Good morning. My name is Matt and I will be your conference operator today. At this time, I would like to welcome to everyone to Karyopharm Therapeutics ex Pavio 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 Senior Vice President, Investor And Public Relations. Please go ahead.
Thanks so much, Matt, and thank you all for joining us on today's conference call to discuss the expanded FDA approval of Xpobio 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 Doctor. Michael Kaufman, Chief Executive Officer Doctor. Sharon Schackham, President and Chief Scientific Officer Mr. John Demrey, our Chief Commercial Officer and Mike Mason, our Chief Financial Officer. On the call today, Doctor.
Kaufman will reveal details regarding the expanded approval and exposure for the treatment of adult patients with multiple myeloma, and we'll describe some of the key clinical features from the updated label, which will help us differentiate Fobio in the current multiple myeloma treatment landscape. Following Doctor. Kaufman's remarks, John Demry will highlight the commercial positioning for Expobio in this new and expanded indication. And where we believe the once weekly EXFOELCADE 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 Expedited label. This release, as well as this webcast presentation, are available in the Investors section of our website at karyopharm.com. Before we begin our formal and for those following along in the slide presentation, please turn to Slide 3. I'll remind you that various remarks we 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, Cliff of Milton, regulatory matters, timelines, potential success of our products and product candidates, including our expectations related to the commercialization of Xplio, 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 Ten Q, which is 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 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 Doctor.
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 Exposvio for patients with multiple myeloma as early as first relapse, significantly expanding the patient population to whom we can now offer a new treatment option. More specifically, Xpobio 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 1 fire therapy. We call this regimen XBD or Xpovio Vildex. This latest indication is now Xpovio's 3rd FDA approval, in less than 2 years and its first full approval.
The previous 2 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. Thus, today's news is also a critical development from a regulatory standpoint. Additionally, this is now Xplovio's first approval as part of a combination regimen with another potent anticancer therapy and this is ultimately where we see the future for Expevio, namely as a partner of choice with other active anti cancer medicines. Exposvio, of course, is the only approved drug that specifically targets the XP01 protein.
XP01 overexpression is observed across numerous tumor types, both in hematologic as well as solid tumors and has a fundamental driver of cancer. Xp01 carries tumor suppressor proteins out of the nucleus, which results in the activation of these natural cancer fighting molecules. Exposvio 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 5.
As expected, there is also important safety information included in the updated Expevio product label. Notably, there are still no black box warning block box warnings or contraindications in the label. A patient medication guide is available to educate patients on the expected adverse reaction profile for Expevia. 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 Espovio's label based on its accelerated approval last year for the treatment of patients penta refractory myeloma.
We continue to expect that these instructions, including the recommended supportive care guidelines of those modification criteria, to be straightforward and easy for healthcare providers and patients to follow. And importantly, the dose of Xplovio 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, improved tolerability with fewer adverse events as compared with the previously approved regimen. And this newly approved once weekly XPD regimen. Can be used in any standard supportive care with specific recommendations for both included in the prescribing information.
Complete details of these guidelines, along with the fleet information can be found at www.expobio.com. Moving now to Slide 6. You'll get a sense of just how much larger the expanded patient population is for this new indication relative to Expobia's previously approved femtorefactory indication. In 2020, there are estimated to be over 20,000 multiple myeloma patients being treated in the second line setting, and over 12,000 patients treated in the 3rd line setting, as well as 6000 or more in the 4th line plus setting. Additionally, these numbers continue to grow each year due to both 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 myeloma community.
These numbers greatly expand on the prior indication of Xpovio in only penta refractory or 4th line plus patients. As we move to Slide 7, I'll briefly highlight some of the key differences between the STORM study which served as a basis for Xprobio's accelerated approval in patients with phentar 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 2 prior therapies as compared to 8 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 2 drugs such as Xpovio and Xb01 inhibitor, and given in combination with once weekly Velcade proteasome inhibitor, along with dexamethasone. And to reiterate, the mean duration of treatment was 10 months in the BOSTON study as compared to 3 months in the STORM study. This comparison of studies is key to why we believe Expobio has just begun to make an impact on the treating paradigm in multiple myeloma. We believe the greatest utility for Xpobio 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 Slide 89, I will highlight some of the critical data from plus once weekly Velcade and low dose dexamethasone delivered an early and sustained progression free survival advantage compared to twice weekly vocated 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 BDR. And only one of the nearly 200 patients of the XVD arm in Boston actually progressed as compared to 10 on the VDR. And 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 that patients received approximately 40% less Velcade. Along with this, they received 25% less dexamethasone as compared with the control arm. In addition, patients receiving Expobio had approximately 35% fewer clinic visits compared to those who received standard twice weekly Velcade regimen.
