Good morning. My name is Matt. I will be your conference operator today. At this time, I would like to welcome everyone to Karyopharm Therapeutics' XPOVIO expanded approval conference call. There will be a question- and- answer session to follow. Please be advised that this call is being recorded at the company's request. I would like now to turn the conference over to Mr. Ian Karp, Karyopharm's Senior Vice President, Investor and Public Relations. Please go ahead.
Thanks so much, Matt, thank you all for joining us on today's conference call to discuss the expanded FDA approval of XPOVIO for the treatment of patients with multiple myeloma who have received at least one prior therapy. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, Chief Executive Officer, Dr. Sharon Shacham, President and Chief Scientific Officer, Mr. Sohanya Cheng, our Chief Commercial Officer, and Michael Mason, our Chief Financial Officer. On the call today, Dr. Kauffman will reveal details regarding the expanded approval of XPOVIO for the treatment of adult patients with multiple myeloma and will describe some of the key clinical features from the updated label, which will help us differentiate XPOVIO in the current multiple myeloma treatment landscape.
Following Dr. Kauffman's remarks, Sohanya Cheng will highlight the commercial positioning for XPOVIO in this new and expanded indication and where we believe the once-weekly XPOVIO, Velcade and dexamethasone regimen will be particularly appealing for physicians and patients. We will then open up the call to answer your questions. Earlier today, we issued a press release detailing the FDA approval of an expanded XPOVIO label. This release, as well as this webcast presentation, are available in the investor section of our website at karyopharm.com. Before we begin our formal comments, for those following along on the slide presentation, please turn to slide three. 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.
These include statements about our future expectations, clinical development, regulatory matters, timelines, potential success of our products and product candidates, including our expectations related to the commercialization of XPOVIO, 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 quarterly report on Form 10-Q, which has been filed 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, and 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 the forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Dr. Michael Kauffman, our Chief Executive Officer.
Thank you, Ian, and great afternoon to everybody. We are absolutely delighted today to announce that the FDA has now approved once-weekly oral XPOVIO for patients with multiple myeloma as early as first relapse, significantly expanding the patient population to whom we can now offer a new important treatment option. More specifically, XPOVIO is now indicated in combination with once-weekly bortezomib, also known as Velcade, and low-dose dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. We call this regimen XVD or XPOVIO-Vel-Dex. This latest indication is now XPOVIO's third FDA approval in less than two years and its first full approval. The previous two indications in myeloma and DLBCL were approved under the FDA's accelerated approval program and contingent upon verification of clinical benefit from a confirmatory trial. Today's news is also a critical development from a regulatory standpoint.
Additionally, this is now XPOVIO's first approval as part of a combination regimen with another potent anticancer therapy, and this is ultimately where we see the future for XPOVIO, namely as a partner of choice with other active anticancer medicines. XPOVIO, of course, is the only approved drug that specifically targets the XPO1 protein. XPO1 overexpression is observed across numerous tumor types, both in hematologic as well as solid tumors, and as a fundamental driver of cancer. XPO1 carries tumor suppressor proteins out of the nucleus, which results in the activation of these natural cancer-fighting molecules. XPOVIO treatment leads to the retention of a large number of tumor suppressor proteins in the nucleus, leading to their functional activation.
Based on this important and fundamental mechanism of action, XPOVIO has demonstrated synergistic activity in combination with many different drugs, including Velcade, an important part of the regimen approved by the FDA today. Please now turn to slide five. As expected, there is also important safety information included in the updated XPOVIO product label. Notably, there are still no black box warnings or contraindications in the label. A patient medication guide is available to educate patients on the expected adverse reaction profile for XPOVIO. Additionally, there are some important details regarding patient monitoring instructions and warnings and precautions included. All of these details are consistent with the safety information previously included in XPOVIO's label based on its accelerated approval last year for the treatment of patients with penta-refractory myeloma.
We continue to expect that these instructions, including the recommended supportive care guidelines and dose modification criteria, to be straightforward and easy for healthcare providers and patients to follow. Importantly, the dose of XPOVIO approved in this new expanded indication is 100 mg taken only once per week, as compared to the 80 mg twice-weekly dose, which was previously approved. The lower dose and the simple once-weekly administration is associated with improved tolerability with fewer adverse events as compared with the previously approved regimen. This newly approved once-weekly XVD regimen can be used in any patient with at least one prior therapy. Finally, it's recommended that adverse reactions be addressed using dosage modification standard supportive care with specific recommendations for both included in the prescribing information. Complete details of these guidelines, along with the complete information, can be found at www.xpovio.com.
