Karyopharm Therapeutics inc (KPTI) Q2 2021 Earnings Call Transcript

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Karyopharm Therapeutics inc (KPTI)
Q2 2021 Earnings Call
Aug 5, 2021, 8:30 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good morning. My name is Karen, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Second Quarter 2021 Financial Results Conference Call. [Operator Instructions] Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Joe Rayne from Argot Partners. Please go ahead, sir.

Joseph Rayne -- Vice President

Thank you, Karen, and thank you all for joining us on today's conference call to discuss Karyopharm's Second Quarter Financial Results and Business Update. Today, I'm joined by Mr. Richard Paulson, President and Chief Executive Officer; Ms. Sohanya Cheng, Senior Vice President, Sales and Commercial Operations; Dr. Jatin Shah, Chief Medical Officer; Mr. Mike Mason Chief Financial Officer; Dr. Sharon Shacham, Chief Scientific Officer; and Mr. Stephen Mitchener, Chief Business Officer. Operator? Okay. I'll continue. During today's call, which is outlined on slide two, Richard will provide some introductory remarks, Sohanya will provide an update on our NEXPOVIO commercial progress, Jatin will highlight recent pipeline advancements and then Mike will discuss the second quarter financial results highlights. We will conclude with some thoughts from Richard on upcoming milestones, and then we'll move to the Q&A portion of the call. Earlier this morning, we issued a press release detailing Karyopharm's results for the second quarter of 2021. This release, along with the slide presentation that we plan to reference on today's call are available on our website at karyopharm.com.

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. These include statements about our future expectations, clinical developments and regulatory matters and time lines, the potential success of our products and product candidates, including our expectations relating to the commercialization of XPOVIO and NEXPOVIO, financial projections and our plans and prospects. 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. I will now turn the call over to Richard Paulson. Please turn to slide four.

Richard Paulson -- President and Chief Executive Officer

Thank you, Joe, and good morning, everyone. Please turn to slide five. Since joining as President and CEO in May, my focus has been on execution to ensure we are providing the highest quality customer engagement and are operating effectively to achieve our milestones. Karyopharm was found on the innovative science of selective inhibition of nuclear export as a mechanism to treat a broad range of cancers with significant unmet need. Our foundation in oncology was established with the regulatory approvals and commercial launches of XPOVIO in three hematological oncology indications. We are proud of the commercial program seen thus far, but no, we still have work to do in order to best serve our patients and drive continued steady growth. Specifically, in multiple myeloma, I believe we have a great opportunity to continue expanding our breadth and depth of XPOVIO through our execution in the approved indications and advancing our late-stage combination studies, which Jatin will cover later in the call. While in parallel, we will continue to build our foundation globally with the completion of the European Medicine Agency's Committee for medicinal products for human use review of our application for NEXPOVIO as a second-line plus treatment for multiple myoma expected in the first half of 2022.

As we look to our greater pipeline, we are actively working to prioritize our clinical development plan in hematological malignancies and in solid tumor indications to focus our efforts on programs with the highest unmet need, probability of success and attractive market opportunities. This includes our Phase III SIENDO study evaluating XPOVIO in endometrial cancer, where there are no approved treatments for maintenance therapy following chemotherapy in any line of treatment. Top line results for this study are expected by the end of this year, and if positive, further reinforces the therapeutic potential of XPOVIO in solid tumor indications. We are also advancing several targeted late-stage clinical studies across multiple solid tumor indications with high unmet needs that Jatin will review later on our call. To support our focused growth plan, we are well capitalized to fund our operations with a cash runway into the middle of 2023. I believe the important efforts we are undertaking today are further building on our foundation and position us well for continued growth. We are actively completing a full strategic review of our pipeline to fine-tune our future objectives and priorities as part of revolution. And we look forward to hosting an Investor Day during the fourth quarter to outline our strategy and pipeline focus to lead Karyopharm through the near-term multiple myeloma growth opportunity and the next chapter of expanding approvals in both solid tumors and additional hematological malignancies.

As we turn now to slide six, I would like to take this opportunity to introduce Sohanya Cheng, our new Senior Vice President of Sales and Commercial Operations. Sohanya brings nearly two decades of biopharmaceutical commercialization and research experience, predominantly in the oncology space. Sohanya spent over 10 years of her career in the commercial organization at Amgen, where she held various sales and marketing leadership roles supporting the commercialization of key oncology brands. Including serving as Executive Director and Head of Marketing and Sales for multiple myeloma and overseeing Kyprolis. We are extremely excited to have Sohanya join the team at this critical time as XPOVIO is rapidly evolving into a standard of care in myeloma. I will now turn the call over to her to review the commercial results for the quarter. Sohanya?