In fact, this is the 1st Phase III trial of a Velcade based regimen that utilize only once weekly Velcade in the experimental arm for patients who previously treated myeloma. This is critical because many physicians employ only once weekly Velcade in combinations in general clinical practice. Response is observed with oral once weekly exposure, 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 BD and the median duration of response was 20.3 months on XVD compared to 12 point COBO plus BD was significantly longer, higher than twice weekly BD. The overall response rate was 70 0.4% on XPD compared to 62.3% on BD.
And even more important, the rate of deep responses as defined by a very good percent for patients on the Xbd arm compared to 32.4% on the VD arm. Finally, Our response rate to observe, 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 physician on Expobio'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 Descovyo product line, The most common adverse events over 20% in patients with myeloma, who we see DexPD, our fatigue, nausea, reduced appetite, diarrhea, peripheral neuropathy, upper gastrointestinal infection, decreased weight, cataracts, and vomiting. The most common grade 34 laboratory abnormalities are thromocytopenia, lymphopenia, neutropenia, anemia, and low sodium. These adverse events were generally self limiting, reversible and proved manageable with dose modifications in supportive care.
Most of the cytopenias were not accompanied by clinical sequelae. And importantly, the once weekly XVD regimen resulted in significantly lower rates of peripheral neuropathy compared to the control group receiving twice weekly belt This is a particularly important feature as peripheral neuropathy, neuropathy is one of the most common causes of treatment limitation and discontinuation for all VD combination regimens and for VD itself. Additionally, 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 John Demery, our Chief Commercial Officer to highlight some of the key commercial messaging we plan to employ beginning today.
John?
Thank you, Michael, and let me echo your excitement 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 options available to myeloma patients in the second and third line settings. So it will be critical for Keriopharm to clearly highlight see unmet need that Expevio can help address. Importantly, in multiple myeloma, we believe treating with different mechanisms as early as possible is vital for success. And thus, one of the key advantages Xpovio brings is a novel mechanism of action that is synergistic with a proteasome inhibitor like Velcade.
But the primary focus of our messaging will be on the efficacy and safety, Xpovio demonstrated in the pivotal loss in study. The weekly Xpovio plus BD regimen confirmed a rapid and sustained PFS benefit, and patients who achieved a clinically significant, durable response with once weekly expovial plus BD regardless of cytogenetics, renal impairment, or prior therapeutic exposure. And of course, Xpovio is the 1st and only FDA approved oral XB01 inhibitor that gets to the cell's nucleus, which leads to the cell cycle arrest. And apoptosis and 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 exposure plus BD 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 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 Folio plus CD offers to a broad range of patients and a side effect profile that is reversible, and manageable with dose modifications in 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 Expobio plus VD regimen. And these include patients who received Revlimid and DARZALEX in the frontline setting, or 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. And 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 EXPLOVIO plus BD therapy and we can't wait to meet with our We believe this new indication will allow us to greatly 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 Expoviobio plus BD regimen.
And with that, we would now like to open the call up to questions. Matt, turn it over to you for Q session.
Questions. 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. I'm wondering if you can comment on just preparedness for the expansion with supply and commercially, are you FOGO right now or what do you have to do in order to get to the FOGO supplement purchase? 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 3rd approval with the same division. And of course, the side effect profile, despite the fact that this this treatment is more than three times longer than the previous 2 approvals. The side effect profile is better than the previous approval. So that was easy there.
And then clearly, we hit the primary in many of the secondary endpoints. So 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. And now we've been ready, for a while now gearing up for this, the commercial side. I'll turn it over to John 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.
John?
Yes. Thank you, Michael. In order to ensure we could bring this to patients immediately at approval, we set a launch readiness stage well in advance of the PDUFA date. All of our teams have been trained. 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've prepared all of our materials advance. And you'll start rolling those out within the next few hours. So we can immediately start communicating the good news and educating physicians. So good news is we're ready to go across functions and that begins right now.
