy, also during the first half of 2022. For the endometrial cancer program, we will be presenting subgroup and molecular analysis data from the SIENDO study in an oral presentation at ASCO 2022. We are also planning to initiate a new registration-enabling phase III study in p53 wild-type tumors during the second half of 2022. For the myelofibrosis program, we look forward to presenting top-line phase I selinexor data in combination with JAK inhibition in treatment-naive myelofibrosis, also at ASCO 2022. Finally, for the MDS program, we expect to report preliminary phase I eltanexor data in combination with a hypomethylating agent in frontline MDS during the second half of 2022.
In closing, I would like to give a heartfelt thank you to all our teams at Karyopharm and our investigators as we work every day to positively impact the lives of patients with cancer. We would also like to thank our shareholders for your ongoing support and look forward to keeping you updated on our continued progress. It's an exciting time for the company, and we are all diligently working to create value for all of our many stakeholders. With that, I would now like to ask the operator to open the call up to the question and answer portion of today's call. Operator?
We will now begin the question and answer session. To ask a question, you may press Star, then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press Star then two. At this time, we will pause momentarily to assemble our roster. First question comes from Maury Raycroft with Jefferies. Please go ahead.
Hi, good morning, and thanks for taking my questions. First one is on myelofibrosis with the upcoming data at ASCO. Can you talk about how many patients or what kind of follow-up we might see at ASCO? Maybe talk more about how you're looking for selinexor plus ruxolitinib for this combo to differentiate from some of the other ruxolitinib combos in the clinic.
Yeah. Thanks, Maury. For the first part of that, you know, I'll pass it over to Patricia to talk about what we expect to see at ASCO and also, you know, what we expect to see in combining Rux with Selinexor in the frontline myelofibrosis. Patricia?
Yeah, thanks. We're really excited about the preliminary data that we're gonna be reporting at ASCO in about a month. This is gonna be the phase I portion of the ongoing phase I/II trial that obviously is looking at selinexor in combination with ruxolitinib in patients with treatment-naive myelofibrosis. Obviously we'll share more details when the ASCO abstracts are released on May 26th. What we're hoping to see with this combination, anytime you combine two agents with strong single agent activity, we look to improve on the efficacy and still have a tolerable side effect profile. As I reviewed during the presentation, you know, in the ESSENTIAL trial with monotherapy selinexor, we saw really durable spleen responses. 40% of patients achieved an SVR35 at 24 weeks or greater. In the ruxolitinib trial, 40% of patients achieved SVR35. Therefore, the combination should be higher than this.
Got it. That's really helpful. Also wanted to ask a question about myeloma too. For proportion of patients being prescribed in early versus later lines, it seems like that's been at about 50/50 for a few quarters now. Are you seeing this start to shift more toward earlier lines? Can we learn more about that this year over the next couple quarterly updates?
Yeah. Thanks, Maury. I'll turn to Sohanya to take you through that.
Thanks, Maury, for the question. Yes, we continue to see that steady shift into the second to fourth line. We see now greater than 50% of our patients now in the second to fourth line versus the fifth line plus. The good news is the patients are seeing the benefit here and are staying on therapy longer. We're seeing an increasing proportion of patients, for example, staying on four cycles or greater, and you're seeing this benefit because of the earlier line shift, primarily.
We'll continue to update on that as we move forward, Maury, during the year.
Okay. Okay, very good. Thanks for taking my questions.
Thank you.
The next question is from Peter Lawson with Barclays. Please go ahead.
Hey, thanks for taking my questions. I guess the first one's just around the impact of COVID. Is there any way, maybe Richard or Mike, to kind of break out the impact of COVID in the first couple of months of the quarter?
Thanks, Peter. I'll let Sohanya do that because it's pretty clear as she looks at some of the numbers. Sohanya?