Sohanya Cheng -- Senior Vice President of Sales and Commercial Operations

Thank you, Richard, and good morning, everyone. I share Richard's excitement regarding the potential of XPOVIO in multiple myeloma. I know firsthand about the intricacies of commercializing a product in the multiple myeloma market and firmly believe that XPOVIO provides a differentiated approach to treating this disease. Please now turn to slide seven. Total XPOVIO net product sales for the quarter were $20.2 million, an 8% increase compared to the second quarter of 2020. Year-to-date sales for the first half 2021 were up 21% compared to the first half of 2020. Several key indicators continue to show progress including growth in prescription demand quarter-over-quarter and over 7,600 prescriptions filled as of the end of the second quarter. XPOVIO unit demand was up 28% compared to the second quarter of 2020, up year-to-date 33% compared to the first half of 2020 and up 4% from the first quarter of 2021. According to our market research data, we see a rising confidence in treating physicians overall perception of the XPOVIO product profile across lines at an evolution from penta-refractory to early lines with strong growth in the third line. This is a result of our strong field execution and our proactive education plan that we believe is helping prescribers gain confidence in improving the patient experience with dose reduction and proactive side effect management. We're also reaching more customers and seeing the number of prescribing accounts continue to sequentially increase quarter-over-quarter with 11% growth compared to the first quarter of this year. Patients continue to average at 2.9 treatment cycles of XPOVIO consistent with the previous quarter.

We're still early in the rollout of XPOVIO in the second line plus setting and expect the average duration of treatment to increase over time as more and more patients are treated in earlier lines with a once-weekly XPOVIO dose and as part of a combination triplet regimen. Importantly, approximately 97% of U.S. lives have confirmed access to XPOVIO if prescribed. In June, we launched three new strength tablets for XPOVIO at 40, 50 and 60 milligrams to help healthcare providers individualize the dosing and administration of XPOVIO based on patient needs. These tablet options may also increase patient compliance by simplifying their treatment regimen and reducing the pill burden experienced by some patients. Please now turn to slide eight. Overall, the quarter showed promising growth across several indicators, and we continue to believe there is more work to be done to further increase our position in the market and better expand the reach of XPOVIO. We have recently implemented key initiatives designed to achieve just that. We have delayered and strengthened our commercial team with key additions in marketing and the creation of a launch excellence capability to enhance our execution. Our team is investing in transforming our data capabilities and partnerships with our customers to help identify the right patient for XPOVIO at the right time. Our positioning has adapted to meet a critical unmet need in the treatment paradigm in second line plus. Most patients get treated with IMiDs, PIs and anti-CD38 in the first and second line.

Several different options are approved in the fourth line plus, but there is a white space in the middle section of the treatment journey between the second and the fourth line. We're using a different mechanistic approach also known as a class switch, could be vital for the success of the patient's outcomes. XPOVIO is the first new class of multiple myeloma treatment approved in five years with the ability to combine with different regimens as recognized per the NCCN guidelines. As we look at the myeloma marketplace as a whole, two themes emerge: firstly, the innovation in this space is outstanding and is resulting in patients living longer lives and allowing the market to grow long term; secondly, given the competitive nature in this space, several new entrants from the past few years have shown steady uptake that sustained over 6-plus years. With the foundation we are laying now and with a rapidly advancing myeloma pipeline, we believe we will continue to drive a steady growth in the near, medium and long term. If you will advance to slide nine, I will now turn the call to Jatin to highlight our clinical development efforts to further build our position in multiple myeloma and emerging solid tumor portfolio. Jatin?

Jatin Shah -- Executive Vice President, Chief Medical Officer

Thanks, Sohanya. I'd first like to touch on our exciting pipeline updates and key regulatory advancements. We're making progress on bringing XPOVIO to patients in need across the globe with the recent approvals in the United Kingdom and South Korea that are further outlined in slide 10. Turning now to slide 11. Our priority Phase III study is the SIENDO study, evaluating XPOVIO in patients with endometrial cancer in the maintenance setting. SIENDO is enrolling approximately 248 patients, randomized 2:1 to receive either 80 milligrams of XPOVIO, once weekly or placebo. Eligible patients include those with Stage IV or recurrent disease who have completed the course of taxane-platinum combination chemotherapy and achieved either a partial or complete response. The primary endpoint of the trial is an improvement in progression-free survival, or PFS, as defined as time from randomization until death or disease progression. In November of 2020, we announced a trial that passed its planned interim futility analysis, and so the study continues as planned, and we expect the top line data by the end of this year. We remain highly encouraged by the study and the opportunity for XPOVIO in this disease area as a maintenance therapy, which is outlined on slide 12. Endometrial cancer is the most common gynecologic cancer in the U.S. with over 65,000 new cases. Now while most women are diagnosed with early stage disease and have a good prognosis after surgery alone, approximately 14,000 patients each year and the front line will have advanced or metastatic disease and are treated with chemotherapy.

When their disease progresses, these patients are typically treated with additional chemotherapy immunotherapy and/or targeted agents. However, clearly, there are no approved drugs in the maintenance setting for patients who have a response to chemotherapy in any setting. This is a setting in which we're studying XPOVIO in the SIENDO study. A similar approach was taken with the PARP inhibitors for patients with ovarian cancer and their use in the maintenance setting in that disease is now the standard of care and widely adopted. To put our potential opportunity in endometrial cancer in perspective, assuming about 2/3 of frontline patients respond to chemotherapy, approximately 4,000 patients could be treated each year in the maintenance setting. We look forward to presenting these results later this year, which has the potential to benefit additional patients and has a significant opportunity to expand confidence in XPOVIO's ability to work in both solid and hematologic tumors. Turning now to slide 13. I'd like to review some of the key data presentations from this year's ASCO and EHA annual meetings. First up is the data from the STORM study, which analyzed XPOVIO containing regimens in patients who have previously been treated with an anti-CD38 monoclinical antibody. This is an important setting to explore because at least 70% of patients will be treated with an IMiD, PI and a CD38 in the first two treatment lines. Beyond that, there's a lack of data to guide positions on what will be the next best treatment.