Moving now to slide six, you'll get a sense of just how much larger the expanded patient population is for this new indication relative to XPOVIO's previously approved penta-refractory indication. In 2020, there are estimated to be over 20,000 multiple myeloma patients being treated in a second-line setting and over 12,000 patients treated in the third-line setting, as well as 6,000 or more in the fourth-line+ setting. Additionally, these numbers continue to grow each year due to both the increasing incidence of myeloma, but also because newer and more effective myeloma drugs are keeping patients alive longer, which is a wonderful achievement for the greater multiple myeloma community. These numbers greatly expand on the prior indication of XPOVIO in only penta-refractory or fourth-line-plus patients.
As we move to slide seven, I'll briefly highlight some of the key differences between the STORM study, which served as the basis for XPOVIO's accelerated approval in patients with penta-refractory disease, as compared to the BOSTON study, which supported today's expanded approval. As you can see, the patients who participated in the BOSTON study had received far fewer therapies than those in STORM and had myeloma that was far less refractory to treatment. Specifically, patients in BOSTON had a median of two prior therapies as compared to eight prior therapies in STORM. In BOSTON, the median progression-free survival and the response rate, as well as the time on selinexor seen in the BOSTON study, was substantially higher than in the STORM study.
This was also driven by the mechanistic approach of combining two drugs with different mechanisms of action in the BOSTON study, such as XPOVIO, an XPO1 inhibitor, given in combination with once-weekly Velcade, a proteasome inhibitor, along with dexamethasone. To reiterate, the mean duration of treatment was 10 months in the BOSTON study as compared to three months in the STORM study. This comparison of studies is key to why we believe XPOVIO has just begun to make an impact on the treatment paradigm in multiple myeloma. We believe the greatest utility for XPOVIO in the future will be as a combination therapy with other potent anti-myeloma drugs, such as Velcade, and taken only once per week instead of the currently approved dose of twice per week.
As we move to slides eight and nine, I will highlight some of the critical data from the BOSTON study that is most important to treating physicians. Once-weekly oral XPOVIO plus once-weekly Velcade and low-dose dexamethasone delivered an early and sustained progression-free survival advantage compared to twice-weekly Velcade and dexamethasone. More specifically, the XVD regimen demonstrated a 30% reduction in risk of disease progression or death and demonstrated a median progression-free survival of 13.9 months compared to 9.5 months in the VD arm. Only one of the nearly 200 patients of the XVD arm in BOSTON actually progressed, as compared to 10 on the VD arm. What makes these results even more impressive is that in the study arm with XPOVIO, Velcade, and dex, the Velcade was dosed at only once per week, so the patients received approximately 40% less Velcade.
Along with this, they received 25% less dexamethasone as compared with the control arm. In addition, patients receiving XPOVIO had approximately 35% fewer clinic visits compared to those who received standard twice-weekly Velcade regimen. In fact, this is the first phase III trial of a Velcade-based regimen that utilized only once-weekly Velcade in the experimental arm for patients with previously treated myeloma. This is critical because many physicians employ only once-weekly Velcade in combinations in general clinical practice. Responses observed with oral once-weekly XPOVIO plus VD were also rapid and durable compared to twice-weekly VD. More specifically, the median time to a partial response or better was just 1.4 months on the once-weekly XVD regimen compared to 1.6 months on VD, and the median duration of response was 20.3 months on XVD compared to 12.9 months on VD.
Additionally, the depth of response observed with once-weekly XPOVIO plus VD was significantly longer, higher than twice-weekly VD. The overall response rate was 76.4% on XVD compared to 62.3% on VD. Even more importantly, the rate of deep responses as defined by a very good partial response or better, meaning at least a 90% reduction in myeloma levels, was 44.6% for patients on the XVD arm compared to 32.4% on the VD arm. Finally, higher response rates were observed regardless of prior therapies received, the presence of high-risk cytogenetics, which occurred in 50% of the patients on trial, patients with renal impairment or advanced age, and this is very important as our commercial team now goes out to educate treating physicians on XPOVIO's updated indication and label.