Yeah. Thanks, Peter. You know, overall when you think about COVID impact, there's a couple of different facets, right? Particularly challenging environment in Q1, but when you look at January and February in particular, the data shows that COVID had up to approximately a 10% negative impact on oncology patient visits in Q1 of 2022. Now that in turn impacted our new patient starts in that January to February period. The second component in terms of COVID impact is field activity and access to physicians. This was impeded in that January to February period, including our proportion of live engagement. As you know, in the initial stages of a launch, it's critical to have this time in front of customers.
However, in March, we saw the trends improving, both in the marketplace. We're seeing signs of patients returning back to the clinic, but more importantly, our access to physicians improved in March with over 60% of our engagements being live. Also, we grew our new starts in March as well. If you take a step back and look at our growth drivers holistically, we sustained improvement across all our growth drivers. We continue to see that positive shift in early line, which gives us the duration benefit. We continue to increase our breadth, but more importantly, our depth of use of XPOVIO, and we also improved our position per the intent to prescribe data.
Thank you. Then it's encouraging to see the revenue guidance reiterated. What factors should we be thinking about that help reaccelerate quarter-over-quarter growth and also drive higher year-over-year growth? What are the factors there and how should we think that kind of playing out through the year?
Thank you, Peter. I'll turn that over to Sohanya in a minute. As you know, there's obviously those dynamics that happen quarter-over-quarter. So focusing obviously on reiterating our guidance and achieving that range of about 40% growth over the year. I think Sohanya has talked about some of those headwinds we faced already in Q1. I'll turn to Sohanya to kind of take you through why we have the confidence to deliver on that for the full year.
Great. Thanks, Peter. First of all, 30% year-over-year in net product revenue growth. I feel extremely good about it, given the backdrop of the significant COVID impact we experienced, particularly in the January-February phase. In terms of moving forward and the growth drivers, they remain the three key growth drivers where we've seen sustained improvement. Our focus for the rest of this year is to accelerate that earlier line shift. We've seen our most rapid growth in the third line, and our focus is to continue to accelerate that third line growth. As I mentioned earlier, you see as a result the benefit on duration when these patients move into earlier line.
I think the second area of focus is we've talked about breadth and depth, but as we evolve through our launch phase, our focus becomes accelerating depth. To give you an example of depth and increase in the use of XPOVIO with our core customer base, if you look at our top 20 XPOVIO accounts, which include a lot of the major community networks, and they contribute to about 1/3 of the business, we saw almost 50% revenue growth. For the rest of this year, with the access improving to our physicians, driving depth will be a critical success factor. Finally, improving the perception of the product. We've seen continued sustained improvement over the course of the year, and we plan to continue to do that, in terms of improving perception of both the efficacy as well as the safety.
In terms of, Richard pointed out too, there can be quarter-over-quarter fluctuations. Typically, they're in Q4, Q1, you see some seasonality dynamics, some buying pattern dynamics in Q4. When you think about Q2 and moving forward, we anticipate the marketplace normalizing in terms of patient flow, obviously excluding any potential future COVID impacts. I feel confident about our annual guidance of $135 million-$145 million.
Are there any clues from the either the scripts or the access or patient flow for April as well? Did that get better over March? Final question.
Yeah. Well, I think we'll comment on that as we get into Q2. I think we just wanna focus on Q1 now because it takes a while, obviously, for that data to mature and see what it looks like.
Got you. Okay. Thank you so much.
Thanks, Peter.
The next question is from Michael Ulz with Morgan Stanley. Please go ahead.
Hey, guys. Thanks for taking the question. Just given that you're seeing some impact of COVID on the commercial side, just curious if you're seeing any impact on the enrollment side, specifically for your phase II MF and MDS studies.
Yeah. Thanks, Mike. I'll hit that at a high level, and then I'll turn it over to Reshma. I think as we all experienced in the environment in January and February, you know, a number of staff were out across our clinical trial sites, so that did affect some of our startups. It did affect some of the access in different areas. Reshma, maybe you want to expand on that a little bit?
Yeah, we see that. Thank you for the question. I mean, we see some of the challenges with COVID.