As you can see on slide 14, we have observed strong response rates for the XPOVIO contained triplet combinations XPd and XKd of 58% and 67%, respectively, along with the prolonged PFS with both XPd and XKd. On slide 15, we look specifically at the response rates for XPd, where we see that the response rate at the recommended Phase II dose of 65% and patients who had previously been treated with an anti-CD38 monoclonal antibody had an overall response rate of 58%. Both of these response rates compare favorably to less than the 30% response rate expected for Pomalyst and dexamethasone alone. Advancing now to slide 16, we also present the updated data from all patients in the XPd arm of the STORM study, which continues to show high response rates and the favorable PFS and duration of response. Collectively, these data support the new randomized Phase III study, we expect to initiate by the end of this year. This new study is designed to evaluate XPOVIO in combination with Pomalyst and dexamethasone versus elotuzumab, pomalidomide and dexamethasone in patients who have previously treated myeloma. If the results of these trial are positive, this regimen could represent a prudent, all-oral drug option for patients with early relapsed myeloma. The safety profile continues to be manageable with supportive care and dose modifications. Next, on slide 17, we look specifically at the response rates for XPd, which appears to be highly active in the post-anti-CD38 study. Here, we see response rates ranging from 73% to 87% for these various subgroups, including patients in first relapse in patients with high-risk cytogenetics. Then on slide 18, we show the equally impressive PFS data. PFS for all patients, patients with high-risk cytogenetics and patients who receive an anti-CD38 with 15 months, 15 months and 23.7 months, respectively. On slide 19, we show data presented from all patients in the XKd arm of the STORM study which continue to show high response rates and favorable PFS with no new safety signals identified. Next, on slide 20. We have an overview of some of the important data to come out of the Phase III BOSTON study in patients with multiple myeloma following at least one prior line of therapy. This analysis looked at older patients who are 65 years of age and older. In this group, XPOVIO is associated with a significant overall survival benefit. In addition to the prolonged PFS, better response rates and lower rates of peripheral neuropathy versus the comparator arm. On slide 21, we show the recommended support of care, which is very simple and only requires two antiemetics, which can be tapered and no other prophylactic medications.

On slide 22, we show that the incidence of patients experiencing nausea decreased after the first month of treatment with appropriate dose reduction and anti measures. These results are consistent with the physician feedback that we've experienced for a continued gain and confidence in prescribing XPOVIO. Moving on to slide 23. We are encouraged by the new eltanexor data at ASCO in patients hypomethylating agent refractory myelodysplastic syndrome, an indication with no approved therapies. In this study, single-agent eltanexor achieved an overall response rate of 53% and a median overall survival of 9.9 months with the expected overall survival is three to four months, providing strong rationale for continued development for this attractive market opportunity and unmet medical need. Turning now to slide 24. You can see a snapshot of our robust clinical pipeline, including two new clinical studies that were recently initiated in melanoma and myelofibrosis. As Richard mentioned, we are actively prioritizing our pipeline and focusing our development efforts within hematologic malignancies and solid tumors. This includes building on our breadth and depth in multiple myeloma with the emerging clinical data that continues to show the potential of XPOVIO in combination with other anticancer therapies, and expanding into other hematologic malignancies such as myelofibrosis and MDS with eltanexor. We are also working to demonstrate activity and safety in other high unmet need solid tumor indications in the years ahead, such as endometrial cancer in the SIENDO study. With that, now I'll advance to slide 25 and turn the call over to Mike Mason to review the quarterly financials. Mike?

Michael Mason -- Chief Financial Officer

Thank you, Jatin. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on slide 26. Net product revenue for the second quarter of 2021 was $20.2 million compared to $18.6 million for the second quarter of 2020. Following the launch of our additional strength tablets in June, we saw an approximate $2 million reduction and channel inventory to allow for purchasing of the new tablet sizes, which we expect to be a onetime occurrence. The estimated gross net discount for XPOVIO in the second quarter was 21%, which was slightly higher than our expected range of 15% to 20%, but we continue to expect to be in the 15% to 20% range for the full year of 2021. License and other revenue for the second quarter of 2021 was $2.4 million compared to $14.9 million for the second quarter of 2020. This difference between periods is driven by increased recognition of revenue from our license agreement with Antengene and Ono Pharmaceuticals in 2020. We expect to recognize $10 million in the third quarter of 2021 for achieving two regulatory milestones from our Antengene collaboration. R&D expenses for the second quarter of 2021 were $34 million, compared to $42.6 million in the second quarter of 2020.