Moving to slide 10, I'll also highlight the key safety data from the BOSTON study, now included in the updated XPOVIO product label. The most common adverse events, over 20%, in patients with myeloma who received XVD are fatigue, nausea, reduced appetite, diarrhea, peripheral neuropathy, upper gastrointestinal infection, decreased weight, cataracts, and vomiting. The most common Grade 3/4 laboratory abnormalities are thrombocytopenia, lymphopenia, neutropenia, anemia, and low sodium. These adverse events were generally self-limiting, reversible, and proved manageable with dose modifications and supportive care.
Most of the cytopenias were not accompanied by clinical sequelae. Importantly, the once-weekly XVD regimen resulted in significantly lower rates of peripheral neuropathy compared to the control group receiving twice-weekly Velcade. This is a particularly important feature, as peripheral neuropathy is one of the most common causes of treatment limitation and discontinuation for all VD combination regimens and for VD itself. The rate of Grade 2 or higher peripheral neuropathy, which was a pre-specified secondary endpoint in the BOSTON trial, was significantly lower in the XVD arm. This is particularly important and one which we believe will be well-received by both patients and physicians alike. With my review of the clinical data and label now update complete, I'd like to ask Sohanya Cheng, our Chief Commercial Officer, to highlight some of the key commercial messaging we plan to employ beginning today. Cheng?
Thank you, Michael, and let me echo your excitement and sentiments on just how important today's announcement is for the myeloma community and the Karyopharm commercial organization's ability to serve as many patients as we possibly can in their fight against this unfortunately far too common blood cancer. As we move to slide 11, I will highlight some of the key messaging our team will be taking to healthcare providers and patients. First, as you may know, there are currently a number of different therapeutic options available to myeloma patients in the second and third-line settings. It will be critical for Karyopharm to clearly highlight the key unmet need that XPOVIO can help address. Importantly, in multiple myeloma, we believe treating with different mechanisms as early as possible is vital for success.
Thus, one of the key advantages XPOVIO brings is a novel mechanism of action that is synergistic with a proteasome inhibitor like Velcade. The primary focus of our messaging will be on the efficacy and safety XPOVIO demonstrated in the pivotal BOSTON study. The weekly XPOVIO plus VD regimen conferred a rapid and sustained PFS benefit, and patients achieved a clinically significant durable response with once-weekly XPOVIO plus VD, regardless of cytogenetics, renal impairment, or prior therapeutic exposure. Of course, XPOVIO is the first and only FDA-approved oral XPO1 inhibitor that gets to the cell's nucleus, which leads to cell cycle arrest and apoptosis in cancer cells. In fact, it is the first new mechanism approved since 2016 for the treatment of myeloma patients who received at least one prior line of therapy and has a strong synergistic effect with proteasome inhibitors, leading to cancer cell death.
Another important feature for the once-weekly oral XPOVIO plus VD regimen is that it can reduce the burden of having to come to the physician's office or hospital clinic for twice-weekly Velcade injections. Moreover, many patients may prefer an oral drug option to other options that require intravenous infusions at the hospital or physician's office, which can mean many hours spent in the clinic. Also, our discussions with healthcare professionals will include the manageable safety profile the weekly XPOVIO plus VD offers to a broad range of patients and a side effect profile that is reversible and manageable with dose modifications and supportive care. Finally, as I move to slide 12, let me explicitly identify the kinds of patients that we believe physicians are most likely going to consider for treatment with the newly approved once-weekly XPOVIO plus VD regimen.
These include patients who received REVLIMID and DARZALEX in the frontline setting and are Velcade naive following their first relapse. Patients who received only a short course of Velcade in the frontline setting prior to a stem cell transplant, and thus may be appropriate to receive another course of a Velcade-based regimen. Patients who have high-risk disease and/or cytogenetic abnormalities, patients who have renal dysfunction, patients who prefer once-weekly oral drug and once-weekly injection rather than IV infusions or more frequent visits to the clinic. Finally, patients who might benefit from a drug with a completely novel mechanism of action that is synergistic with a proteasome inhibitor. In summary, we believe there are many different types of patients who can benefit from XPOVIO plus VD therapy, and we can't wait to meet with our customers and begin to educate them on this new, expanded, and exciting indication.
