Good afternoon. My name is Dylan, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Cary Form Therapeutics Phase III BOSTON Study Results 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 now like to turn the call over to Mr. Ian Karp, Karyopharm's vice president, investor and public relations. Please go ahead.
Great. Thanks. And thank you all for joining us on today's conference call to discuss the results from the Phase III BOSTON study presented this morning at ASCO 2020. This is Ian Karp, and I'm joined today by Doctor. Michael Kaufman, Chief Executive Officer Doctor.
Jaden Shaw, Chief Medical Officer and Mr. John Demiree, Chief Commercial Officer. On the call today, Doctor. Kaufman will provide some general thoughts about the Phase III BOSTON trial results. And then Doctor.
Shaw will review the key findings from the study, which are presented for the very first time this morning at the ASCO 2020 virtual scientific program. We will then ask our distinguished guests and my moment expert, Doctor. Paul Richardson, the clinical program leader and director of clinical research Jerome Oliver, multiple myeloma center at the Dana Farward Cancer Institute and the RJ Korman Professor of Medicine And Harvard Medical School to provide his thoughts regarding the clinical significance of these study results. We will then open up the call to answer some of your questions. Yesterday afternoon, we issued a press release detailing the results from the BOSTON Phase III study.
This release as well as an accompanying slide presentation are available on our website at carrierform.com. Before we begin our formal comments, I'll remind those following along in the slide presentation, which is on Slide 3, The various remarks we will make today constitute forward looking statements for purposes of the Safe Harbor provisions under this Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical development and regulatory matters and timeline, potential success for our products and product candidates including our expectations relating to the commercialization of Xpobio, financial projections and plans and prospects. Actual results may differ materially from those indicated by these forward 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 is on file with the SEC. And other filings that we may make with the SEC in the future.
Any forward looking statements represent our views as of today, but we may elect to update these forward looking statements at some point in the future, 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 and as of any date subsequent to today. With that, I'll now turn the call over to Doctor. Michael Kaufman, Chief Executive Officer.
Thank you, Ian, and good afternoon, everyone. I'm really thrilled to discuss the positive results from the Phase III BOSSA study. This is the 1st randomized Phase III trial to demonstrate clinically significant activity of once weekly exposure in combination with a current standard of care anti myeloma treatment in patients who previously received at least one prior therapy. We are tremendously excited about the results presented this morning at the ASCO annual meeting, and we believe that they could lead to a significant advancement in the second line treatment of patients with multiple myeloma as well as offer patients increased convenience relative to other commonly used currently used multiple myeloma treated regimens. While Xpovio in combination with dexamethasone received accelerated approval from the FDA in July 2019 for patients with heavily pre treated myeloma, The results from the BOSTON study demonstrate the benefit.
Xplovio may offer to patients earlier in their disease course and in combination with Velcade, one of the most commonly used anti myeloma drugs available, subject to obtaining future regulatory approvals based on these and other clinical data. And I'm pleased that just last week ahead of schedule, we submitted a supplemental new drug application to the FDA based on these data requesting an expansion of Expobio's currently approved indication. For those following along in the slide presentation, please now turn to Slide 4. Unfortunately, despite all the progress that's been made over the past 5 to 10 years, multiple myeloma remains an incurable disease where patients and physicians are in need of new therapeutic options. Myeloma is the 2nd most common form of blood cancer.
Approximately 32,000 new patients diagnosed each year nearly 130,000 U. S. Patients living with and battling the disease. And despite a number of highly active drugs available to patients, Approximately 13,000 people will die from this disease in 2020. I'd now like to ask you to move to slide number 5.
Or Doctor. Jaden Shah will detail the results from the BOSTA study. Jaden?
Excellent. Thank you, Michael. So Boston study was a randomized Phase III open label multicenter study designed to compare the efficacy, safety and certain health related quality of life parameters of once weekly SVD, which refers to selinexorplusdelicateindex smethasone, versus twice weekly VD or VELCADE indeximethasone alone. In adult patients with relapsed or refractory multiple myeloma, we received between 1 to 3 prior lines of therapy. Importantly, these dosing differences resulted in patients in the SVD arm receiving approximately 40% less Velcade and 25% less dexamethasone than in the BDR, and having about 35% fewer clinic visits for the 1st 6 months of treatment.
Boston study enrolled 402 patients and the primary endpoint of the study was progression free survival. Key secondary endpoints included overall survival, correction overall response rate, the rate of VGPR response that are better, overall survival and rates of peripheral neuropathy among others, which I'll discuss momentarily. Additionally, the BOSTON study allowed for patients on a VD control arm to cross over following objective progression of disease confirmed by an independent review committee. The study was conducted at over 150 clinical sites internationally from the U. S.
EU, India, and Australia. Were well balanced between the 2 treatment arms. Importantly, key patient characteristics that reflect what hematologists and oncologists see in the real world were well represented in the BOSTON study. For example, across both treatment arms, roughly 30% of patients had moderate renal impairment, Approximately 50% had high risk cytogenetics. And roughly, correction approximately 50% had high and approximately 80% had previously been treated with dulcade or Kyprolis and importantly, nearly 40% had been previously treated with lenalidomide.
