Greetings, and welcome to Insight Corp. 3rd Quarter 2019 Financial Results Conference Call. At this time As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Mike Booth, Head of Investor Relations. Please go ahead.
Thank you, Brock. Good morning, and welcome to Incyte's third quarter 2019 earnings conference call and webcast. The slides used today are available for download on the Investors section of insight.com. I am joined on the call today by Urve, Barry, Steven, and Christiana, who will deliver our prepared remarks and by Dash who will join us for the Q And A session. During the question and answer session, I ask that you limit yourself to one question.
And if needed, one follow-up as this will enable as many of you to ask questions as time allows. Before we begin, however, I'd like to remind you that some of the statements made during the call today are forward looking statements, including statements regarding our expectations for 2019 guidance. The commercialization of our products and our development plans for the compounds in our pipeline as well as the development plans of our collaboration partners. These forward looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially. Including those described in our 10 Q for the quarter ended June 30, 2019, and from time to time in our other SEC documents.
We'll now begin the call with Herve.
Thank you, Mike, and good morning, everyone. Incyte continues to execute well across all aspects of the business. We have delivered multiple positive updates from our late stage portfolio in recent weeks, and our product and royalty revenues continue to grow at a remarkable rate for a company of our size. Product and royalty revenues in the third quarter grew at 24% over the same period last year, totaling over $530,000,000 and including $433,000,000 in Jakafi sales, which increased 25% in Q3. Sales of Iclusig in Europe as well as royalties from Jakavi and Olumiant also increased year over year.
At the beginning of 2019, we set out an ambitious list of R&D Gold for the year, and I am pleased to report today that we have already achieved the majority of them. The NDA for Pemigatinib seeking approval as a treatment for patients with FGFR2 driven cholangiocarcinoma has been submitted to the FDA. And the positive updated data that supported the submission we have presented in September at ESMO. We recently reported that reached to the phase 3 trial evaluating ruxolitinib in steroid refractory acute GvHD met its primary endpoint of superiority over best available therapy. This data further reinforced the efficacy of Jakafi as the standard of care treatment option for these patients, following FDA approval in this indication in May.
We were also pleased to provide 52 week follow-up data from our randomized Phase II trial of ruxolitinib cream in Vitiligo at of ROCSREEN experienced continuous improvement in their disease with additional time on therapy, and we have already launched a global Phase III program for ROCE stream in Vitiligo with results due in 2021. We still have some key items we expect to deliver before the end of the year, With for now, I'll turn the call over to Barry for an update on Jakafi.
Thank you, Irvin, and good morning, everyone. Net product revenues for Jakafi were very strong in the quarter, totaling $433,000,000. This is an increase of 25% when compared to the same period last year. Growth was primarily driven by patient demand which grew 18% year over year and there were no appreciable effects of inventory in the quarter. Because of the strong demand for Jakafi today, we are very pleased to be increasing both to a new range all three approved indications.
More than 50% of eligible myelofibrosis patients in the U. S. Are currently on Jakafi. And total patients on therapy increased approximately 5 see in this indication, especially in its 8th year since approval. Patient growth in polycythemia vera continues to be higher than myelofibrosis.
And within the eligible population, Jakafi has reached more than 20% penetration. We saw an opportunity to increase disease awareness in both PV patient and physician community and in an effort to augment the patient voice, we recently launched a pilot, television, and social media disease awareness campaign. This pilot was conducted in several key target markets where it has been very well received and we have now expanded the Education campaign nationwide. This is the 1st full quarter of sales since approval in steroid refractory acute GvHD. And while early, the launch is currently outpacing our internal expectations.
Importantly, we are seeing comprehensive access in both the inpatient and outpatient treatment settings and we continue to see strong uptake take and broad utilization across bone marrow transplant centers. I'll now turn the call over to Stephen for the clinical update.
Thanks, Barry, and good morning, everyone. Continuing with graft versus host disease, we were pleased to report the positive outcome for H2, the randomized trial of ruxolitinib versus best available therapy in steroid refractory acute graft versus host disease. We plan to share these data with the FDA for inclusion at an upcoming scientific meeting. Reach 3, the randomized trial evaluating ruxolitinib in patients with steroid refractory chronic graft versus host disease is ongoing and has almost completed recruitment. A recent interim efficacy and safety analysis conducted by an independent data monitoring committee recommended that Reach 3 should continue without modification with results expected in 2020.