And maybe just a quick follow-up. You also had the NCCN guideline update recently to So in addition to SPD, the SPD and SDD added to the existing end guidelines, I'm just wondering how that's going to factor in, commercially how that could be, how that could come into play for the drivers? 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 bortez and dex for the treatment of patients with myeloma who received at least one prior therapy. So that regimen can be used in anyone that is getting second line or later therapy in myeloma applies to everybody. We do know that many physicians and particularly the payers rely on the N guidelines to help them make treatment decisions, like you said. And as you know, the NCCN recently added the X BD 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 1two data, and the very high response rates and progression pre survival as they added the Xdd, the selinexordaratumumab dexamethasone combination and the X PE or selinexorpalmolystexamethasone combination.
And this latter combination, importantly, is one of the most potent all oral regimens for the treatment of relapsed myeloma. So it can be very convenient, particularly in the setting of the pandemic, but just think about it outside the pandemic for patients who have a long distance to travel and would prefer, an oral regimen and not have to visit the clinic. So all of these regimens are now in the NCCN. In addition to that, we're already aware of 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 the pendant treatment setting, but now we believe that the combination regimens would generally be reversed, would be reimbursed even in the second line setting as is typical with other myeloma drugs. And we just close this by reiterating again that the commercial team will only promote based on the FDA label. Got it.
Thank you very much. Yes, that's correct.
Our next question comes from Brian Abraham with RBC. Please go ahead.
Hi, this is David Ciesou on for Brian. Thanks so much for taking my question and 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 Espovio 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 pensal refractory setting?
And maybe for example, you might find more of these patients in the community setting?
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 to drive the combination therapy, and we've trained the teams as such. As we've done a 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 XCD regimen.
Got it. And maybe just to follow-up a little bit on, Maury's last 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 MPCN followed by your typical kind of slower expansion of access, as plans work through the approval and work exposed in earlier lines into their policies?
Yes. I mean, 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. I think ultimately, obviously, we're thrilled with the with the approval today. And clearly, especially with the NCCN category 1 designation, there's a clear benefit from the EXFO VD regimen I think let's let sort of time tell and, individual payers and physicians as they get more and more experience with Xphobia. I think they'll be the ultimate deciders of exactly how and where they plan to use it.
So I think at this stage, we're wouldn't be prepared to kind of project what the cadence of sales are reimbursement policies might look like. That'll take some time to see.
Our next question
comes from Jonathan Chang with SVP 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?
And if not, what are your discussions sort of centering around? And do you have any updated thoughts on your launch plans for Europe?
Sure. Yes, we can update on that. So our discussions with CHMP and AMA have progressed, regarding the approval of Expobio in patients with panta 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 a separate MAA based medicine's agency application for EXPovio approval based on the BOSTON study population shortly after we have the definitive decision from CHMP or EMA.
And we'll update, for sure when we learn more. I'll turn it over to Mike Mason, just comment on the launch in Europe and the plans in Europe? Sure. I mean,
we see
the real value in Europe from a, commercialization perspective really post, Boston approval. So we're certainly targeting being commercial ready whether on our own or with a partner. Like 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 Espilvio through October November? And, do you expect to provide preliminary unaudited 4Q numbers at JPM like you did last year?
Yes. I mean, I think at this stage, we're not really able to provide much detail on fourth quarter sales. I mean, that's clearly where there's still a few weeks left in the quarter. So, and we're focused obviously right now on the launch of BOSS We do expect to provide some additional guidance, at the JP Morgan Conference. We have a scheduled presentation, that's been confirmed for for January 11th.
And so I think that's probably more appropriate time to give an update there. Importantly though, and clearly, today's from the FDA will allow us to immediately provide access, to a significantly expanded patient population. And so as we move into the first quarter, that's obviously the key and most important payment 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 2nd line versus 3rd 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 reshuffling as far as how they're being used currently?
Yes. So I'll start and, John, I think The considerations you saw on Slide 12 are really relevant here. But as you suggest, patient physicians have developed their preferred sort of 1st line, 2nd line, 3rd line regimen. And then there are a lot of choices to make. One of the, 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.