Turning now to slide 7. You can see that the study met the primary endpoint with a significant improvement in progression free survival based on an independent review committee assessments. In addition, I would like to highlight and bring your attention PFS benefit as compared to twice weekly BD. You can see that the two lines in this PFS chart are separating the 1st few cycles of treatment and become wider over time. In fact, 10 patients on the VD arm had immediate disease progression as compared with only one patient on the SVD arm.
The median progression free survival in the SVD arm was 13.9 months compared to 9.46 months in the VD arm representing a 4.47 month increase in progression free survival and a 47% increase in median PFS. With a hazard ratio of 0.7 and a p value of 0.0075. Many patients in this study remained on SVD therapy for well over 1 year with some patients continuing on therapy for over 2 years. The average duration of treatment on SVD was 10 months at the time of the data based log, and this number is increasing with the patients currently continuing on therapy. When we look at the PFS data across key subgroups, the data look equally.
And in many cases, even more impressive, as can be seen on Slide 8. Now while the hazard ratio for the overall trial was 0.7, meaning SVD therapy resulted in a statistically significant 30% reduction in the risk of disease progression or death, the hazard ratio is even better across patient subgroups. This included the following: patients with 65 years or older, or those considered frail, patients with high risk cytogenetics and patients who had not been previously treated with a proteasome inhibitor, and patients who've been previously treated with lenalidomide. And because we often get questions from investors a tolerability profile of selinexor based on the previous storm study in patients with penta refractory disease, I want to emphasize that we think it's particularly noteworthy to the specific PFS benefit achieved with SVD in patients over the age of sixty five as well as in those patients who are considered frail. We believe these data further reinforce the potential utility of selinexor in this vulnerable patient populations, we're often prone to side effects from drug treatments.
As well as in patients with more standard risk. Now as we turn to Slide 9, can also see that SVD was associated with a significantly higher overall response rate across both the overall population as well as across various patient subgroups. The overall response rate for SVD was 76.4%, compared to 62.3% in the BD treatment group. And when looking at the difference in response rates between the two groups, the benefit of SVD was even greater relative to VD and some of the more difficult to treat patient subgroups including those with moderate renal impairment and those with high risk cytogenetics Please now turn to Slide 10. While of course the overall response rate is an important measure of a therapy's clinical activity, the depth and duration of each response can often be an even more important feature for patients and physicians.
In the BOSTON study, significantly more patients had a VGPR or a very good partial response or better on the SVD arm as compared to the patients on the VD arm. A reminder, VGPR refers to at least a 90% reduction in the patient's myeloma walk markers, while a complete response refers to 100% reduction. In the BOSTON study, 44.6 percent of patients on the SVDR achieved a VGR or better. As compared to 32.4 Similarly, 16.9% of patients on SVD achieved a CR or a stringent CR versus 10.6% of patients on the VD arm. Additionally, the median duration of response were also significantly higher on the SVD arm as compared to the VD arm.
The median duration of response on SVD was 20.3 months as compared to 12 Please now turn to Slide 11. Now while the survival data from the BOSTON study is still not final, The interim clinical data at the time of this analysis showed a trend toward an overall survival benefit associated with SVD. There were fewer deaths numerically reported on the SVD arm as compared to the VD arm. The median overall survival SVD has not been reached as of the data cutoff of February 18, 2020. However, we find this interim data quite encouraging for 2 major reasons.
First, approximately 50% of patients in the study had only received 1 prior line of therapy before entering this study, and so we're very early in their disease course. And secondly, the study included a crossover design, allowing patients who progressed on the VDR to cross over following disease progression. Therefore, we see this trend towards an overall survival benefit in the context that most of the patients on the BOSTON trial did receive selinexor at some point in their treatment. Final data on overall survival will be reported as data matures and becomes available. Please now turn to Slide 12.
Now as you may know, peripheral neuropathy is among the most common causes of treatment limitation and discontinuation of VD and combination VD regimens. I'm pleased to report that in the Boston study, the rate of peripheral neuropathy on the SVD arm was significantly lower than the rate in the BD control arm. Specifically, 32.3% as compared to 47.1%. Additionally, the rate of grade 2 or higher peripheral neuropathy, which was a pre specified secondary endpoint on the Boston trial, was significantly lower in the SVD arm. This is a particularly important feature of SVD therapy and one in which we believe will be well received by both patients and physicians alike.
Turning now to slide 1314, I'd like to highlight the most common treatment related adverse events in the SVD arm, which included cytopenias, along with gastrointestinal and constitutional symptoms. And although higher in general than the VDR, these were consistent with the AEs previously reported from other selinexor studies. Moves were manageable and reversible when dose modifications and standard supportive care. Additionally, when comparing in patients with more heavily pretreated disease, it's important to keep in mind that patients in the BOSTON study remain on selinexor treatment for an average of 10 months compared to only approximately In Boston, the most common non hematologic treatment related adverse events on the SVD arm for nausea, fatigue, decreased appetite, diarrhea and peripheral nausea, neuropathy, which were mostly Grade 1 and 2 events. The most common Grade 3 and Grade 4 treatment related adverse events were thrombocytopenia, anemia, and fatigue.
