Karyopharm Therapeutics (KPTI) Q1 2022 Earnings Call Transcript

Karyopharm Therapeutics (KPTI -3.54%)
Q1 2022 Earnings Call
May 05, 2022, 8:30 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good morning, and welcome to the Karyopharm Therapeutics first quarter 2022 earnings conference call. [Operator instructions] 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.

Elhan Webb -- Senior Vice President, Investor Relations

Thank you, operator, and thank you, all, for joining us on today's conference call to discuss the 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. Pat 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 the slide presentation that we will reference during to this call, are available under the Events & Presentation section of our website at karyopharm.com. For today's call, as seen on Slide 2, 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 program. 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 3. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussing 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 claim 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 turn the call over to Richard. Please turn the slide.

Richard Paulson -- President and Chief Executive Officer

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 5, 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 multi 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 multi myeloma franchise to our 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 two to four years. Our third pillar is our people and we strengthened the leadership team during the 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 focus 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 6, 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 3 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 3 study in the second half of this year. We'll be presenting results at the upcoming ASCO 2022 annual meeting, including results from our subgroup and molecular analysis from this SIENDO study and the preliminary from our Phase 1/2 study investigating selinexor combined with ruxolitinib in patients with treatment-naive myelofibrosis. And 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 7. 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 syndrome. 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 8, I would like to turn the call over to Sohanya for her review of the commercial performance for the quarter. Sohanya?

Sohanya Cheng -- Chief Commercial Officer

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 line. Slide 9 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 3 study with selinexor, pomalidomide, and dexamethasone, an all-oral triple 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.

And 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 continue 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 regimen 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 to $145 million. We see strong and consistent momentum across all our growth drivers, increasing confidence among 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' disease 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.

Reshma Rangwala -- Chief Medical Officer

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 enrolled with increasing responsibility at three life science companies, including Aravive, Genmab, and Merck.

During my career in industry, I've 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 I&D filings for Phase 1s 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'm 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 SPO1 inhibition and I am excited to realize that the potential of these therapies for patients that are being evaluated in our four core programs.

Now turning the Slide 12, I will be reviewing our clinical developmental pipeline from our four core programs. As we look to the future on Slide 13, one of our top priorities is to expand our footprints 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 in other Asia-Pacific markets through our strategic partners. Turning now Slide 14 and some updates from our developmental pipeline. I'll start first with multiple myeloma. In addition to the work.

So 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're 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 3 study in the first half of 2022 that is designed to evaluate the SPd triplet regimen in patients with triple 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 a 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.

Pat Judson -- Senior Vice President, Medical Strategy

Thank you, Reshma. So first, I'll provide an overview of the unmet need in endometrial cancer, and why we find our upcoming opportunity 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-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 3 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 the 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 for Gynecologic Oncology Trials or ENGOT to initiate a registration-enabling Phase 3 study, which we plan to initiate during the second half of 2022. I would now like to highlight our rapidly advancing myelofibrosis program in 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 four years.

Once patients stop responding, the expected median survival is approximately 14 months and the five-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 2 ESSENTIAL study, which looked at single-agent selinexor in patients after a JAK inhibitor. 40% of patients in this study achieved a spleen volume reduction of 35%, or greater, following at least 24 weeks of treatment.

The two-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 2g/dL 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 and 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 therapies, 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 2 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 six months of prior treatment with a JAK inhibitor. The primary objective of this study is to assess SVR35 and key secondary endpoints include TSS50, overall response rates, overall survival, anemia response, impacts 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 out to Slide 20.

So this is our frontline myelofibrosis study, a Phase 1/2 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 1 data at the upcoming ASCO 2022 annual meeting.

With that, I'm now going to advance the Slide 21 and turn the call over to Mike to review the first quarter financial highlights. Mike?

Mike Mason -- Chief Financial Officer

Thank you, Patricia. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which began 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 growth to net discount for Xpovio in the first quarter was 19%. We expect growth to net discount to be in the 15% to 20% range for the full year 2022. We recognize $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 was primarily attributable to higher clinical trial expenses, including start-up costs for the Phase 3 SPD study for the first quarter of 2021. Cash, cash equivalents, restricted cash, and investments, as of March 31 22, 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 to $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 to $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 2 study. Therefore, we expect non-GAAP R&D expenses to decrease by approximately 10%, including the cost of the SIENDO 2 trial, compared to 2021 with most of the decreased expected to occur in the second half of 2022. And finally that our existing cash, cash equivalents and investments, as well as the revenue we expect to generate from Xpovio product sales and other licensed revenues, will be sufficient to fund our planned operations into early 2024.