We believe this new indication will allow us to greatly increase our recent sales trajectory and significantly expand XPOVIO's peak sales potential. With that said, we are, of course, still in the midst of a surge in the global COVID pandemic, so patient visits to their physician offices may remain impacted, and we will continue to largely access our customers via digital methods over the next handful of months. Once our sales force can get back to regular face-to-face interactions with customers, we believe we will be able to drive even greater adoption of the once-weekly XPOVIO plus VD regimen. With that, we would now like to open the call up to questions. Matt, turn it over to you for Q&A.
We will now begin the question- and- answer session. To ask a question, you may press star then one on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. Please limit your questions to one question and one follow-up so that everyone may have an opportunity to ask this question. At this time, we will pause momentarily to assemble our roster. Our first question comes from Maury Raycroft with Jefferies. Please go ahead.
Hey, everyone. Much congrats on the update today. I guess first question is just on you getting this approval earlier than expected. Wondering if you can comment on just preparedness for the expansion, both supply and commercially. Are you full go right now, or what do you have to do in order to get to the full go stuff from a commercial standpoint?
Thanks, Maury. We've been working very closely with FDA on this. The trial was clean and clear. The review was very expeditious by the agency back and forth. There was absolutely no slowdown. If anything, there seemed to be an acceleration. Obviously, the FDA is well acquainted with this drug. This is our third approval with the same division. Of course, the side effect profile, despite the fact that this treatment is more than three times longer than the previous two approvals, the side effect profile is better than the previous approval. That was easy there. Clearly we hit the primary and many of the secondary endpoints. We've had a very good interaction with the agency. I think they're thrilled that this confirmed their initial decision to approve the drug in the accelerated approval fashion, both literally confirmed it and legally confirmed it.
Now we've been ready for a while now, gearing up for this from the commercial side. I'll turn it over to Cheng now, but I can say the preparation on the commercial side as well as on our medical science liaisons, our nurse practitioners who work in here, and all of our groups in commercial have been just great. Cheng?
Yeah. Thank you, Michael. In order to ensure we could bring this advance to patients immediately at approval, we set a launch readiness date well in advance of the due date. All of our teams have been trained, the sales teams, the nurse teams, our market access teams, our medical science liaison teams, and they're ready to fully go as of today. We prepared all of our materials in advance, and we'll start rolling those out within the next few hours so that we can immediately start communicating the good news and educating physicians. Good news is we're ready to go across functions, and that begins right now.
Great. Maybe just a quick follow-up. You also had the NCCN guideline update recently, too. In addition to XVD, you've got XPD and XDD added to the NCCN guidelines. Just wondering how that's going to factor in commercially, how that could come into play for prescribers.
Sure. Thanks. Just to be clear, our sales and marketing teams will, of course, only promote XPOVIO based on the approved FDA label, which obviously now includes the combination with bortezomib dex for the treatment of patients with myeloma who've received at least one prior therapy. That regimen can be used in anyone that is getting second-line or later therapy in myeloma. It applies to everybody. We do know that many physicians, and particularly the payers, rely on the NCCN guidelines to help them make treatment decisions, like you said. As you know, the NCCN recently added the XVD combination to the guideline with a Category 1 recommendation, meaning the strongest recommendation for treatment of relapse disease.
They also, based on the presented phase I/II data and the very high response rates and progression-free survivals, they added the XDD, the selinexor, daratumumab, dexamethasone combination, and the XPD or selinexor, pomalidomide, dexamethasone combination. This latter combination, importantly, is one of the most potent all-oral regimens for the treatment of relapsed myeloma. It can be very convenient, particularly in the setting of the pandemic, but if you just think about it outside the pandemic, for patients who have a long distance to travel and would prefer an all-oral regimen and not have to visit the clinic. All of these regimens are now in the NCCN.
In addition to that, we're already aware of a significant minority of patients who are receiving XVD prior to today as well as other X combinations, XPOVIO combinations, including with KYPROLIS and REVLIMID, and these have been generally reimbursed without any trouble. Previously, they were only reimbursed in the penta treatment setting, but now we believe that the combination regimens would be reimbursed even in the second-line setting, as is typical with other myeloma drugs. We just close this by reiterating again that the commercial team will only promote based on the FDA label.
Got it.
Does that answer?