Importantly, while thrombocytopenia was common across both treatment arms, the rate of bleeding, especially grade 3 or higher, was very low in both treatment arms and seen in only 1% to 2% of patients. Peripheral neuropathy was the most common adverse event that led to treatment discontinuation across the entire study. However, as mentioned previously, the rate of peripheral neuropathy was significantly lower in the SVD group compared to the 17% on the SVD arm compared to 11% on a VD arm. To put this in a broader perspective, In our STORM study, the discontinuation rate of selinexor due to adverse events was 27%. In addition, from other Phase III myeloma studies in second and third line settings, 3 drug combinations often have similar discontinuation rates.
Furthermore, we have already seen from the commercial or the real world setting where Espogio is currently being prescribed With increasing experience, EXPovia can often be effectively managed with common supportive care measures and dose modifications and we're already seeing much lower discontinuation rates in the real world as compared to the storm study. Turning now to Slide 15. I'll summarize the Boston data presented at ASCO earlier this morning. First, Unlike most triplet therapies in myeloma, the SVD regimen represents a simplification of the Velcade based triplets for relapsed myeloma. With SVD, weekly oral selinexor replaces 1 of the twice weekly doses of Velcade.
Ultimately, this means fewer clinic visits, less overall Velcade use and reduced dexamethasone use. Well, with this added convenience and simplified dosing, we once weekly SVD significantly prolonged PFS, demonstrating median PFS improvement of 47% and significant increased overall response rates compared to twice weekly BD. This means that replacing the 2nd dose of Velcade with one dose of oral selinexor led to significantly prolonged PFS. SVD was superior to BD across key efficacy endpoints, including PFS, response rate, VGPR response rates and duration response, and across key subgroups including in patients over the age of sixty five, frail patients, those with prior lenalidomide therapy and those with high risk cytogenetics. Meeting OS has not been reached in patients with SVD versus a median overall survival of 25 months with BD.
In addition, once weekly dosing used in the SVDR was associated with significantly lower rates and severity in Velcade induced peripheral neuropathy compared with the twice weekly VD. And finally, adverse events associated with SVD were manageable and reverse alone. In summary, we're able to conclude from the BOSTON study that in patients with myeloma, we received 1 to 3 prior therapies including prior lenalidomide or proteasome inhibitor, once weekly SVD offers patients an effective, convenient triplet regimen requiring 35 percent fewer clinic visits and a reduced rate of peripheral neuropathy. Finally, as you know, the Boston study in part was conducted based on the encouraging earlier data we saw from Keriopharm stop. Phase 1btwo trial, evaluating EXPOVIO and low dose dexmedsone in combination with 1 of several approved standard approved myeloma therapies in patients with relapsedrefractory myeloma.
We continue to be very encouraged by the data from the additional arms of STOM study, which indicate additive or synergistic activity with EXPLOVIO, especially when you view the data in context with historical benchmarks. And the summary of this data can be seen in Slide 16. For example, In the EXPOVIO plus Kyprolis and dexamethasone or SKD arm of the STOMF trial, we saw an overall response rate of 71% which compares to an overall response rate of 23% in the benchmark study of controls index, methadone alone. Additionally, in the exposures plus pomalidomide and dexamethasone or SPD arm, we saw a 56% overall response rate and a 12.2 month median PFS, which compares quite favorably to an overall response rate of 29% in the PFS of 3.6 months in the benchmark pomalidomide plus dexamethasone Phase III study. While of course, there are many limitations when trying to compare data across different clinical trials, the stop data provide strong rationale for further clinical investigation of selinexor in combination with standard approved therapies beyond just Velcade.
Please now turn to Slide 17, where I'll highlight our key steps following today's exciting announcement. First, as we announced last week, we've already submitted an sNDA requesting an expansion of the current exposure label. We'll continue to support the FDA's review of this application and hope to bring Xplovir to an increasing number of patients as quickly as possible. Next, we'll continue to work with the EMA as we review our current MAA based largely on data from the STORM study, with a hope of receiving a decision later this year and plan to submit the Boston data and a formal MAA later this year. And finally, depending on the FDA review time and outcome, we expect to commence the U.
S. Commercial launch of Xpovio in the population studied in Boston before the end of 2020 or early 2021, with our existing commercial infrastructure in the U. S. Based sales force. With that said, let me take this opportunity before Doctor.
Richardson says a few words to offer my very sincere appreciation to all the patients. Their families, physicians, caregivers, advocacy organizations, our current carry form employees and investors in our company who have helped us get to this monumental day. There's no way we could have gotten here without all of your dedication and persistence. And for that, we're immensely thankful. At this point, I'd like to ask Doctor.
Richardson, a world renowned myeloma expert, who has been a leader in the clinical development of many of the myeloma drugs used today, including vortizmig, lenalidomide, pomalidomide and selinexor, among others, to provide some of his thoughts about the current treatment paradigm and how the Boston data might impact future treatment options for patients. Doctor. Richardson is a clinical program leader and Director of Clinical Research at the Jerome Lippert multiple myeloma center, Dana Farber Cancer Shoot, is also the R. J. Korman, Professor of Medicine at Harvard Medical School.