In our clinical trials as well. We've had issues with sort of resources, ability to get to sites, challenges in opening up the sites, you know, at our facilities. You know, with that said, you know, hopefully, we should be, you know, seeing a turnaround and continued enrollment and potentially expanded enrollment in all of our studies.
Got it. That's helpful. Maybe just one more question from me and a follow-up just on the MF data that you're expecting at ASCO next month. In terms of the bar, when we think about the data, you mentioned, you know, 40% is kinda what to expect for Rux. In combination, you should be above that. As you think about moving this program forward in the future, what, you know, what's meaningfully above, you know, 40%? You know, is it 10 percentage points? Is it more than that? Or just, you know, can you provide some color there, that would be helpful. Thanks.
Yeah. Thanks, Mike. I'll turn to Patricia to talk to that. I think there's a number of areas that Patricia will touch on. One is obviously the overall response rates. The other is also looking at the symptom burden across patients and looking to reduce kind of the other symptom burden as well as kind of some of the side effect profiles. Patricia, maybe you can expand on that b ack to Mike.
Yeah. Thanks, Mike, for the question. You know, when we talk to the KOLs, they believe that if we can see a response rate anything better than 40%, that would be really a good bar to reach. You know, one of the things that we have noted with selinexor is that we improve on multiple fronts, so spleen volume reduction, symptom improvement in anemia, and potential disease modification with the reduction in bone marrow fibrosis. It's interesting, even though selinexor has a side effect of anemia, we note that with continued use in these myelofibrosis programs that the anemia actually decreases over time. We're hoping that perhaps the combination of Rux plus selinexor may actually decrease some of the anemia. As you said, we're looking forward to the ASCO poster.
Great. Thank you.
Thanks, Mike.
Next question. Next question is from Colleen Kusy with Baird. Please go ahead.
Hi. Good morning. Thanks for taking our questions. In the phase I study for myelofibrosis that you'll have in ASCO, is there anything that we should keep in mind in terms of the patient selection for that trial, especially when comparing to other MF studies?
Yeah. I'll turn to Patricia for that. Patricia?
Yeah. This is phase I. They're naive to JAK1/2 inhibitors. This is just frontline treatment. They are required to have platelet counts of over 100,000. Other than that, they're just the frontline MF patients. Does that answer your question?
Yes, that's helpful. Thank you. Just in terms of how you're thinking about development in the frontline setting versus the second line setting, and kind of how you've decided the patient population for the second line setting. Kind of understand there's, you know, some differences in whether these patients are really Rux refractory or just, you know, JAK experienced. Can you talk about the patient selection for the second line setting, please?
Yeah. Thanks, Colleen. I think we'll turn to Patricia to expand on that.
All right. Thank you. In the XPORT-MF-035 study, which is the second-line study, as you know, 40% of patients respond to frontline treatment with Rux, leaving 60% of patients looking for options. There are no other classes of treatment other than the JAK inhibitors. You know, there's a significant potential to increase responses and improve survival in these patients. With a new class of drugs, we feel like this could really help the patients and give them more options.
I think, Colleen, to add on that, we're truly looking for patients who are kind of rux refractory with at least 24 weeks or six months exposure to a JAK inhibitor.
Okay. Great. Thank you. As a quick follow-on, as you've done more work on p53 wild-type, are there any other tumor types that you think might make sense to pursue based on the signal that you're seeing in endometrial?
Yeah. That's a great, it's a great question. We're continuing to do work on that, obviously with our development team. Maybe do you want to expand on that, Reshma?
Yeah, absolutely. I mean, you know, p53, the exploratory subgroup from the SIENDO trial really did show impressive results. I mean, these are very preliminary, but, you know, impressive results, again, in that exploratory subgroup. We're continuing to look at p53 across multiple tumors, including our hematologic malignancies as well as other solid tumors, and hope to look at, you know, the potential for p53 wild-type a s a potential sub, you know, we can be looking at. You know, we are looking at p53, but really across the board to best identify potential markers that we can pursue across a range of different tumor types and patient populations.