The decrease in R&D expenses in the second quarter of 2021 compared to the second quarter of 2020 was primarily attributable to the COVID-19 trial activity in the second quarter of 2020 that did not occur in 2021. SG&A expenses for the second quarter of 2021 were $36.5 million, compared to $30.8 million for the second quarter of 2020. The increase in SG&A expenses compared to the second quarter of 2020 was due primarily to activities to support the U.S. commercialization of XPOVIO, including the launch of XPOVIO in the second line plus setting. Cash, cash equivalents, restricted cash and investments as of June 30, 2021 totaled $239.3 million compared to $276.7 million as of December 31, 2020. On slide 27, you can see that based on our current operating plans, we expect our non-GAAP R&D and SG&A expenses, which excludes stock-based compensation expense, for the full year 2021, to be in the range of $270 million to $290 million. We expect that our existing cash, 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 the middle of 2023. I'll now flip to slide 28 and turn the call over to Richard for some final thoughts. Richard?

Richard Paulson -- President and Chief Executive Officer

Thank you, Mike. We've already made strong steps forward in the first half of the year, including the expansion of XPOVIO in the second line plus treatment setting, the enhancement of our commercial capabilities from our future growth, securing an additional $60 million in funding from healthcare royalty, the conditional marketing approval in Europe and the U.K. and numerous other clinical development advances. As we look ahead, we are focused on execution to drive our evolution and have several key milestones to look forward as listed on slide 29. In multiple myeloma, our focus is on the continued enhancement and effectiveness of our commercial organization to promote increased XPOVIO sales in the second line plus treatment setting. We plan to initiate our Phase III study of XPd in multiple myeloma later this year, an oral combination that could allow us to further build in the multiple myeloma landscape. From our solid tumor programs, we expect top line data from the Phase III SIENDO study in endometrial cancer later this year, a market opportunity where there are no approved drugs in the maintenance setting following chemotherapy in any line of treatment. We also plan to initiate multiple late-stage clinical studies in myelodysplastic syndromes, myelofibrosis and colorectal cancer. We expect to present combination data from both our hematological malignancies and solid tumor programs at medical meetings in the coming months, including at ESMO in September. Lastly, we plan to hold an Investor Day during the fourth quarter to review our strategic imperatives and pipeline priorities to support our evolution and the company. To close, I would like to recognize and thank our employees for their hard work thus far this year and dedication to serving our patients. I look forward to updating the investment community on our continued progress in the months and quarters ahead. And with that, I would now like to ask the operator to open up the call to question-and-answer portion of today's presentation. Operator?

Questions and Answers:

Operator

The board is now open for questions [Operator Instructions] We'll take our first question from Maury Raycroft with Jefferies. Please go ahead.

Unidentified Participant

Good morning. This is Kevin Strang in for Maury, Thank you for taking my questions. So just wanted to ask if you could potentially book and what your average prescription renewal numbers could look like. They are in terms of..increase in treatment duration versus increase in new providers or new patient startts?

Richard Paulson -- President and Chief Executive Officer

Sure, Kevin, yeah. Let me turn to Sohanya to expand on that. Sohanya?

Sohanya Cheng -- Senior Vice President of Sales and Commercial Operations

Yes. Great. Kevin, thank you for the question. So first, I just like to kind of underscore the demand growth that we've seen in the first six months of our launch in the second line, again, 28%, year-over-year for the quarter and 33% for the first half of this year versus last year and feel very good about this growth. Regarding some of the drivers that you mentioned around new patient starts and prescriber base, we're seeing very positive growth on new patients starts, as well as on expanding our user customer base as we're adding new accounts quarter-over-quarter. Furthermore, we're also seeing a gain in confidence based on our intent to prescribe data of physicians and their overall perception of the product.

Unidentified Participant

Great, Thank you. And then just another question on the rationale and strategy for Eltanexor and MDS, maybe a single agent and then combo. And then also same question for Myelofibrosis and maybe what your expected positioning is in these indications?

Richard Paulson -- President and Chief Executive Officer

Sure, Kevin. Let me turn to Jatin to talk to those two. Jatin?

Jatin Shah -- Executive Vice President, Chief Medical Officer

Yes, absolutely. Thanks so much. So I think the rationale for exploring Eltanexor and MDS is really based on two things. One is strong pre-clinical rationale. We have early data from selinexor and MDS and now additional data with Eltanexor and MDS as well. And keep in mind two things. One, there's no approved indication -- no approved therapies in the relapsed MDS space. And other therapies, including [Indecipherable], which are effective drugs, have a response rate of less than 10% in relapsed MDS, especially primary refractory MDS.

So in that setting that we're looking at the overall response rate of 53% with Eltanexor as a single agent, the overall survival greater than nine months or an expected survival of three to four months. So it's in that setting that we see a strong rationale to develop Eltanexor in the single agent in refractory MDS as well as looking at combinations in the future and earlier lines of therapy. Similar thoughts...

Richard Paulson -- President and Chief Executive Officer

Hey, Jatin. If you can just talk to Myelofibrosis as well?

Jatin Shah -- Executive Vice President, Chief Medical Officer

Yes. That's actually the same thought in Myelofibrosis. There's really outside of JAK inhibitors limited therapeutic options for patients in the relapsed Myelofibrosis space. There's a now new JAK inhibitor in that space, but really the same class of drugs. And so you'll see data coming out of ASH again, the strong preclinical rationale, and you'll see data coming out of ASH, where we see in an IST single agent activity with selinexor, given once weekly at a low dose in myelofibrosis, and is based on that we're moving forward with the studies that were planned. And we're also exploring a combination with [Indecipherable] in the newly diagnosed setting. Again, keeping in mind that there's limited therapeutic options for patients with Myelofibrosis and only one class of drugs right now that are approved and Myelofibrosis JAK inhibitors we're seeing some single agent activity that's promising.