Thank you very much.
Great.
Yeah, that answers it.
Sure.
Congrats again.
Our next question comes from Brian Abrahams with RBC. Please go ahead.
Hi, this is David Dusu on for Brian. Thanks so much for taking my question. Congratulations again on this early approval. Great way to cap off 2020. I just have, I guess one question, and then maybe a quick follow-up. Just looking at slide 12 again on the types of patients that your market research suggests might most likely prefer XPOVIO in the earlier line setting, could you speak a little bit to how maybe you're aligning or realigning the commercial strategies for this expansion relative to the penta-refractory setting? Maybe, for example, you might find more of these patients in the community setting? Thanks.
Yeah. Yes, you're correct. About 75% of these patients are in the community setting, and we have updated the positioning and the strategy accordingly to drive the combination therapy, and we've trained the teams as such. As we've done significant amount of market research and a number of ad boards, the patients you see here are all types of patients that both community oncologists and the academic oncologists said would be appropriate for this new XVD regimen.
Got it. Maybe just to follow- up a little bit on Maury's last question on NCCN and access, I guess, could you speak a little bit to the expected cadence of access here? For example, might we perhaps see a bit of a bolus initially with immediate access enabled by NCCN, followed by your typical kind of slower expansion of access as plans work through the approval and work XPOVIO earlier line into their policies?
I think the reality is, as I'm sure you appreciate, payers have their own individual policies and some will follow NCCN, some won't. Ultimately, obviously, we're thrilled with the approval today, and clearly, especially with the NCCN Category 1 designation, there's a clear benefit from the XPOVIO VD regimen. Let's let time tell and individual payers and physicians, as they get more and more experience with XPOVIO, they'll be the ultimate deciders of exactly how and where they plan to use it. At this stage, we wouldn't be prepared to project what a cadence of sales or reimbursement policies might look like. That'll take some time to see.
Got it. Understood. Thanks.
Our next question comes from Jonathan Chang with SVB Leerink. Please go ahead.
Hello, this is John Barrett on for Jonathan. Congrats on the approval. Your press release mentions you're still working with the EMA on a decision there. Is that decision still expected by year-end? If not, what are your discussions sort of centering around, and do you have any updated thoughts on your launch plans for Europe?
Sure. Yeah, we can update on that. Our discussions with CHMP and EMA have progressed regarding the approval of XPOVIO in patients with penta-refractory myeloma. They are ongoing at this time, and we do expect to receive a definitive decision in January of 2021. Additionally, we do expect to submit the separate MAA-based, medicines agency application for XPOVIO approval based on the BOSTON study population shortly after we have the definitive decision from CHMP or EMA. We'll update for sure when we learn more. I'll turn it over to Mike Mason to just comment on the launch in Europe and the plans in Europe.
Sure. We see the real value in Europe from a commercialization perspective, really post-BOSTON approval. We're certainly targeting being commercial ready, whether on our own or with a partner when BOSTON will get approved and essentially get approved in Europe.
Got it. That's helpful. Thank you. Just one more follow-up. Given we're near the end of 4Q, can you provide any color on the sales trajectory for XPOVIO through October and November? Do you expect to provide preliminary unaudited 4Q numbers at JPM like you did last year.
Yeah, I think at this stage, we're not really able to provide much detail on Q4 sales because clearly there's still a few weeks left in the quarter. We're focused obviously right now on the launch of BOSTON. We do expect to provide some additional guidance at the J.P. Morgan conference. We have a scheduled presentation that's been confirmed for January 11th, I think that's probably a more appropriate time to give an update there. Importantly, though, clearly today's approval from the FDA will allow us to immediately provide access to a significantly expanded patient population. As we move into the Q1 , that's obviously the key and most important thing that we'll be working on.
Awesome. Thank you very much.
Our next question comes from David Lebowitz with Morgan Stanley. Please go ahead.
Thank you very much for taking my question. When you look at launching into the BOSTON population pushing earlier in line, how do you see it moving into second line versus third line as far as physicians, I guess, employing it, given especially that there's been a lot of movement of the various therapies that are already being used in those earlier lines and shuffling as far as how they're being used currently?