Great. Thanks for taking our question.
Thanks, Colleen.
The next question is from Brian Abrahams with RBC Capital Markets. Please go ahead.
Hi, this is Joe on for Brian. Thanks for taking our question. Can you talk a little bit about the Rux combo study in MF? So for the patient choice arm, can the physicians choose some of the newer JAK inhibitors that are recently approved or that may be approved? How do you see this impacting the potential responses across the arms? For the monotherapy use for selinexor, how do you see the post-Rux landscape evolving and where can selinexor fit in? Thank you.
Sure. Maybe I'll turn to Patricia to talk to those two parts. Patricia?
Yes. The frontline trial in treatment naive is looking at ruxolitinib plus selinexor versus ruxolitinib single agent. In that one, the physicians don't choose the JAK inhibitor. In the other trial, zero three five, which is second line, that one is selinexor versus physician's choice. The physicians can choose to either reuse ruxolitinib or they can choose any of the other treatments that are currently available. Chemotherapy, fedratinib, androgens, interferon, anything that is available for them. You know, as far as the treatment landscape, obviously, there's been a couple of approvals. Pacritinib was approved for patients who have platelet counts less than 50. We know that there was just an acquisition of momelotinib, which is of course another JAK inhibitor. Again, you know, we're pretty excited about selinexor as it gives patients a new mechanism of action outside of the JAK inhibitor population.
I think, Joe, building on that, what's really important is looking for the response rates in those refractory MF and giving, as Patricia just touched on the end, you know, if you can have an efficacious agent which is a different class, starting to really give patients more opportunity for multiple classes, which, we've seen a huge benefit obviously in multiple myeloma over the last decade or so.
All right. That was very helpful. Thank you.
Thanks.
The next question is from Eric Joseph with J.P. Morgan. Please go ahead.
Hi. Good morning. Thanks for taking the questions. Just coming back to the COVID commercial impact, if it makes sense that COVID would impact new starts for the quarter, is it also your sense that this in fact impacted prescription refills as well? I'm just trying to reconcile sort of where the impact was experienced given the steady 50/50 mix between earlier and late line. To what extent, I guess, was there any shift in gross to net given the typical, you know, the coverage gap on the side of payers that we see in first quarter?
Thanks, Eric. I'll turn to Sohanya for that to touch on the refill, and then I can have Mike talk to the shift Q over Q on the GTN.
Thanks, Eric, for the question. Overall, if you compare quarter-over-quarter demand units, we maintain demand units despite COVID impact and the seasonality impact. If we're breaking it down to new starts versus refills, the new starts were impacted, particularly in January and February by COVID. However, we did see a growth in new starts again in March. Overall, COVID did have an impact on new starts because oncology patient visits from the data that we see were impacted negatively by about 10% in January and February. Now, if you take a look at our refills, we actually continue to improve our refill rate since the Boston launch, and the patients are showing signs of staying on therapy longer, particularly in the earlier lines.
as I mentioned before, for example, we see this increasing proportion of patients in four cycles or more. We're making good progress overall despite the COVID impact early this year.
Mike, do you want to touch on the GTN from Q4 to Q1?
Sure. Q1 GTN, as we mentioned in the call, was right around 19% versus Q4 GTN was around 15%. You know, typical higher in Q1 versus in Q4 that, you know, you see every year. We did guide on the call that we, you know, we expect to be somewhere between 15% - 20% for the full year 2022.
Okay. That's very helpful. Maybe just a follow-up question on MM031. I guess as that study gets underway this year, does patient enrollment there present at all a headwind to you know, your commercial guidance for XPOVIO for the full year? On the cost side related to that trial, you know, given the life cycle opportunity for both you and your partners, Antengene and Menarini, I'm wondering to what extent they might be contributing to you know, costs associated with conducting that study. Thanks.