So there is, there is a desire in myeloma as in most other cancers to switch mechanisms when moving from one line to the next. And certainly for patients who have relevant 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 image for a proteasome inhibitor and the DARZALEX would switch out for selling. It is the only single once a week regimen that, that be approved in that second line. And then for patients who received a transplant, either in 1st 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 2 major indications for the use in second line. There are 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 John now. To add to this.
Yes, thanks, Michael. We know from the market research and from the ad boards that physicians have in a green last 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 patient by patient basis as we talk to our HDP customers. And we know Expobia will be used some in second line, some in third line, depend on the sequence of drugs that they have.
The primary goal though is to make sure they receive this new backbone in Spovio before they're reexposed. To another PI, another imminent or another anti CD38.
Our next question comes from Eric Joseph with JP 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 All grade neutropenia relative to the Lancet publication, I'm seeing 48% versus 15% in the publication. What accounts for the discrepancy there?
And sort of to what extent does neutropenia, guide treatment, treatment selection in the earlier line. When choosing between options and the earlier line treatment, myeloma setting, thanks.
Yes, we're not sure we really understand the issue. I think it's a grade 3 versus grade 34 versus overall grade. We'll get back to you on that, Eric. But there's there was really no meaningful, difference. It's a lower rate of neutropenia in general.
In the BOSTON study. Again, even with the 3 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. And can you just reiterate the second question you had?
Well, just It's just related to whether the rate of neutropine that's showing here in the label is going to have an impact on treatment decisions when choosing between options.
I think for all cytopenias, 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 practices, grade 3, 4 neutropenia.
And in particular, rates of febrile neutropenia. We have extraordinarily low rates of febrile neutropenia. So even in patients who have Grade 34 disease, they have, primarily they receive G CSF. 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 causes 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 Veldex from a lot of the other combinations, with overall lower rate of opinion than many of them. But the clinically significant neutropenia grade 34, in particular, fibrosis and Trupania really are not part of our typical adverse effect profile.
Got it. Thanks for taking the
question and congrats again.
Yes,
I can say from the label, we had a 12% grade 3, 4 risk of neutropenia. And that's, a very, 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 John, just thanks for highlighting the groups of patients at your target for SVD. Is there any way you could kind of rank those or kind of break out the number of patients that you could potentially address by going after those subgroups?
Yes, we, 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. And just going through the label, it seems that I may be wrong on this, but what 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?
Yes. Ironically, the most common, preexisting condition across both arms of the BOSTON study coming in was cataracts in over 2 thirds of the patients. And, for reasons that remain unclear, we did have an onset of We had a higher onset of late, late cataracts typically was without, typically after 24 weeks. As compared to, what we've seen previously. Part of this is because we're giving longer therapy.
But the cataracts in both arms, but in the XPD arm are treated with standard cataract surgery. And this is the most common surgery in these older folks. So we don't really understand the mechanism. It certainly was it led to 0 discontinuations. It actually led to a very tiny number of even dose modifications or misdosed 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, clinically, clinical associations with the phosphate decrease. I do, I will address, if you can, I will just go back to Eric's question? The difference in the label, and 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.
So 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. And 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. And that's why the Lancet paper has a lower number.
The grade 3, 4 events for both the Lambstead and the packages are differs slightly, but are essentially the same, consistent with the notion that doctors will, consider a grade 3 or 4 opinion to be an adverse event. So they reported both as a number and as well as an actual AD. I hope that clarifies that. Peter, did you have another one? I'm sorry.
Yes, just a quick question around, the emergence of BCMA therapies and 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?
Yes. I think the second part is easy. I mean, Xpobio so far has been effectively combined, with at least MCA MCCN guideline support and publication support with all of the other major anti myeloma drugs to date. And we know that these combinations are in use. So We will be looking at the combination with Blend Rep.
We're aware of a couple of patients who appear to be receiving the combination already. Who have highly refractory myeloma. But our focus really now is on the Boston population, which is second line and later, as the XPD regimen on label. And then of course, as doctors choose to follow the MCCN and other guidelines, to go further. Whether BlendRep is a good drug, it acts well.
I want to be clear that the ocular events that are seeing with Xpovia, which are cataracts, are not the same at all, the keratitis that's seen with blood wrap. I don't think that this will preclude the combination. And I think history in 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, GlenRep included.