I'll now flip the Slide 23 and turn the call back for Richard.

Richard Paulson -- President and Chief Executive Officer

Thanks, Mike. We believe that we are well-positioned for our strong 2022, both on the commercial front as a 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 to on over the near-term, in addition to our continued focus on driving commercial performance, are to dose the first patient in our Phase 3 study, evaluating the all-oral SPD triplet in patients with relapse or refractory multi myeloma by the end of the first half of 2022; and receive a decision from CHMP on our application requesting approval for selinexor, rituximab 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 '22. We are also planning to initiate a new registration-enabling Phase 3 study in p53 wild-type tumors during the second half of '22. For the myelofibrosis program, we look forward to presenting topline Phase 1 selinexor data in combination with JAK inhibition in treatment-naive myelofibrosis also at ASCO '22. And finally, for the MDS program, we expect to report preliminary Phase 1 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?

Questions & Answers:

Operator

[Operator instructions] The first question comes from Maury Raycroft with Jefferies. Please go ahead.

Maury Raycroft -- Jefferies -- Analyst

Hi, good morning, and thanks for taking my question. 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 are looking for selinexor plus rux for this combo to differentiate from some of the other rux combos in the clinic.

Richard Paulson -- President and Chief Executive Officer

Yeah. Thanks, Maury. For the first part of that, I'll pass it over to Patricia to talk about what we expect to see at ASCO and also what we expect to see in combining rux with selinexor in the frontline myelofibrosis. So, Patricia?

Pat Judson -- Senior Vice President, Medical Strategy

Yeah, thanks. So we're really excited about the preliminary data that we're going to be reporting at ASCO in about a month. So this is going to be the Phase 1 portion of the ongoing Phase 1/2 trial that obviously is looking at selinexor in combination with ruxolitinib in patients with treatment-naive myelofibrosis. So obviously we'll share more details when the ASCO abstracts are released on May 26.

What we're hoping to see with this combination, so 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. So as I reviewed during the presentation, in the ESSENTIAL trial with monotherapy selinexor, we saw really durable spleen responses. 40% of patients achieved SVR35 at 24 weeks or greater. In the ruxolitinib trial, 40% of patients achieved SVR35.

Therefore, the combination should be higher than this.

Maury Raycroft -- Jefferies -- Analyst

Got it. That's really helpful. And also wanted to ask a question about myeloma too. So 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? And can we learn more about that this year over the next couple of quarterly updates?

Richard Paulson -- President and Chief Executive Officer

Yeah. Thanks, Maury. I'll turn for to Sohanya to take you through that.

Sohanya Cheng -- Chief Commercial Officer

Thanks, Maury, for the question. So yes, we continue to see that steady shift into the second to fourth line. And we see now greater than 50% of our patients now in the second to fourth line versus the fifth line plus. And the good news is the patients are seeing the benefit here and are staying on therapy longer.

So we are 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.

Richard Paulson -- President and Chief Executive Officer

And we'll continue to update on that as we move forward, Maury, during the year.

Maury Raycroft -- Jefferies -- Analyst

OK, OK, very good. Thanks for taking my questions.

Richard Paulson -- President and Chief Executive Officer

Thank you.

Operator

The next question is from Peter Lawson with Barclays. Please go ahead.

Peter Lawson -- Barclays -- Analyst

Hey, thanks for taking my questions. Thanks. I guess the first one's just around the impact of COVID. Is there any way, Richard or Mike, to, kind of, break out the impact of COVID in the first couple of months of the quarter?

Richard Paulson -- President and Chief Executive Officer

Yeah. Thanks, Peter. I'll let Sohanya do that because it's pretty clear as you look at some of the numbers. Sohanya?

Sohanya Cheng -- Chief Commercial Officer

Yeah. Thanks, Peter. So overall, when you think about COVID impact, there's a couple of different facets, right? So 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 on new patients starts in that January to February period.

The second component in terms of COVID impact is field activity and access to physicians. And this was impeded in that January to February period, including our proportion of live engagements. And 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 clinics; 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. So we continue to see that positive shift in earlier lines, which gives us that duration benefit. We continue to increase our breadth, but, more importantly, our depth of use of Xpovio.

And we also improved our perception per the intent-to-prescribe data.

Peter Lawson -- Barclays -- Analyst

Thank you. And 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? And what are the factors there and how should we think that kind of playing out through the year?

Richard Paulson -- President and Chief Executive Officer

Yeah. Thank you, Peter. I'll turn that over to Sohanya in a minute, but, as you know, there's obviously those dynamics that happen Q over Q. 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, but I'll turn to Sohanya to kind of take you through why we have the confidence to deliver on that for the full year.