Moving on to Pemigatinib for cholangiocarcinoma. Slide 11 shows the data that were presented at ESMO. In which formed the basis of our recent new drug application. As you can see, in cohort A, the overall response rate was 36%. Media progression free survival was 6.9 months and median overall survival was 21.1 months.
Importantly, the vast majority of patients have some degree of tumor size reduction as evidenced by the 82% disease control rate and as illustrated in the waterfall plot on Slide 11. We believe that Pemigatinib offers a meaningful over the current standard of care in the 2nd line, which typically results in single digit response rates, median progression free survival of 3 months have an overall survival of approximately 6 months. The most common adverse event of ore grades was hyperphosphatemia, which is an on target effect of FGFR inhibition that can be managed with a low phosphate diet, phosphate binders, and diuretics. HypPro phosphatemia occurred in 23 percent of patients, which was likely due to the treatment for hypophosphatemia. SERIS retinal detachment was seen in 4% of patients, which was mostly grade 1 or 2.
If you recall, the only potential period of therapy for cholangiocarcinoma surgery, but approximately 70% of patients are diagnosed with unresectable disease. So the need for new therapeutic options for these patients is clear. My third slide summarizes updated data from the randomized phase 2 trial of ruxolitinib cream in Vitiligo. Which represented a few weeks ago at EADV. These data showed continued improvement in repigmentation with additional time on therapy as objectively measured by Vassy scores.
For example, in patients dosed with 1.5% PID and followed for 52 weeks, the facial VASI 75 was achieved in 52% of patients, up from 30% of patients at 20 week. 24 weeks, sorry, and the facial vaccine 90 was achieved in 33% of patients, up from 12% at 24 weeks. The global Phase III program of ruxolitilip cream in patients with Vitiligo is already enrolling with a facial VASI 75 at 24 weeks being the primary endpoint and we expect the result to be available in 2021. With that, I'd like to turn the call over to Cristiano for financial update.
Thanks, Stephen, and good morning, everyone. The financial update this morning will include GAAP and non GAAP numbers. For a full reconciliation of GAAP to non GAAP, please refer to slides 1920 in the backup section of the deck and to the press release we issued this morning. Our third quarter results reflect continued strong growth with total product and royalty revenues of $534,000,000 representing an increase of 24 percent over the third quarter of 2018. This is comprised of $433,000,000 in Jakafi and $21,000,000 in Iclusig net product revenues, $58,000,000 in Jakavi royalties from Novartis, and $22,000,000 in Olumiant royalties from Lilly.
We also recognized $18,000,000 in contracts revenue under our collaboration agreement with ILab, resulting in total revenues for the quarter of $552,000,000. Our total costs and expenses for the quarter on a non GAAP basis of $365,000,000 decreased by 1% from the prior year on a non GAAP basis and change from the prior year period, reflecting our decision to reallocate capital from the co founding of baricitinib and the development of epocatostat to our other late stage development programs. SG and A expenses for the quarter was $90,000,000 on a non increase over the prior year quarter. Moving to our guidance for 2019. Given strong performance of Jakafi in the 1st 9 months of the year, we are increasing Jakafi full year guidance to a range of one point $5,000,000,000 to $1,680,000,000.
Our guidance for both R and D and SG and A remains the same as we continue to invest in our commercial operations and our clinical development portfolio, and we expect certain of these expenses to be more back end loaded into Q4 2019. I will now turn the call back to Herve.
Thank you, Christian. So our last slide reminds you of our progress to date in 2019 as well as the remaining key news flow events we expect during the year. These expectations include the NDA submission by Novartis for CAPmatinib in patients with MET exon 14 skipping mutations in non small cell lung cancer. Catmatinib is another development candidate discovered in inside laboratories and has the potential to be an important product in lung cancer. It was recently positioned in the Novartis 3rd quarter material as a key approval for them in 2020.
And for Insight, Catmatinib also has the potential to be a meaningful contributor to our top line with over 500,000,000 in potential milestone and 12% to 14% royalties on global net sales. We are also looking forward to having the result of the BRAVITAS-three zero one trial of Itacitinib in 1st line acute GvHD in house at the end of the year. Itacitinil has the potential to be another key contributor to near term revenue growth. With this strong execution across our late stage development programs, we are making significant progress towards our strategic goals of adding diverse to the top line and further accelerating revenue growth. And that concludes our prepared remarks, and we are now happy to take your questions.
Operator, please give your instructions and open the call
session.
The first question today comes from Salveen Richter of Goldman Sachs. Please go ahead.