I'll also remind you that Doctor. Richardson is not an employee of Care Firm, adviews and statements he will make on today's calls are as owned and specifically those not specifically those of Karyopharm. With that, Doctor. Richardson.
Thank you, Jatin. That's very kind of you. It's a pleasure to join you and Mike and the team on this this afternoon's call. And it's wonderful to be part of the Boston study and in particular to see the success of Boston after the success obviously of storm, but some of the questions that storm left I think are being really addressed beautifully by the results from Boston as you so nicely outlined. And I'm very happy to discuss some of those conclusions and in my opinion, the very positive results, particularly regarding tolerability and some of the relevance of real world data that this generates in my view.
But more above all the impressive results both in the population overall, but also in particular in the high risk patients. But we've certainly come back to that What I wanted to do first of all for the audience was just sort of give some background on the treatment of multiple myeloma and recognize that obviously we've made tremendous progress in the last 2 decades against this, and we still unfortunately hear the 2 incurable hematologic cancer But having said that, with the advent of critical classes of drugs, and I'm on slide 19 just for everyone, you can see here that back phone agents such as bortezomib and coterzomib have really provided important advances in this space. I do want to add to this exacerbib, which obviously has an improved role and has provided a very well tolerated approach with proteasome inhibition. It's important to note particularly, given the oral approach, which I, in my opinion, increasingly matters as we live in the post an ongoing COVID era. In terms of the immunomodulatory drugs, we've obviously got a host of opportunities there offered through first thalidomide, but now lenalidomide and pomalidomide And obviously there are some exciting new agents on the horizon in the form of the cell mods as well.
We have monoclonal antibodies and specifically, of course, daratumumab and iliutuzumab and the recent approval of isatuximab, I think, adds nicely to that platform and we have some exciting new antibodies on the horizon. Now I think in the context of selinexor, what's so exciting to me personally is that it's an entirely novel mechanism of action and this targeting of the nuclear export proteins XPO-one which is so central to myeloma pathobiology, I think is really important to appreciate. And this novel mechanism of action, in my mind, is an essential component of what we're trying to achieve in myeloma, which is to bring together a veritable sort of army navy Air Force Marines all the assets that we can to bring the disease under control. Now I think it's important to recognize that in the context of real world practice, and the ability to use backbone agents and combine them does actually generate some important concepts that we need to get ahead around And I think the point we're making here about drugs with proven single agent clinical activity are generally preferred by clinicians is probably self evident, I would suggest to most people on the audience, but the critical thing to recognize is that by using these backbone approaches typically with an immunomod later and a proteasome inhibitor.
And we'll hear some very important data in that regard actually over the weekend at this meeting at the ASCO meeting I'm referring to, of course, But in that context, it's very important to recognize additional combination strategies that are incredibly relevant. Obviously, with the introduction of the antibodies, and now of course, with the impact of selinexor and as so nicely illustrated with the results of Boston. Now when we think about the constructs of bortezimib, I think we would need to realize that this is a clearly well established drug. It's really a 1st in class. And obviously, I'm buying bio I was very fortunate and privileged in fact to be part of the development team on the clinical side for bortezimib.
So bortezimib is very near and dear to my heart. But having said that, at a more practical level, especially in the real world of what we're facing now, it's a very good dance partner. It's a very cheap a drug relatively speaking now with its generic status. And I think what's so exciting about weekly autism, particularly combined with other strategies is that it makes great sense in the context of the COVID era as we try to minimize visits from patients to the clinic And at the same time, we want effective regimens that are practical, cost effective and useful. I want to use that last term carefully because that's obviously a complicated topic, but certainly as a partner with other drugs, it makes great sense as a true backbone.
Now we do know that bortezomib classically is dosed twice per week and subcutaneously now has made a big advance in terms of peripheral neuropathy But what's also very important to recognize is that by going to a weekly schedule, and this has obviously not only improved tolerability dramatically, but also convenience as well underpinning it. And again, the results from Boston, I think, echo in that context. So as I move to Slide 20. I really wanted to sort of bring that out by comparing for you a variety of large Phase III trials. And of course, you've heard so nicely from Jatin about Boston, and obviously Doctor.
Demopulos presented beautifully the results this morning. What you can see here, of course, is that its comparability to other regimens, certainly in terms of efficacy is an the natural partner in terms of what you see for Boston versus, for example, Panorama 1 and for that matter, for optimism, which is a study that we published recently and has provided a very real world platform. Clearly, the combination of daratumumab and tesumib and dexamethasone in the CAFTA study stands out as being particularly active. But I think it's very important to realize in the real world as daratumumab is used increasingly upfront in the treatment of myeloma, the implications that that has. I think also as we think about response rates across the respective studies, you can see here again that the Boston data actually are very comparable, and that also applies importantly to high quality response.