Unidentified Participant

Great, Thank you very much.

Operator

We'll take our next question from Brian Abrams with RBC Capital Markets. Please go ahead.

Brian Corey Abrahams -- RBC Capital -- Analyst

Hey, guys, Thank you so much for taking my questions. Good morning. A few for me. As first off, I was hoping to reconcile some of the metrics that you provided a little bit more. So sounds like prescription demand is steady. Gross to net was flat quarter-over-quarter and you took a 5% or so price increase at the beginning of the quarter. So I guess I'm wondering why that's not pulling through to sales numbers more. Is this all just because of that in negative inventory effect? Are you seeing any, I guess, extended spacing of doses for patients who might be titrating down? And I guess to that end, why do you think gross to net wasn't more improved quarter-over-quarter? And do you think the new strengths that you're launching could potentially mitigate some of that individualized lower frequency spacing of prescriptions, or spacing of doses?

Richard Paulson -- President and Chief Executive Officer

Thanks, Brian had a few questions in there. So maybe I'll start Mike to talk on, the GTN and the impact of inventory. And then, we'll turn to Sohanya to talk about the metrics with regards to demand, Mike?

Michael Mason -- Chief Financial Officer

Sure. Hi. Brian. Yeah, so just to help with the reconciliation with the rollout of the alternate size, the three new alternate size tablets, as Sohanya mentioned earlier in the call. We did see our customers are in specialty pharmacies and especially distributors sort of reset their channel. We do expect it to be a bit of a one-time occurrence. So the focus really is on demand, which is up about 4% quarter on -- yeah Q1 to Q2. And with that, when they switching over to growth set, I'll go back to Sohanya who is facing. So growth was 21% for the quarter, like we said slightly higher than the range of 15% and 20%. But you're right. It is also a reset on pricing something like 3b to 4b etc., so we do expect that to come down and Q3 and Q4. And we'll be well within a range of 15% to 20% for the year.

Sohanya Cheng -- Senior Vice President of Sales and Commercial Operations

Great, thanks. So let me touch on some of the demand drivers and specifically your question around duration. Again, going back to the demand growth that we saw in the first half of the year is 33%, in the first half of this year, versus the first half of last year. So very good demand growth here. Some of the drivers I touched on earlier. New patient stuff starts, prescriber base, increasing. We are gaining of confidence, and then the movement toward earlier lines. Now let me touch on duration of therapy and the tight earlier lines. When we think about duration of therapy, you got to look at the reasons for discontinuation of treatment. There's two, primary drivers of that, first, side effect management and second, disease progression. Now as we progress and shift from later line to earlier lines, which is a primary focus of our strategy and execution. And as we proactively educate on side effect management, we will see progress here as a duration of therapy. Again, we're still early in the rollout of the second line plus launch, and it takes time for the real world data to mature.

Brian Corey Abrahams -- RBC Capital -- Analyst

Got it? And then, can you speak a little bit more to your outlook for XPOVIO in the back half of this year? Are you seeing improvements in duration, refill rates, demand exiting the quarter in June, July versus earlier in the year? And I guess, how -- I guess what should we be looking for as we get into the back half of this year in terms of expected growth? I know a lot of the pull through takes time for you as you move to earlier lines. Is this something that you'd expect to inflect this year or in the other years? Thanks.

Richard Paulson -- President and Chief Executive Officer

Thanks, Brian, let me start with that. And then, I'll turn it to Sohanya. We are seeing, as we said, really good progress and moving up into earlier lines of treatment. And then, it's a difficult area to measure, there's only qualitative market research, not quantitative data on that with regards to the lines of therapy. But I do think one of the key indicators is really looking at how patients are being prescribed either the 160, starting dose or the 100 starting dose. So last year, in the first half of the year, about 50% of patients were getting the 160 starting dose, whereas this year, now, in the first half of the year, only about 15%, one, five, are getting that 160, so about 85% that are getting the 100, or the 80 kind of starting dose. So I think that's a real good leading indicator of how we're moving forward into the triplets and how we're moving forward into earlier lines of therapy. And maybe I'll turn to Sohanya to talk about some of our qualitative research, which helps to strengthen that and is a leading indicator going into the rest of the year.

Sohanya Cheng -- Senior Vice President of Sales and Commercial Operations

Thanks, Richard. Yes, as I mentioned earlier, and intent to prescribe data, we see a couple of things. One is that increasing confidence among the vision in the overall perception of the product. And this is a key leading indicator, because the perception on both the efficacy and tolerability profile of the product is improving. Also, on the intent to prescribe data, we see a shift from the leader lines to the earlier line. So, I feel very good about the momentum that we've seen in the first half of the year. I am also very excited by the team that we have in place, which is excited, passionate, and highly patient-focused. We are 100% focused on execution and growth in the second half of this year. We've initiated a couple of key initiatives in enhancing our commercial and data capabilities that I touched on earlier delayering the sales and marketing team, reporting directly to Richard. We've identified new data partnerships to get to the right patient at the right time. We're enhancing our digital capabilities to better target our customers. So, lots of good initiatives in place. And I'm confident about the growth that will continue not just through the end of this year, but that will sustain in the medium and long-term as well.