Yeah. I'll start and Cheng will follow- up. I think the considerations you saw on slide 12 are really relevant here. As you suggest, physicians have developed their preferred sort of first line, second line, third line regimen, and there are a lot of choices to make. Some of the considerations they'll be looking at as they think about use in second versus third line are really the ones that are up here. There is a desire in myeloma, as in most other cancers, to switch mechanisms when moving from one line to the next.
Certainly for patients who have REVLIMID, DARZALEX in the frontline setting who've not yet received a proteasome inhibitor, this combination can provide a really convenient and effective regimen in the second line, and it would make sense because you'd switch out the IMiD for a proteasome inhibitor, and the DARZALEX would switch out for selinexor. It is the only single once-a-week regimen that'd be approved in that second line. Then for patients who've received a transplant, either in first or second line, but only got a short course of Velcade prior to the transplant, we've shown really great activity. I think those are the two major indications for the use in second line. There are another subset of use of patients, though that can be done in second line who have specific issues, and we listed some of them here.
I'll turn it over to Cheng now to add to this.
Yeah. Thanks, Michael. We know from the market research and from the ad boards that physicians have an ingrained class switch behavior that they already deploy in the context of multiple myeloma, and they have a desire to use all backbones early in a patient's course of therapy. We're going to look at it on a patient-by-patient basis as we talk to our HCP customers, and we know XPOVIO will be used some in second line, some in third line. It'll depend on the sequence of drugs that they have. The primary goal, though, is to make sure they receive this new backbone, XPOVIO, before they're re-exposed to another PI, another IMiD, or another anti-CD38.
Thanks for taking my question.
Our next question comes from Eric Joseph with J.P. Morgan. Please go ahead.
Hey, guys. Congrats on the early approval here. Really great, and thanks for taking the question. Just from going through the label, it seems that there's a difference in the rate of all grade neutropenia relative to The Lancet publication. I'm seeing 48% versus 15% in the publication. What accounts for the discrepancy there? To what extent does neutropenia guide treatment selection in the earlier line when choosing between options in the earlier line treatment multiple myeloma setting? Thanks.
Yeah. We're not sure we really understand the issue. I think it's a Grade 3 versus Grade 3/4 versus overall grade. We'll get back to you on that, Eric. There was really no meaningful difference. It's a lower rate of neutropenia in general in the BOSTON study. Again, even with the three times longer treatment, just given the fact that our drug has minimal neutropenia associated with it. Velcade has a little bit, but not too much either. Can you just reiterate the second question you had?
Well, it's just related to whether the rate of neutropenia that's showing here in the label is going to have an impact on treatment decisions when choosing between options.
I think you have to remember for all cytopenias, first of all, hematology oncologists are very comfortable handling cytopenias. This is their bread and butter. This is what they absolutely know. These rates of overall neutropenia are really not relevant. What's relevant, as you know, in clinical practice, is Grade 3/4 neutropenia and, in particular, rates of febrile neutropenia. We have extraordinarily low rates of febrile neutropenia. Even in patients who have Grade 3/4 disease, primarily they receive G-CSF in various types, and they have a quick response. They don't tend to develop infections, and that's the thing that doctors most worry about. As you know, febrile neutropenia can be fatal and is a very significant issue, and we don't see it with this drug.
That does distinguish XPOVIO, and particularly the XPOVIO-Vd, from a lot of the other combinations, with an overall lower rate of neutropenia than many of them. The clinically significant neutropenia, Grade 3/4, and in particular, febrile neutropenia, really are not part of our typical adverse effect profile.
Got it. Thanks for taking the question, and congrats again.
I can say from the label, we had a 12% Grade 3/4 risk of neutropenia, and that's a very low level. I think that compares very favorably to the vast majority of the other triplet regimens.
Our next question comes from Peter Lawson with Barclays. Please go ahead.
Hey, thanks so much for taking the questions, and congratulations on the label expansion. Just, I guess firstly for Cheng, just thanks for highlighting the groups of patients that you target for SVd. Is there any way you could rank those or break out the number of patients that you could potentially address by going after those subgroups?
We've certainly done that internally in terms of ranking and giving a prioritization to the sales force. I don't think it's something that we want to provide publicly based on competitive reasons as to our ranking as to which patients are the primary target versus which patients are the secondary targets.
Great. Okay. Understand. Just going through the label, it seems that, I may be wrong on this, but cataracts were mentioned as a new precaution and low phosphate level. Just how we should think about that in the potential of using the drug.