Now what I'm also particularly, I think is important as we translate these findings from a phase 3 carefully controlled clinical trial to real world practice is something that Jatin spent some time on and very appropriately, which is this whole construct around tolerability. And as you can see here, and whilst we do see some magnification of hematologic toxicity say, for example, for thrombocytopenia compared to optimism. Nonetheless, if you compare it to Casa or for that matter to the Panorama study from some years ago, you can see that the results are very comparable, particularly when it comes to thrombocytopenia, but also interestingly it performs well in terms of neutropenia. Now what does stand out are some of the GI toxicities that Jatin talked about. I want to stress that these are manageable with appropriate supportive care, but no doubt There's no question.
They are challenging, but they are manageable. And particularly in community practice, I've had many of my colleagues in the community stress that obviously they're very comfortable managing antiemetic therapy in the context of other regimens for different malignancies such as colorectal disease And so in this context, there's a matter of practical application with a proactive approach to anti amesis and GI management and certainly my own clinical experience. In combination strategies. This is not an Achilles heel in my view, to the combination of bortezomib and selinexor far from it. And in fact, we're very pleased with how it's been performing in that context, particularly with the selinexor administered on a weekly basis.
Now I think what's really attractive about the Boston data is the peripheral neuropathy signal. And that stands out. And as we compare, for example, Boston to Casa, to Panorama and indeed to optimism. You can see that in this context peripheral neuropathy obviously is performing well compared to the comparators. And this I think is attractive.
So in a nutshell, I think it's important to recognize that there's twice weekly dosing of this control arm in the BOSTON trial has matched to these other studies. It's very consistent, but what's also particularly striking is that in the 3 drug arm of the BOSTON study, combined with selinexor, the tolerability profile is looking, I think, encouraging. And so with that in mind, I'd now like to focus on questions and answers because you've heard a lot from Jatin and hopefully the information I've provided is also helpful to provide context So, Jack, and if I may, I'm going to move to slide 21, which is to focus on questions and answers.
Great. So, we can open operator. You can open up call up to, to questions, please.
Thank I show our first question comes from the line of Brian Abrahams from RBC Capital Markets. Please go ahead.
Hey guys, thanks for taking my questions and congratulations on the detailed data. First question for me, I guess maybe more for Doctor. Richardson, if you look at the overall survival curves, it looks like maybe there's a hit some hints of a trend here for patients who start on the selinexor arm versus crossing over. And then the subgroup analysis suggests that this drug, this regimen may work better in patients in which this is the first their first PI exposure within this combo. So I'm just curious looking at those two pieces of data.
How does this influence how you might think about how early to use selinexor within the treatment paradigm and how do you sort of balance some of those efficacy attributes versus some of the tolerability characteristics that you mentioned? And then I had a follow-up for the company.
Yes. No, that's a great question and thank you for it. It's a very important point because whilst we're making tremendous inroads against standard risk myeloma. And we've got this wonderful, median survivals that are now in figures that we could never have anticipated before. There is this real challenge of high risk disease early.
That's a real problem. It tends to be 17p enriched and highly resistant. And I think that that's why I personally in this study was so pleased with the performance in the group with deletion 17p. As one example. So clearly in high risk disease moving it earlier makes great sense.
And I agree with you entirely when it's partnering for the first time, with a proteasome inhibitor, the performance in that group is particularly impressive. So as you think it through, it's logical to me that this would break its way up into the upfront setting, particularly in high risk disease. I think honestly that would not be restrictive then. And I think particularly now that some of the tolerability concerns that I think people legitimately had based upon the storm data have been far more reassured by these data where you can show in the context of prospective randomized multicenter international trial a managed the fact that the side effect profile is manageable is particularly important. So I agree with you.
I think moving earlier is going to become a next priority. What is clear is that in my opinion is that waiting to use selinexor later in the disease may actually be entirely the wrong thing to do based upon some of these information here. And I agree with you also that the fact that the overall survival signal is coming through so early is actually, that's particularly striking. As you may appreciate, that's obviously not what we all we see in necessarily other Phase 3s in this setting.
Great. And then just follow-up then maybe for the company on the safety side. I guess when you look at the differences in the overall adverse events, it looks like there's maybe some imbalances in the GI tolerability and in cataracts as well. I guess for the latter, I'm just wondering to what degree this might just represent the fact that patients are progressing or that the time to progression is longer. So they're on steroids for a longer period of time and maybe some of these adverse events imbalances might just be a function of how much time people are on patients are on each regimen prior to crossover.
So curious if you've done any analyses sort of normalizing these AE rates for exposure to the arm that patients were randomized to and whether you might expect any opt to monitor requirements for patients going forward? Thanks.
Jaden, do you want to take that?
Yes, absolutely. So I think you make a good point there with the cataracts. I think the what we've seen with the onset of cataracts, you're right, it's going to be multifactorial in terms of the reasons why our older patients get cataracts and part of it is driven by the long term steroid exposure. But there is this increased cataract risk that we see on the combination with SVD again. When we look at the time to onset of cataracts in the SVD arm, these patients is not an acute event.
This occurs after about 7 months on therapy. And so it's after really prolonged therapy and exposure to this combination therapy. And in fact, these are very clinically manageable. When patients have it, there's not any additional ophthalmological requirements or evaluations. This is really standard management.