Brian Corey Abrahams -- RBC Capital -- Analyst

Great. Thanks so much. I'll hop back in the queue.

Operator

Our next question comes from Peter Lawson with Barclays. Please go ahead, sir.

Peter Richard Lawson -- Barclays Bank -- Analyst

Great, thank you. Thanks for taking the questions. Just as we think about the dynamics, whether -- did you see headwinds or impact from COVID or your sense around trends in oncology visits, and if that kind of impacted underlying growth?

Richard Paulson -- President and Chief Executive Officer

Yes, thanks Peter. I think as we hear from everybody, and we all experience every day, we continue to work through the challenges of COVID. But I'll turn to Sohanya to go through some more of the specifics on it. Sohanya?

Sohanya Cheng -- Senior Vice President of Sales and Commercial Operations

Great. Thank you, Peter for the question. So, we continue to see recovery from the impacts of COVID, both on patient visits, as well as field activity, but we have not reached to the pre-COVID level baseline. So, to kind of double click on the US field activity, we've improved quarter-over-quarter reaching 90% of pre-COVID levels, and our face-to-face customer interactions are increasing and are about 60% of the activity during the second quarter. The education happening both in-person and virtually, we've really optimized and it is having an impact, as I spoke to earlier, in the -- in how we're moving the needle on some of the intent to prescribe data. So, we are seeing good momentum. We haven't returned to pre-COVID levels, but we're seeing good momentum this year.

Peter Richard Lawson -- Barclays Bank -- Analyst

Thank you. And then were there any disruptions or departure on the sales front in the quarter? Just from the transitions we've seen at the management level?

Richard Paulson -- President and Chief Executive Officer

Sorry, Peter, can you just repeat that?

Peter Richard Lawson -- Barclays Bank -- Analyst

Just listing, have you seen any disruptions or departure on the sales front in the quarter or just from the transitions and changes that have been implemented from the management side?

Richard Paulson -- President and Chief Executive Officer

Yeah, so Peter, I think with regards to our staff and our team, we have really good momentum with regards to our teams. And we were able to bring a number of people on board over the last 12 months. And as we're implementing the changes, we're getting very positive feedback on them is it really is enabling, the sales organization and the marketing organization, both to report in directly to me, they are very streamlined to make sure we're focused on execution.

Peter Richard Lawson -- Barclays Bank -- Analyst

Thank you. And is there anything you can say around, I guess, either repeat prescriptions of physicians that are kind of represcribing the kind of, the most likely the same store growth number.

Richard Paulson -- President and Chief Executive Officer

Yes, I think, we have some real really good data on that and I'll turn to Sohanya on it. But when you when you look at the multiple myeloma market, it is a market, which is relatively concentrated and that you have about 80% of your business in about 1,000 accounts across the country. So maybe with that Sohanya, you can talk to some of our prescribing metrics and the impact we're having.

Sohanya Cheng -- Senior Vice President of Sales and Commercial Operations

Yeah, absolutely. So we've seen about -- in total about 1,000 total unique accounts that order to-date. This is primarily growth in the community clinics, but also we're seeing it in the academic setting. And as Richard pointed out earlier, the business is quite concentrated in these top accounts. And we are increasing and growing in our penetration in these top accounts.

Peter Richard Lawson -- Barclays Bank -- Analyst

Okay. Thanks so much.

Operator

We'll take our next question from David Lebowitz from Morgan Stanley. Please go ahead, sir. Mr. Lebowitz, are you there?

David Neil Lebowitz -- Morgan Stanley -- Analyst

Sorry, I was muted. When looking at the quarterly performance, how is performance in the original approved indication going at this point, assuming that you're getting some concrete share from Boston? Is there a kind of a max steady state for the original penta-refractory? Or how are -- is usage changing in that particular area?

Richard Paulson -- President and Chief Executive Officer

Thank you, David. I think as I mentioned before, it is hard. And there are no quantitative metrics to look at what line of therapy specifically. But I think again, it goes back to what I talked about with regards to the amount of new patients we're seeing initiated on XVd, which is our triplet store and triplets at the once weekly 100 starting dose. And again, in the first half of last year, about 50% of patients were started on the 100 and about 50% were started on the twice weekly 160. Whereas now on the first half of this year we have 85% starting on the once weekly dose, and only 15% on the on the 160 twice weekly. So I think that is seeing a strong shift into the triplet and into our once weekly business.

David Neil Lebowitz -- Morgan Stanley -- Analyst

I guess, my question is, is what would then be the driver, I guess, the decline in the original population as opposed to just maintaining a steady state?