Yeah. Ironically, the most common preexisting condition across both arms of the BOSTON study coming in was cataracts in over two-thirds of the patients. For reasons that remain unclear, we had a higher onset of late cataracts, typically after 24 weeks, as compared to what we've seen previously. Part of this is because we're giving longer therapy, the cataracts in both arms, but particularly in the XVD arm, are treated with standard cataract surgery, and this is the most common surgery in these older folks. We don't really understand the mechanism. It led to zero discontinuations. It actually led to a very tiny number of even dose modifications or missed dose because cataract surgery is so relatively straightforward and effective. The other one, the low phosphate is just something we've noticed. It has had no real impact in the study. We try to correlate.
Typically, you might see a slight increase in fatigue or muscle aches associated with that. Again, there was really no clinical associations with the phosphate decrease. I will address, if you can, I will just go back to Eric's question. The difference in the label, you are correct, is that the FDA has moved to laboratory abnormalities that are based purely on the laboratory results and not on whether the events were reported as adverse events. In the label, what you see is the actual count of people who had neutrophil counts decreased. What you saw in The Lancet paper with a number of 15% for all grade, was patients whose doctors reported this as an adverse event. That's consistent with what I said, which is to say that doctors really don't consider Grade 1 and 2 neutropenia to be an adverse event.
They note it. That's why The Lancet paper has a lower number. The Grade 3/4 events for both The Lancet and the packages differ slightly but are essentially the same, consistent with the notion that doctors will consider a Grade 3/ 4 neutropenia to be an adverse event. They're reported both as a number and as well as an actual AE. I hope that clarifies that. Peter, did you have another one? I'm sorry.
Yeah, just a quick question around the emergence of BCMA therapies and potential impact they could have on the use of selinexor, and then the potential for you to combine with those, if that's something you're thinking through.
I think the second part is easy. I mean, XPOVIO so far has been effectively combined with at least NCCN guideline support and publication support with all of the other major anti-myeloma drugs to- date. We know that these combinations are in use. We will be looking at the combination with BLENREP. We're aware of a couple of patients who appear to be receiving the combination already who have highly refractory myeloma. Our focus really now is on the BOSTON population, which is second-line and later as the XVD regimen on label, and of course, as doctors choose to follow the NCCN and other guidelines to go further. BLENREP is a good drug. It acts well.
I want to be clear that the ocular events that are seen with XPOVIO, which are cataracts, are not the same at all as the keratitis that's seen with BLENREP. I don't think that this will preclude the combination, and I think history and myeloma has told us that taking different mechanisms and combining them can lead to very good effects. At the end of the day, we want XPOVIO to be a partner for essentially any drug in myeloma, BLENREP included.
Got you. Okay. Thank you so much. Congrats.
Our next question comes from Ed White with H.C. Wainwright. Please go ahead.
Good afternoon. Thanks for taking my questions, and congratulations. Thinking about your market research, I'm just curious as to what you're seeing for Velcade use in the second and third line. The docs you talk to, is lowering the administration of Velcade that important to them that they would increase the use of Velcade in the second and third lines? The follow-up is just what you're expecting to see the impact on XPOVIO use in the penta-refractory if it's used in second and third line. Thanks.
Sure. Look, we think that having another option for Velcade combination has got to help patients, whether it gets used in second or third line, depending largely on what they got in first line, and also depending on things like renal dysfunction and high-risk cytogenetics. The use in the real world of Velcade in second and third line is almost always with once-a-week Velcade. It is used prevalently. I don't know that we'll increase necessarily the use of once-weekly Velcade in the second and third line. We do believe that selinexor, because of the new mechanism, because it's not affected by renal dysfunction, it is active in high-risk cytogenetics and so on, provides some really important and potentially very meaningful benefits to patients.
The last point to really hammer home, we're talking to physicians all the time, and this was seen at our advisory boards, is that the clinical data that came out of BOSTON are directly relevant to their clinical practice. This is the first phase III study that we're aware of in relapsed myeloma, where the results of a Velcade-based triplet regimen can probably move directly to their practice because all other Velcade triplets are studied with twice-weekly Velcade in the experimental arm, and really, you don't know what you're going to get in practice when you cut the dose of Velcade down by 40%.