So if you have cataracts, and seen by an ophthalmologist and as a worsened clinically, then you make the clinical judgment for when you need cataract surgery. These patients can go on have cataract surgery and then get back on therapy, with continued treatment. So I think there's to your question, it's typically seen on the delayed onset. Multiple factors can impact, the cataracts and they can be managed with standard kind of cataract surgery. With no additional ophthalmological evaluations or examinations or monitoring needed.
Thank you.
Thank you. On a
quick addendum to that, there's a quick addendum to that There were no discontinuations due to cataracts, which just reiterates what Jaden said, that this is very manageable. And actually 2 thirds of the patients across the trial came in with a history of cataracts and or cataract surgery. So this was actually the most common medical history across the entire trial, which just stresses this is very common event. And essentially most of these patients, particularly with myeloma and the Dex someethasone exposure will develop that.
Yes. I agree, Mike. And if I may, I just want to add to that from a sort of a practice perspective. The whole to me, the other major advantage of the experimental arm in the Boston study was the fact you were relatively dext bearing with the 3 drugs compared to the 2. So our impression from this was that was extremely helpful.
So I agree with you entirely, Mike. It's a problem we face. We have an elderly population period patients have had a significant period on trial steroid exposure. And so they're a set up for this issue, but the fact that this is actually a relatively steroid sparing regimen is an important positive. Thank
you. Next question? Thank
you. Our next question comes from the line of Peter Lawson from Barclays. Peter, if you have your line on mute, please unmute yourself.
Thanks. Thank you. So, Doctor. Richardson, just on the change in landscape we're seeing for 1st, 2nd, 3rd line treatment. And also drugs moving earlier line, do you think the current trial, it would make it clear where to use you selling in the treatment paradigm?
Oh, I think it definitely provides the highest level of evidence for using it earlier. And I think this Phase III trial, let me speak for example to the NCCN, this will get a category 1A designation based upon this. And that's important from an insurance point of view in the U. S. Space.
And I think it provides a great impetus to moving earlier in the European regulatory space as well. So I think in first relapse, but as a fellow Brit, you'll appreciate what that means perhaps in the United Kingdom will be an interesting one. But I hope for example, it will provide the same sort of platform that was provided by Panabinostatin Bortezomib in the UK paradigm, for example, where the way in the United Kingdom of panobinostatin Bortezomib is used in an is in early relapse based upon the panorama data I would argue that the justification for Boston moving Sally and Bortezanib early into a treatment paradigm and even as a difficult a space as the UK environment is very much supported by the results of Boston.
And then just on PFS and hazard ratios, how should we think about that for the 3rd line patients? How did they or is there any color you can give in sense of how they feared versus 1st line and second line patients?
I think you absolutely when you look at the forest plots, I find that slide that Jatin showed really informative. I think got obviously the striking benefit in first relapse. That's very typical of what we see actually in phase 3s of this design. Obviously, the PI naive patients did particularly well, but that's not surprising, but that's important in the groups of patients, for example, who are now receiving an image based initial treatment with an antibody, but are not necessarily exposed to a PI early. That's an increasingly large group with the success of the MAIA trial and other such approaches.
So important positive for the study in that regard. And then as I mentioned before, the high risk group are particularly impressive, but I think JADA made a very important point that if you look at patients who are actually over the age of sixty five, that was a very important positive from the trial. Mean some SYNNEX would have argued that's a surprise. And I would understand why they would say that, but that's actually a group in which we saw significant benefits. So So I think again, these forest plots are very helpful in making sense of that of your question.
And did we get any color around the 3rd line patients? I'm just trying to work out if it's kind of driven by 1st and second line patients how the underlying patients may have done?
Well, the analysis that you saw on the forest pot is for 2 to 3 for 204 folks. I would argue that the 3rd line group are probably, and I'd want Jackson to give full numbers on this for you. But certainly from my perspective, third line patients to whom you would have equipoise exposing to Bortezimib and dexamethasone as a doublet versus SVD is triple that that I would imagine is a minority of patients in this trial. And Chatin, perhaps you can comment on that.
No, and I think, obviously, Paul, what we see with the patients from 1 to 1 line versus 2 to 3 lines, we see really preserved hazard ratio there. And so we see activity that we would expect to see, if it's 1st or second or third, Obviously, when we look at patients with that, prior PI therapies and really supports needing it in the first relapse setting where we see those patients who are Velcade. Now you've had really the most dramatic benefit, supports that.
Right. And I can add to that by giving you kind of real world experience from since the approval of storm. We've used frankly selinexor in combination as our approach. And typically in that regard, we've either combined it with selinexor and carfilzomib, we'll combine it with selinexor and bortezomib and our other approach has been with Pomeralidomide actually. And that's kind of where in the 3rd line you might be with Sally, but that is in fact been an attractive approach in those settings because of the stop data supporting that.
So that's kind of how we've approached it. This would now allow us to move earlier with the Sally for short.
Our next question comes from the line of Maury Raycroft from Jefferies. Please go ahead.
Hi, everyone. Congrats on the update and thanks for taking my questions. First one, I guess for the management team for Doctor. Richardson too, Just wondering if you could talk more about potentially quantify dose reductions and interruptions and how those influenced SVD Sbd efficacy and how this informs real world practice.