Richard Paulson -- President and Chief Executive Officer

I think, David our focus is really on moving up into earlier lines. So that's where we're focused with regards to our promotional efforts and our education efforts. So that's an active strategy. And I think as Sohanya talked about, that's really where we also see a significant opportunity with regards to that second line plus setting. So in between the second and fourth line, patients 80% plus of patients, through the first two lines you can have immediate PI and anti-CD38. And physicians, really want to be able to bring in down board a class switch, which is why they're using all those agents upfront. And we have the ability as the first new agent in the last five years in that second and four line for a class switch with great efficacy. So our focus is in the earlier lines.

David Neil Lebowitz -- Morgan Stanley -- Analyst

Thanks for taking my questions.

Richard Paulson -- President and Chief Executive Officer

Thanks.

Operator

We will take our next question from Eric Joseph from JPMorgan. Please go ahead.We will take our next question from Eric Joseph from JPMorgan. Please go ahead.

Eric William Joseph -- JPMorgan Chase -- Analyst

Good morning. Thanks for the questions. Maybe, just picking up on that last question. Your breakdown of use between the once weekly in combination versus with dexamethasone, I guess, just how does square that with a pretty consistent duration therapeutic to the entity point 2.9 cycles. I would think sort of kind of moving to that combination regimen might extend a little bit further. What are you seeing in terms of discontinuation brace the tolerability? And then I have a follow-up.

Richard Paulson -- President and Chief Executive Officer

Sure. Thanks. So I'll start and I'll turn to Sohanya. Again, I think as we highlighted in part two, as we move into earlier lines, you will see length of therapy will evolve. And that takes time, and there's a few factors which weigh into that. Sohanya can talk to the factors which drive duration.

Sohanya Cheng -- Senior Vice President of Sales and Commercial Operations

Yes. Absolutely. So as I mentioned, there's really two drivers of discontinuation and our discontinuation rates has been maintaining at 12% to 13% consistent with the prior quarter. Now the two drivers here are side effect management and disease progression. And as we are moving into earlier line, as you mentioned with the once weekly triplet regimen, and we're proactively educating on side effect management and appropriate dose reduction to optimize the side effect management, as well as movement into earlier lines, we're going to see movement over time in the duration of therapy. We are still early in the launch and it takes time for that data to mature.

Eric William Joseph -- JPMorgan Chase -- Analyst

Okay. I guess how -- I guess in unpacking your comments about steady growth expectation, steady expansion into earlier line, I guess, how should we interpret that kind of in line with this kind of mid single-digit quarterly growth expectation? Is that fair? I guess, is there any selective growth expectation in several quarters out? And I guess as also as a relief to the endometrial cancer opportunity and SIENDO. Can you just talk a little bit about sort of tolerability expectations there as a comparison with the myeloma experience, as we expect either better or worse or in line tolerability to be intended compared to as active treatment?. Thanks.

Richard Paulson -- President and Chief Executive Officer

Thanks, Eric. I'll just start on the first part then I'll turn to Jatin to talk to endometrial. We're not going to give guidance kind of moving forward. It's still very early in our second-line launch. Going back to Sohanya's point, I think our 33% demand growth year-to-date versus the same period last year shows very strong demand growth. And we're moving up into earlier lines and feel very confident on our continued progress and into earlier line. And Jatin can you talk to the endometrial?

Jatin Shah -- Executive Vice President, Chief Medical Officer

Yes, I'm sorry. I cut out for a quick second. What was the question again regarding endometrial?

Richard Paulson -- President and Chief Executive Officer

Just endometrial and tolerability, and you can talk to the dosing that we're seeing -- that we're putting in place?

Jatin Shah -- Executive Vice President, Chief Medical Officer

Yes, absolutely. Good question. It's important to really highlights where we're going with XPOVIO and the schedule on dose, we really transition from high dose twice weekly to once weekly low dose. And that's what we're doing with the SIENDO study where we're dosing patients with 80 milligrams once weekly in the maintenance setting. And so we find that doses schedule, it's well tolerated, and many of our oncology line, oncologists are comfortable with XPOVIO management of side effects, and support of care there. And so many of our solid tumor I think are very comfortable managing nausea and vomiting. And with these low doses, we see a lower incidence of nausea and vomiting. So you'd expect.

Eric William Joseph -- JPMorgan Chase -- Analyst

Okay. Great. Thanks for taking the questions.

Operator

We'll take our next question from Jonathan Chang. Please go ahead, sir -- with SVB Leerink.

Wei Ji Chang -- SVB Leerink -- Analyst

Hi. Thanks for taking my questions. First question. In the past comments have been made regarding seeing the benefits of a longer duration of treatment associated with earlier lines in the second half sales numbers. Is that something that investors should still be expected?

Richard Paulson -- President and Chief Executive Officer

Yeah. Thanks, John. I think as we've said, as we move up into the earlier Alliance, we will see that progress, and we're seeing that, so we expect to start seeing that come through into the second half of the year, and it continues to move forward. Again, earlier lines with longer duration of therapy. The overall duration of therapy across the whole portfolio of patients that takes longer to shift as you balance innovations from later lines and earlier lines.

Wei Ji Chang -- SVB Leerink -- Analyst

Got it. On the second question for endometrial cancer, I understand we don't have the SIENDO results yet, but can you discuss the reasons for confidence that XPOVIO could achieve commercial success in that setting? If the study is indeed positive, and the drug is approved?