Our next question comes from Ed White with H. C. Wainwright. Please go ahead.
Good afternoon. Thanks for taking my questions and congratulations. So thinking about your market research, I'm just curious as to what you're seeing, for Velcade use in the second and third line, And the docs you talked 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. And then the follow-up is just what you're expecting to see, the impact on, EXPLOVIO use in the Pentive 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 1st 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. And it is used prevalently. So I don't know that willing the use of once weekly Velcade in the second and third line, but we do believe that selinexor because of the new mechanism, because it doesn't not affected by renal dysfunction.
It is active in high risk cytogenetics and so on, provide some really important and potentially very meaningful benefits to patients. And the last point to really hammer home, and we're talking physicians all the time, and this was seen in our advisory boards, is that the clinical data that came out of Boston are directly relevant to their clinical practice. This is the 1st 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, 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 LK down by 40%. The other thing we've learned to answer the second part of your question don't have a lot of great data on retreatment of selinexor, but the previous view and the emerging view for for Velcade and even Image and that more recently for DARZALEX or at least CD38 antibodies is that somewhere between 6 12 month hiatus for the reuse of drugs tends to allow for the tumors to reacquire sensitivity to those mechanisms So we wouldn't expect anything different, regarding selinexor at this point.
And we think that retreatment with expovial based regimens could happen late in later lines. And we would generally say that based on history, some kind of a hiatus, since the last time they received the Xpovio would be warranted, but we don't have data yet, to directly support that.
Great. Thank you.
Our next question comes from Arlinda Lee with Canaccord. Please go ahead.
Hi, guys. Congratulations on the early approval. I had a couple of questions about, maybe I know you guys are not promoting or did not approve. Off label. But I think in some of your earlier earnings slides, you had indicated things that would have subjected that you were getting off label use Do you think you can provide updates on that information and maybe another way?
Can you talk about what the durability is on commercial drugs currently? And then 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 and then I'll turn it over to Ian and John. I think when we get into the off label discussion, we should just be clear that there's 2 aspects One is the place in someone's therapy, in therapeutic journey that they get, exposure or any other drug. The pentor refractory label could come in as early as 3rd line therapy and can come on anytime later provided they receive the 5 drugs that are on label. Generally physicians and payers are okay with whatever cocktail is used in a line provided it is on it is on it is for the patients that are on label. And as you're correct, we have said that a significant minority of patients had received triplet therapy in the penta refractory setting.
And this was reimbursed very, very well across the country because it was applying to the patients who were in this penta refractory group. So there's a distinguish important to distinguish between the patient population and exactly what combination therapy they get. Typically, payers, have have left it up to the doctor, thankfully, to make those decisions to optimize therapy for the patient. And Yes,
maybe just a couple of points. In terms of future earnings, presentations. I think we'll have to wait and see. I mean, certainly, there is as you know, this is a competitive space with a number of branded drugs that, that we're now directly competing with. So I think what the types of commercial data that we show may or may not change, I think time will tell.
So I don't want to sort of promise anything in terms of what future slides might look like. In terms of the durability, and then maybe I'll let John 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 of months of drug per patient within our specialty pharmacy network. And it was approaching 3 months. And so that's consistent with what we saw in the STORN study, which was an average about 3 months of treatment. I think now what you're going to hopefully, what you will see is as this drug moves in combination with Cortezomib and moves earlier, into earlier line therapy, as Michael noted in the slide presentation, the average duration of treatment in Boston was 10 months compared to 3 months, in storm, we would expect to see the, the durability, 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. But it's certainly our expectation that the average duration of therapy increases. I don't know, John, if you want to comment on those, Ash?
And thank you, Just to further address the comment on current use in the market. And then post ASH, as Michael mentioned, most of our uses in the Pintra refractory setting today, most of that is 4th line bus. 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 Xfinity and be able to promote that in the 2nd, 3rd line setting where the size of the patient population is roughly six times the size of our prior indication. So much bigger opportunity to help patients. And 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 already and excited for the XPD 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 Kaufman, CEO, for any closing remarks.
Thanks very much. I'm just close with saying that this is a great day for patients and their families and their physicians and other health care providers. For the patients with myeloma, a tough, 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. And I wish everybody happy holidays, and thank you again for joining us today.
Have a great day.
The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.