Sohanya Cheng -- Chief Commercial Officer

Great. Thanks, Peter. So, first of all, 30% year-over-year net product revenue growth, I feel extremely good about, 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.

So our focus for the rest of this year is to accelerate that earlier line shift. And we've seen our most rapid growth in the third line, and our focus is to continue to accelerate that third line growth. And as I mentioned earlier, you see, as a result, the benefit on duration when these patients move into earlier lines. I think the second area focuses, we talked about breadth and depth, but as we evolve through our launch phase, our focus becomes accelerating depth.

So 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 a third of the business, we saw almost 50% revenue growth. So for the rest of this year with the access improving to our physicians, driving depth will be a critical success factor. And 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 proving perception of both the efficacy, as well as the safety.

And then in terms of, Richard pointed out, there can be quarter-over-quarter fluctuations. Typically they're in Q4, Q1. You see some seasonality dynamics, some buying pattern dynamics in Q4, but 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. So I feel confident about our annual guidance of $135 million to $145 million.

Peter Lawson -- Barclays -- Analyst

Got you. Are there any clues from the -- either the scripts or of the access or patient flow for April as well? How did that -- did that get better over March? Final question.

Richard Paulson -- President and Chief Executive Officer

Yeah, well, I think we'll comment on that as we get into Q2. I think we just want to focus on Q1 now because it takes a while obviously for that data to mature and see what it looks like.

Peter Lawson -- Barclays -- Analyst

Got you. OK. Thanks so much.

Richard Paulson -- President and Chief Executive Officer

Thanks, Peter.

Operator

The next question is from Mike Ulz with Morgan Stanley. Please go ahead.

Mike Ulz -- Morgan Stanley -- Analyst

Hey, guys. Thanks for taking the question. Just given that you're seeing some impact of COVID on the commercial side, I'm just curious if you're seeing any impact on the enrollment side, specifically for your Phase 2 MF and MDS studies.

Richard Paulson -- President and Chief Executive Officer

Yeah. Thanks, Mike. I'll hit that at a high level and then I'll turn it over to Reshma. But I think as we all experienced in the environment in January and February, a number of staff were out across our clinical trial sites, so that did affect some of our start-ups, did affect some of the access in different areas.

And Reshma, maybe, do you want to expand on that a little bit?

Reshma Rangwala -- Chief Medical Officer

Yeah. We see that -- and 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 at our facilities.

With that said, hopefully we should be seeing a turnaround and continued enrollments, and potentially expanded enrollments, in all of our studies.

Mike Ulz -- Morgan Stanley -- Analyst

Got it. That's helpful. And maybe just one more question for 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 mention 40% is, kind of, what, what to expect for rux and in combination, you should be above that.

But as you think about moving this program forward in the future, what's meaningfully above 40%? Is it 10 percentage points? Is it more than that? Or just -- to provide some of color there, that would be helpful. Thanks.

Richard Paulson -- President and Chief Executive Officer

Yeah. Thanks, Mike. I'll turn to Patricia to talk to that, but I think there's a number of areas that Patricia will talk on. One is obviously the overall response rate.

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. So Patricia, maybe you can expand on that back to Mike?

Pat Judson -- Senior Vice President, Medical Strategy

Yeah. Thanks, Mike, for the question. So when we talk to the KOLs, they believe that if we can see a response rate, anything better than 40%, that that would be a really a good bar to reach. One of the things that we have noted with selinexor is that we improve on multiple fronts.

So spleen volume reduction, symptom improvement, improvement in anemia, and potential disease modification with the reduction in bone marrow fibrosis. And 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. So we're hoping that perhaps the combination of rux plus selinexor may actually decrease some of the anemia. But as you said, we're looking forward to the ASCO poster.

Mike Ulz -- Morgan Stanley -- Analyst

Great. Thank you.

Richard Paulson -- President and Chief Executive Officer

Thanks, Mike.

Operator

The next question is from Colleen Kusy with Baird. Please go ahead.

Colleen Kusy -- Baird -- Analyst

Hi, good morning. Thanks for taking our questions. So in the Phase 1 study for myelofibrosis that you'll have at 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.

Richard Paulson -- President and Chief Executive Officer

Yeah, I'll turn to Patricia for that. Patricia?

Pat Judson -- Senior Vice President, Medical Strategy

Yeah. So this is -- Phase 1, they're naive to JAK 1/2 inhibitors. So this is just frontline treatment. They are required to have platelet counts of over 100,000.