Jaden, maybe you can comment on that?
Yeah, absolutely. So I think, when we look at the dose reductions, there's going to be the anticipated dose reduction that we'll see with Mortisement. When it comes to selinexor, the patients who do have a dose reduction typically will have 1 dose reduction. So when we look at the median dose intensity, for those patients who have dose reduction will be 80 milligrams once a week. So we typically see that those patients who do need a dose reduction will 80 milligrams once a week from 100 milligrams.
And that has been, I think, the dose of most of the patients who need a dose reduction will do. So it's, And we get all the side effects that we see are dosed and schedule dependent. And so those can be remunerated, and we see that with the single dose reductions. So it's not necessarily a difficult transition to identify the right dose for that patient.
Yes. And just to add, from best we can tell, there's very little effect of the dose reduction on the continued efficacy. All the patients in this said start at $100,000,000. And it's a little bit like Revlimid in that regard where you start at $25,000,000 and you keep going down as you need to with neutropenia usually. We go down and we maintain these responses for a very long time, as you saw with the DOR in the 20 month range.
Sorry, sorry, Justin, I beg your pardon. I was just going to echo those two comments very quickly because that's we're very comfortable with that as a treatment approach you find best dose and over time less is more. But at the same time, that's a paradigm that's very, very practical and something we do frequently So sorry, Jackson, please carry on.
Got it. Thank you. And then, for the patients that progress and crossover to the SPD arm, can you say what the overall response rate or DCR rate was for those patients? And as OS matures, will you continue to send those updates to FDA?
Yes, I'll take that. We don't have the data completed yet for the crossover. We know those patients do stay on, we have had bona fide responses in them, even though they're patients who have disease that's immediately refractory to Velcade. And we will, to answer your second question, we will absolutely, and we always do have periodic safety updates to the FDA. Which includes overall survival.
Next question please. Thank
you. Our next question comes from the line of Jonathan Chang from SVB Leerink. Please go ahead.
Hi guys. Thanks for taking my questions. First question, just in reference to something that Doctor. Richardson mentioned earlier, In terms of the initial launch of Xpovio, can you provide any color on how much of the utilization is already in the Boston or some other triplets setting versus the storm setting?
Paul, you can start. And then, John, We'll take it over.
Yes, I'm very happy to do that. I mean, obviously, we've used it per label. I want to be careful about this because certainly don't want to imply that we run around prescribing off label all the time. But my point is that it has been prescribed per label and we then having our own practice and certainly speaking to my own, I've combined it and I would say I've actually gone more in that direction than I have as truly on label per the relapsed refractory approval. But I would stress that that's very much a practice pattern that most especially in the myeloma expert space and considered a relatively experience in that regard.
That's what we kind of do. In community practice, it may be a little bit less so and then maybe more literal to the label. But I think once the stop data became more widely appreciated and particular after Christina Chen's presentation of pomalidomide and selinexor at ASH with some very positive comments generated thereafter by thought leaders in the field such as my colleague Vince and Raj Kumar who have been previously rather but much more cautious with selinex or Basically, I think the combination approaches have gathered garnered increasing popularity, but I want to be careful about that because that's just my impression. But I would hand to Jack in to comment further.
Katie over to John, our Head of Commercial, Jason, first.
Yeah, of course. Of course.
I think Doctor. Richardson framed it very well. From what we've heard in AdWords, a number of the leading advisors, a number of the leading academics, have tried the drug in the triplet setting or the multiple combination setting. So what we see for the most part is still majority of usage is still on label in this farm based population as exfolioblast ex amounts done at this point.
Got it. Thank you. And just second question, can you talk about next steps for expovial multiple myeloma development? In other combination settings given the data that's been generated already in the STOMP study?
Yes. Hi. I'll take that quickly. We have a number of combinations ongoing that are continuing within stomp and then we are planning, on a Phase 2 or 3 study of selinexorpalmdex versuspalmdex. As a randomized study, this would be an all oral triplet versus an oral doublet, and we're working with, regulators to design that study.
We're hoping that that study will be occurring in the upcoming within the bytheendoftheyear or early next year, just given all the other things that we have going on, We have we're accumulating additional data in combination with Daratumumab with Kyprolis. And with Kyprolis, I would emphasize, particularly in the very late stage in patients with extra medullary disease. We've had some pretty intriguing results as well as after CAR T relapses. So that's an area there. And then our intention is as newer agents are approved, we believe that given the mechanism of action, which is as a tumor suppressor activator, but also, given the fact that we can administered this drug orally once a week that selinexor represents a really optimal or potentially optimal partner for these other drugs.
And we intend to combine pretty much with any other agent available in myeloma.
Our next question comes from Eric Joseph from JP Morgan. Please go ahead.
Hey guys, thanks for taking the questions. Just a couple for me to first on peripheral neuropathy. And I'm wondering whether there's any trend as to where the benefit was strongest. Perhaps depending on whether a patient's stock prior or any other baseline characteristic? And then for Doctor.