The other thing we've learned to answer the second part of your question, we don't have a lot of great data on retreatment of selinexor, but the previous view and the emerging view for Velcade and even IMiDs and now more recently for DARZALEX or at least CD38 antibodies, is that somewhere between six-12 months hiatus for the reuse of drugs tends to allow for the tumors to reacquire sensitivity to those mechanisms. We wouldn't expect anything different regarding selinexor at this point, and we think that retreatment with XPOVIO-based regimens could happen in later lines, and we would generally say that based on history, some kind of a hiatus since the last time they received XPOVIO would be warranted, we don't have data yet to directly support that.
Great. Thank you, Michael.
As a reminder, if you have a question, please press star then one to be joined into the queue. Our next question comes from Arlinda Lee with Canaccord. Please go ahead.
Hi, guys. Congratulations on the early approval. I had a couple questions about, I know you guys are not promoting or do not promote off-label. I think in some of your earlier earnings slides, you had indicated things that would've suggested that you were getting off-label use. Do you think you can provide updates on that information? Maybe another way, can you talk about what the durability is on commercial drug currently? Lastly, can you maybe talk about feedback that you've been getting from KOLs and prescribing docs coming out of ASH? Thank you.
Let me start, then I'll turn it over to Ian and Cheng. I think when we get into the off-label discussion, we should just be clear that there's two aspects. One is the place in someone's therapy, in therapeutic journey that they get XPOVIO or any other drug. The penta-refractory label could come in as early as third-line therapy and can come on anytime later, provided they receive the five drugs that are on label. Generally, physicians and payers are okay with whatever cocktail is used in a line, provided it is for the patients that are on label. As you correct, we have said that a significant minority of patients have received triplet therapy, in the penta-refractory setting, and this was reimbursed very well across the country because it was applying to the patients who were in this penta-refractory group.
There's important to distinguish between the patient population and exactly what combination therapy they get. Typically, payers have left it up to the doctor, thankfully, to make those decisions to optimize therapy for the patient. Ian?
Maybe just a couple of points. In terms of future earnings presentations, I think we'll have to wait and see. Certainly there is, as you know, this is a competitive space with a number of branded drugs that we're now directly competing with. I think the types of commercial data that we show may or may not change. I think time will tell. I don't want to sort of promise anything, in terms of what future slides might look like. In terms of the durability, maybe I'll let Cheng talk about what he and his team are hearing, post ASH. What I will say is on our last earnings call, and in the presentation, we did provide the latest average number of cycles or average number of months of drug per patient within our specialty pharmacy network, and it was approaching three months.
That's consistent with what we saw in the STORM study, which was an average of about three months of treatment. I think now what you're going to, hopefully, what you'll see is as this drug moves in combination with bortezomib and moves earlier into earlier line therapy, and as Michael noted in the slide presentation, the average duration of treatment in BOSTON was 10 months compared to three months in STORM. We would expect to see the durability or the time on treatment to increase over time. Again, time will tell, and we won't have that data immediately. It will take a number of months to start probably seeing those kinds of averages increase. It's certainly our expectation that the average duration of therapy increases. I don't know, Cheng, if you want to comment on post ASH.
Thank you. Just to further address the comment on current use in the market and then post ASH, as Michael mentioned, most of our use is in the penta-refractory setting today. Most of that is fourth-line+ . The majority of that use is with the XD combination, with some limited use of XVD, which is why we're really excited now to get the approval of XVD and be able to promote that in the second, third-line setting, where the size of the patient population is roughly 6x the size of our prior indication. A much bigger opportunity to help patients.
Others can comment also, but I'd say the feedback we've heard post ASH in terms of one-on-one discussions in ad boards and different exchanges with our customers has all been very positive and people are ready and excited for the XVD data to be available to patients.
Great.
Next question.
This concludes our question- and- answer session. I would like to turn the conference back over to Michael Kauffman, CEO, for any closing remarks.
Thanks very much. I'll just close with saying that this is a great day for patients and their families and their physicians and other healthcare providers. For the patients with myeloma, a tough disease, but now they have a new and very convenient option to help them treat their disease. I do want to thank all of the patients and the healthcare providers, the KPTI staff, and especially the FDA for making all of this happen in such an expedited timeframe. I wish everybody happy holidays, and thank you again for joining us today. Have a great day.
The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.