Richard Paulson -- President and Chief Executive Officer

Yeah. So I think you know, I'll kick it off. Then I'll turn to Jatin to talk about kind of the current impact of patients in that area and what we would expect to see looking at how we power the study with their and hazard ratio. So again, in the maintenance setting, there are no approved therapies. So to have the ability to benefit patients in that setting was a positive study, I think you would see a very rapid uptake, just as we've seen in ovarian cancer with the PARP's. And so Jatin, maybe you can talk to kind of the current expectations for patients and what were power to and what we would love to see,, if the study was positive?

Jatin Shah -- Executive Vice President, Chief Medical Officer

Yeah. Absolutely. So I mean, the powers phase the hazard ratio of 0.6. And we had our first interim analysis in November of 2020 as we mentioned. We passed and continue the trial as designed and expect top line results by the end of this year. If we have a positive study, with a hazard ratio of 0.6 or less, that will be both statistically as well as clinically significant for patients. Mind you, that's in the setting where there is no other approved maintenance therapies in endometrial cancer and a place that people are looking for maintenance. And the GYN oncologists are comfortable using maintenance therapy, as Richard alluded to so.

Operator

We'll move on to our next question from Colleen Kusy with Baird. Please go ahead.

Colleen Margaret Kusy -- Robert W. Baird -- Analyst

Hi, good morning. Thanks so much for taking our questions. See, you've talked about increasing confidence from physicians, I guess, can you talk a little bit more specifically about what you think is driving that increase in confidence? And then you also mentioned fine tuning the messaging and positioning? Can you provide a little more color on, how do that shift that you're putting out there?

Richard Paulson -- President and Chief Executive Officer

Hey, Colleen. Yeah, I'll turn to Sohanya for that.

Sohanya Cheng -- Senior Vice President of Sales and Commercial Operations

Thank you, Richard. So let me tackle your question in two parts. So the first is, is around the intent to prescribe data and the improvement in the perception. So when we assess the improvement or the change in perception among a broad range of physicians, both in the community and academic setting, on their perception on both efficacy attributes, the variety of efficacy attributes, as well as tolerability attributes, including GI toxicity, as well as the patient's impact on quality of life. And across all these metrics, across all lines overtime in the first half of this year, we have seen an improvement in the perception of the overall product profile. Regarding your second question on messaging and positioning, we are moving steadily from the penta-refractory original label to now the once weekly label in the earlier line setting. So, as I mentioned earlier, is quite a crowded marketplace in the fourth line plus with many options there. And in the first and second line, we've got also several classes there including the anti-CD38 PIs in it. However, there is this unmet need, this gap, this white space in between the second line and fourth line, where there is a need for a class switch or a new class of therapy, where it can have an impact on patients' outcomes. And this is where we are positioning XPOVIO with its efficacy and strong tolerability profiles, as well as the canal [Phonetic] convenient once weekly dosing options, we're positioning it in that white space.

Colleen Margaret Kusy -- Robert W. Baird -- Analyst

That's really helpful. Thank you. And then, could you also just clarify the inventory impact you saw in the quarter with the introduction of the New Strength Tablets? And then, how would you expect the New Strength Tablets to impact the monthly cost per patients?

Richard Paulson -- President and Chief Executive Officer

Sure, I'll take that. Yes, so that the impact is around $2 million for the quarter. So, as Sohanya mentioned earlier, we rolled out three New Strengths in June. So, it was a reset for customers. We do expect to be a one time thing this quarter. So, we wouldn't see that going forward in Q3 or Q4 of this year. And as far as net cost to patients, like I said earlier, we do -- we're at 21% gross to net in Q2, but we do expect that to come down in the second half of the year on an annualized basis will be somewhere between 15% and 20% for the year.

Colleen Margaret Kusy -- Robert W. Baird -- Analyst

Great. Thanks for taking my questions.

Operator

And there are no further questions at this time. We'll turn the floor back over to Mr. Paulson for closing remarks. Please go ahead.

Richard Paulson -- President and Chief Executive Officer

Thank you, very much, operator. I'd like to thank everyone for joining us for the Q2 call today. Again, as an organization and team at Karyopharm, we're very excited about the progress we continue to make in order to expand our breadth and depth in multiple myeloma to continue to expand our pipeline, both in hematological and solid tumor indications. And we're looking forward to coming back and sharing at our investor day in Q4 with regards to our strategic priorities and our prioritized pipeline. With that, thank you, operator and thank you for joining the call.

Operator

[Operator Closing Remarks]

Duration: 56 minutes

Call participants:

Joseph Rayne -- Vice President

Richard Paulson -- President and Chief Executive Officer

Sohanya Cheng -- Senior Vice President of Sales and Commercial Operations

Jatin Shah -- Executive Vice President, Chief Medical Officer

Michael Mason -- Chief Financial Officer

Unidentified Participant

Brian Corey Abrahams -- RBC Capital -- Analyst

Peter Richard Lawson -- Barclays Bank -- Analyst

David Neil Lebowitz -- Morgan Stanley -- Analyst

Eric William Joseph -- JPMorgan Chase -- Analyst

Wei Ji Chang -- SVB Leerink -- Analyst

Colleen Margaret Kusy -- Robert W. Baird -- Analyst

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