Yes, thanks. Thanks, Eric. No, I think when you look at that study, you know, in combination with Pomalyst, you know, we're running that study in the U.S. and in Europe, and so I don't see it having any impact on our commercial performance. I think moving forward, as we're expecting to see that data, you know, the top line in 2024, working to gain approval, pending the data. In 2025, you know, having the opportunity for an all-oral, and having that opportunity, as you know, the study is having patients to be exposed to anti-CD38 up front.
I think as we see the continued shift with increasing number of patients in the first two lines being treated with an anti-CD38 to be able to really have the combination for an efficacious all-oral I think will drive you know significant value for us and for patients and for our partners as we move forward.
Okay. Thanks for taking the questions.
Thanks, Eric.
The next question is from Edward White with H.C. Wainwright. Please go ahead.
Good morning. Thanks for taking my questions. Can you give us your thoughts on off-label use right now with Pomalyst and the other combinations, you know, the ones that perhaps are in the NCCN guidelines? Then also you had mentioned that virtual versus in-person detailing is improving. In March, I believe you mentioned 60% were in person. Can you just give us some of the historical numbers for that? How low did it go in January and February? What was the comparison to the fourth quarter of last year? Then is there a noticeable difference in accounts that are virtual versus in-person detailing? Are you seeing a bigger penetration in prescriptions? Thank you.
Thanks, Ed. We'll add those three questions together, and we'll get Sohanya to run through them. Sohanya?
Hi, Ed. Thanks for the questions. I'll take that in three parts. First of all, looking at just the mix of regimens and the utilization. Just you know, looking at the data, right? We don't have full visibility into all of the XPOVIO data, and there can be fluctuations quarter over quarter. From what we are seeing since the launch of BOSTON, there is an overall increase in the use of triplets versus the doublets. Now, the triplet use, it's kind of split between XVd and the other regimens. We do see use of other regimens, including XPOVIO combination with pomalidomide, daratumumab, and Kyprolis. Now, all four triplets are on the NCCN guidelines. However, we only promote to the XVd regimen.
It's really physician's discretion on how they and which regimen that they choose based on the prior therapy. Moving to your next question on just live visits versus virtual. To date, we're roughly our live visits are about 60%, in the January, February months, we saw drops to as low as 30%-40%, given the increased restrictions and impact from the surge in COVID. In Q4, we saw roughly in the mid-fifties, even split between virtual versus in person. Overall, I would say outside of the surge in COVID, we're seeing a return to pre-COVID levels in terms of live engagements. As far as effectiveness of live versus virtual, I believe both are equally effective.
It's always great to be in front of a customer live. However, the team has truly adapted. Our resources have adapted digitally, and we have really optimized our virtual channels as well as our live. Both channels end up being quite effective, but our preference as a field team is always to get in front of the customer in person, which is particularly effective in this stage of our launch. We continue to want to see those live engagements improve.
I think we have time for one more question, operator.
The next question is from Jonathan Chang with SVB Securities. Please go ahead.
Hi, guys. This is Scott Schoenhaus for Jonathan. Just wanted to ask, could you describe what the endometrial cancer, the new study design might look like, and sort of how you think about this study relative to others ongoing in the landscape?
Yes, thanks. I think for that, I'll turn it over to Patricia to talk to the potential study design. As you know, we're still engaging with the FDA, so it's still high level. Maybe what we're seeing in the environment overall moving forward, Patricia.
Yeah. Thanks for the question. As Richard said, you know, we've really worked with ENGOT, GOG, and the steering committee to kind of design an appropriate clinical trial. We have a meeting scheduled with the FDA to discuss the study. We know that it's gonna be a randomized placebo-controlled trial, and it will be maintenance therapy for patients with p53 wild-type endometrial cancer who've responded to chemotherapy. Obviously, we'll give more details on the study design when we initiate the study in the second half of this year. As far as the landscape, you know, there's a lot of studies that are ongoing in endometrial cancer, and we're waiting for those to mature and see how they read out.
Got it. Thank you.
This concludes.
With that, I think we're
The question and answer session. Oh, I'm sorry.
Thank you, operator. I'd like to thank everyone for joining today's call, and have a great day, everyone.
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