And other than that, they're just the frontline MF patients. Does that answer your question?

Colleen Kusy -- Baird -- Analyst

Yes, that's helpful. Thank you. And then 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 treatment -- the patient population for the second-line setting, kind of, understand there's some differences in whether these patients are really rux refractory, or just JAK experience. So if you talk about the patient selection for the second-line setting, please.

Richard Paulson -- President and Chief Executive Officer

Yeah. Thanks, Colleen. We'll turn to Patricia to expand on that.

Pat Judson -- Senior Vice President, Medical Strategy

All right. Thank you. So in the 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.

And so there's a significant potential increased responses and improved survival in these patients. With a new class of drugs, we feel like this could really help the patients and give them more options.

Richard Paulson -- President and Chief Executive Officer

And 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.

Colleen Kusy -- Baird -- Analyst

OK, great. Thank you. And 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?

Richard Paulson -- President and Chief Executive Officer

Yeah. That's a great question. We're continuing to do work on that obviously with our development team. And maybe, do you want to expand on that, Reshma?

Reshma Rangwala -- Chief Medical Officer

Yeah, absolutely. I mean, p53, the exploratory subgroup from the SIENDO trial really did show impressive results. I mean, these are very preliminary, but 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 the potential for p53 wild type as a potential sub -- we can be looking at. So 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.

Colleen Kusy -- Baird -- Analyst

Great. Thanks for taking our questions.

Richard Paulson -- President and Chief Executive Officer

Thanks, Colleen.

Operator

The next question is from Brian Abrahams with RBC Capital Markets. Please go ahead.

Unknown speaker -- RBC Capital Markets -- Analyst

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? And for the monotherapy use for selinexor, how do you see the post-rux landscape evolving and where can seli fit in? Thank you.

Richard Paulson -- President and Chief Executive Officer

Sure. Maybe I'll turn to Patricia to talk to those two parts. Patricia?

Pat Judson -- Senior Vice President, Medical Strategy

Yes. So the frontline trial and treatment naive is looking at ruxolitinib plus Selinexor versus ruxolitinib single agent. So in that one, the physicians don't choose the JAK inhibitor. in the other trial 035, which is second line, that one is selinexor versus physician's choice, and the physicians can choose to either reuse ruxolitinib or they can choose any of the other treatments that are currently available.

So chemotherapy, fedratinib, androgens, interferon, anything that is available for them. And then 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 momolitinib, which is, of course, another JAK inhibitor. Again, we're pretty excited about selinexor as it gives patients a new mechanism of action outside of the JAK inhibitor population.

Richard Paulson -- President and Chief Executive Officer

And I think, Joe, building on that what's really important is looking for the response rates and those refractory MF and giving -- as Patricia just touched on the end, if you can have an effication 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.

Unknown speaker -- RBC Capital Markets -- Analyst

All right. That was very helpful. Thank you.

Richard Paulson -- President and Chief Executive Officer

Thanks.

Operator

The next question is from Eric Joseph with J.P. Morgan. Please go ahead.

Eric Joseph -- J.P. Morgan -- Analyst

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 headwind impacted prescription refills as well? I'm just trying to reconcile, sort of, where the impact was experienced, given the sort of the steady 50:50 mix between earlier and late line.

And to what extent, I guess, was there any shift in gross to net, given the cyclical coverage gap on the side of payers that we see in first quarter?

Richard Paulson -- President and Chief Executive Officer

Yeah. 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.

Sohanya Cheng -- Chief Commercial Officer

Thanks, Eric, for the question. So overall, if you compare quarter-over-quarter demand units, we maintain demand units despite COVID impact and the seasonality impact. So if we're breaking it down to new starts versus refills, the new starts were impacted particularly in January and February by COVID, in January and February. However, we did see a growth in new starts again in March.

But 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 have actually continued 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. And as I mentioned before, for example, we see this increasing proportion of patients in four cycles or more. So we're making good progress overall, despite the COVID impact early this year.

Richard Paulson -- President and Chief Executive Officer

And, Mike, do you want to touch on the GTN from Q4 to Q1?

Mike Mason -- Chief Financial Officer

Sure. Q1 GTN, as we mentioned on the call, was right around 19% versus Q4 GTN was around 15%. So, typical higher in Q1 versus in Q4 that you see every year. And we did guide in the call that we expect to be somewhere between 15%and 20% for the full year 2022.