Richard, I'm curious to know sort of to what extent a patient's presence rating, but is currently collecting you know, they might see NSA or Greg,
you're breaking up. Eric, maybe I'll give you a minute. Maybe we'll answer the first question and then you'll answer as the second one. Hopefully, your internet comes back. Jaden, Can you give any insight on the PN?
Yes. Your specific question, is there any subset of patients that less or more peripheral neuropathy. And so we have not done that analysis. And so broadly speaking, one of the key points on this whole peripheral neuropathy issue is that Anytime we have any triplets, we see increases in rate of peripheral neuropathy compared to the control arm or BD. And this is one of the first triplets This is the first and only triplet that actually shows reductions in peripheral neuropathy with better outcomes.
And this is significantly important because these are patients getting real lines of therapy with these combinations that neuropathy can be lifelong or, and so it caused significant long term morbidity So this is, I think, an important issue for both patients and caregivers. But from, I think, practically speaking in context, when we look at other triplets, in fact, this is a lower peripheral we see with other triplets, when you add on to VELCADE based regimen.
Right. And I would add to that with the following sort of scientific observation that We've been very struck that Bortezomib neuropathy is a complicated entity and there are multiple approaches to abrogating, which are particularly important now given that there are different toxicities from different classes of proteasome inhibitor that are becoming much more importance we think about where we are now in terms of a real world practice. And I'm speaking specifically in the COVID era, and how we've got to be very careful about toxicities that are vascular. So this makes it very, very important for us to think proactively about neuropathy and say, okay, neuropathy has been a big problem and it's why, typically, I mean, personally, I mean, coughllism has been a fabulous PI. It's a great addition to the armamentarium.
Personally, it tends to be my second choice. I think the reality is that in practice now with some of these differential toxicities beginning to matter, managing peripheral neuropathy is going to be very important. So the fact that we're seeing a lower rate with approaches in a value add in my opinion and the mechanism behind it's intriguing. I think an anti inflammatory effect may be very relevant We've made this observation previously with other approaches such as partnering steroids appropriately with budesonib to minimize neurotoxicity And I'm intrigued by the observation that we've seen from Sally, that it's not just simply the weekly schedule. It may be more than that.
And I think that's very important to remember.
Operator, I'm sorry. Unfortunately, we're coming up on the hour and I'm cognizant of everyone's time. I think we have time for just one more question. And I apologize for those still in the queue. This has been a great, great discussion and we're happy to follow-up separately.
So apologize in advance, maybe we'll just take one final question.
Our last question comes from the line of Alinda Lee from Canaccord. Please go ahead.
Hi guys. Thanks for squeezing me in. I had a couple of questions on, the GI talk cities. Are you curious about how much of the proactive management of these, went into the Boston trial? And then secondly, Doctor.
Richardson, I was, you had mentioned that this, you see this going earlier in lines of therapy. And I was wondering in particular, were there particular combinations that you were interested in? And if so, what would you like to see? Thank you.
So, Doctor. Jason, maybe I'll take the first one on the protocol and then over to Paul.
Yes, absolutely. So on the GI side effects, there's a protocol mandated Zofran or 5 HTN antagonist. And so that was effective we were finding in the, real world as folks use it commercially is oftentimes they'll use 2 anti medics, and that can be also effective as well. So the protocol mandated is single antiemetic.
And I
think you have to remember the side effects. Again, we're different than we see in storm when we use the 80 milligram twice a week, and the GI side effects were, you saw an increased number in severity at that dose. And so was a dose and schedule change to once weekly, that's also been significant improving the tolerability.
Oh yes, sorry. My pleasure. I would simply add to that that obviously in our practice, we're very comfortable using multiple anti medics as needed to improve tolerability and being proactive about them rather than reacting to nausea. Being proactive to headed off at the past. But building to the second question, which I thought was very good, and thank you, would be what platforms will we use?
Well, I think one of the obvious ones is we're establishing that PIs and Image are our backbone approaches in combination, and you hear some very important data this weekend from the plenary session in that spirit. And I think obviously we'd be looking to how to best partner, selling in that space. Frankly, we already know that Sally partners very well with image. We know that from the Stomp data and Christina Chan's presentation at ASH in December, And obviously now we have highest level data that it partners well with Cortezomib. So one could think about an image PI platform upfront being a logical place for Sally to move as a next step.
Right. Okay. Thank you. Thank you, everybody. Again, apologies for the short notice.
Just to summarize and close, Boston is the only Phase 3 study to our knowledge to evaluate a once weekly Velcade based regimen on the experimental All of the other Phase 3 studies utilize standard twice weekly to update on both experimental and control arms. And looking across the studies, as Paul did, in his discussion, provides an initial indication that once weekly Velcade may provide a desirable dosing regimen in combination the selinexor index. The efficacy and safety characteristics of the SPD regimen, with its simple once weekly dosing schema, leading to lower cumulative Velcade and dexamethasone dose may offer patients and physicians a novel and highly active approach to their recurrent myeloma. Particularly compared to the traditional BD dosing regimens, but twice weekly. And given the oral nature of selinexor and the once weekly regimen we think is particularly relevant in today's treatment landscape.
Thank you all very much, and we look forward to additional updates in the future. Have a great day.
Thanks very much everyone. Thank you.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.