Eric Joseph -- J.P. Morgan -- Analyst

OK, OK. That's very helpful. And maybe just a follow-up question on MM-031. I guess, as that study gets the way this year, does that -- does patient enrollment there present all a headwind to your commercial guidance for exposure for the full year? And then on the cost side related to that trial, given the lifecycle opportunity for both you and your partners, Antengene and Menarini, I'm wondering to what extent they might be contributing to cost associated with conducting that study.

Thanks.

Richard Paulson -- President and Chief Executive Officer

Yes, no. Thanks, Eric. No, I think when you look at that study in combination with [Inaudible], we're running that study in the U.S. and in Europe.

And d so I don't see it having any impact on our commercial performance. And then I think moving forward, as we're expecting to see that data, the top line in 2024, working to gain approval of pending the data in '25, having the opportunity for an all-oral and having that opportunity -- as you know, the study is having patients having to be exposed to anti-CD38 upfront. So I think as we see the continued shift with increasing number of patients in the first two lines being treated with anti-CD38 to be able to really have the combination for an efficacious all-oral, I think will drive significant value for us and for patients, and for our partners, as we move forward.

Eric Joseph -- J.P. Morgan -- Analyst

OK. Thanks for taking the questions.

Richard Paulson -- President and Chief Executive Officer

Thanks, Eric.

Operator

The next question is from Ed White with H.C. Wainwright. Please go ahead.

Ed White -- H.C. Wainwright -- Analyst

Good morning. Thanks for taking my questions. Can you give us your thoughts on off-label use right now with [Inaudible] and the other combinations, the ones that perhaps are in the NCCN guidelines? And 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, and what was the comparison to the fourth quarter of last year? And then, is there a noticeable difference in accounts that are virtual versus in detailing? Are you seeing a bigger penetration in prescriptions? Thank you.

Richard Paulson -- President and Chief Executive Officer

Thanks, Ed. We'll add those three questions together, and we'll get Sohanya to run through them. Sohanya?

Sohanya Cheng -- Chief Commercial Officer

Hi, Ed. Thanks for the questions. I'll take them in three parts. So, first of all, looking at just the mix of regimens and the utilization.

So just looking at the data, right, we don't have full visibility into all of Xpovio data, and there can be fluctuation quarter over quarter, but 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 in combination with pomalidomide, daratumumab, and KYPROLIS. Now all four triplets are on the NCCN guidelines.

However, we only promote to the XVd regimen. And it's really a 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. So to date, where roughly our live visits are about 60%, in the January, February months we saw drops to as low as 30% to 40%, given the increased restrictions and impact from the surge in COVID.

In Q4, we saw roughly in the mid-50s even split between virtual versus in person. So overall, I would say outside of the surge in COVID, we're seeing a return to pre-COVID levels in terms of live engagement. As far as effectiveness of live versus virtual, I think both -- 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 adapt it digitally. And we have really optimized our virtual channels, as well as our lives. So 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. So we continue to want to see those live engagements improve.

Richard Paulson -- President and Chief Executive Officer

And we have time for one more question, operator.

Operator

The next question is from Jonathan Chang with SVB Securities. Please go ahead.

Faisal Khurshid -- SVB Leerink -- Analyst

Hi, guys. This is Faisal on for Jonathan. I 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?

Richard Paulson -- President and Chief Executive Officer

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.

And then maybe what we're seeing in the environment overall, moving forward, Patricia?

Pat Judson -- Senior Vice President, Medical Strategy

Yeah. Thanks for the question. So, as Richard said, 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 going to be a randomized placebo-controlled trial and it'll 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. And then as far as the landscape, 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.

Faisal Khurshid -- SVB Leerink -- Analyst

Got it. Thank you.

Operator

This concludes the question-and-answer session -- I'm sorry.

Richard Paulson -- President and Chief Executive Officer

Thank you, operator. I'd like to thank everyone for joining today's call, and have a great day, everyone.

Operator

[Operator signoff]

Duration: 63 minutes

Call participants:

Elhan Webb -- Senior Vice President, Investor Relations

Richard Paulson -- President and Chief Executive Officer

Sohanya Cheng -- Chief Commercial Officer

Reshma Rangwala -- Chief Medical Officer

Pat Judson -- Senior Vice President, Medical Strategy

Mike Mason -- Chief Financial Officer

Maury Raycroft -- Jefferies -- Analyst

Peter Lawson -- Barclays -- Analyst

Mike Ulz -- Morgan Stanley -- Analyst

Colleen Kusy -- Baird -- Analyst

Unknown speaker -- RBC Capital Markets -- Analyst

Eric Joseph -- J.P. Morgan -- Analyst

Ed White -- H.C. Wainwright -- Analyst

Faisal Khurshid -- SVB Leerink -- Analyst

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