Thanks for taking my questions. So with regard to the early uptake and feedback for Jakafi and GV What does that suggest for the trajectory here? And have there been any gating factors? And then a follow-up for Herve Given the progress of your pipelines in both oncology and IAI, how are you thinking about business development opportunities?
Sure Salveen. So GVHD, as I said, the uptake has been very good since the beginning. We think the opportunity for itacitinib is ultimately where the opportunities lies. Jakafi is giving patients benefit right now. We believe it'll give benefits in acute GvHD as we are now.
And then in the future for chronic GvHD, and we await the results of g privatized 301 for itacitinib and a potential worldwide for that drug.
So Salin, on the progress of the late stage fully, obviously, it's, I mean, you know, our strategic goal of diversification and growth. I mean, that's really what we are. Aiming at and obviously a lot of it is now starting to take place with Pemigatinib. We a little bit about CAPmatinib, which is not always the most, known of our pipeline products that Novartis has been licensed to Novartis. So we have, we are on a good track to to succeed on getting these products to market over the next few years.
At the same time, we are obviously looking at BD opportunities that would fit with our portfolio. We are mostly looking at oncology hematology type of type of assets And, you know, it's a continuous process where we are reviewing opportunities. And, we should we are expecting, we hope to be able to to gain some additional products to fuel the growth of the top line in the next few years.
Thank you.
The next question is from Mark Frum of Cowen and Company. Please go ahead.
Thanks for taking my questions. This is for Barry. In the prepared remarks, you mentioned that the awareness campaign NPV is you're having some success. Can you maybe define that a little bit better? Are you already seeing an uptick in sales within those regions or is it more qualitative measures?
And then what type of budget are we talking about now that you're expanding nationally in trying to broaden that success?
Well, the way we measure uptake, it's very early. As we said, we did it 5 key markets across the country first. And what we saw there was really the uptake in our in social media sites. For example, take action PV is what we direct patients to go to or healthcare professionals to go to to get more information. There's education materials there, materials that can download to track their symptoms.
And we saw spikes in those first five key regions. Now as we expanded across the nation, which only started October 1st. So we don't really have all that much, data yet, but it certainly has grown dramatically on those sites that we're sending patients to. And the budget nationwide is relatively small. This is a 32nd commercial.
We're placing it at time periods that we think patients will see it, but at the same time, don't cost a fortune. So it's not going to the Super Bowl, but it is, in fact, we think being very effective as an educational tool for patients and healthcare professionals.
Okay, great. And then maybe short follow-up on kind of the market dynamics for Jack's site. Maybe some comments on what the initial impacts of Fedratinib's launch that you may or may not seen yet?
Yes, I think it's early. We haven't really seen much of an impact yet. We know that Celgene is really positioning it as a second line agent just by their pricing strategy that they came out with. And then very particularly their marketing materials that we have seen are positioning as a second line drug. Maybe you also are aware that the only two clinical trials that they have ongoing now, a single arm trial and a phase 3 trial compared to best available therapy are both after Jakafi.
So clearly, they're conditioning positioning it for a second line drug and we haven't seen the impact yet on Jakafi and we're fully confident because we have long term follow-up data, 8 years of data, more than 50,000 patients treated in the United States with a drug the safety profile is there. And of course, an overall survival advantage that, that I don't think that, Fedratinib will ever be able to achieve particularly with the KAKARTA study because it was never followed up on.
Great. Thank you.
The next question is from Tyler Van Buren of Piper Jaffray. Please go ahead.
Hey guys, good morning. Great to see the solid results. On the quarter. Just had a couple of follow-up questions to Mark's line of questioning. As you look at Jakafi and MF and PV, can you give us an update on duration of treatment for both of those indications.
Also, as we think about long term, in terms of PV, could we see ultimate penetration of the patient population to reach that kind of that 50% level that we're seeing with MF. And perhaps just some updated thoughts on the long term guidance that you guys gave last year. I believe it was $2,500,000,000 to $3,000,000,000 by 20.27 if we see the continued growth in PV and GvHD that seems exceedingly achievable. So it would be be interested to hear your updated thoughts.
Sure, Tyler. This is Barry. We're still confident of the $2,500,000,000 to $3,000,000,000 long term guidance. So it's clear, as in terms of persistence, it's what we've said all along, to be honest with you. We have to turn to the clinical trials for persistence.
When you look at PV, when you look at this response data, you saw 80 plus 83% of the patients were still on therapy at 2 years. And in the comfort trial, you saw that 50% of the patients were still on at 3 years. So that's still our touch tone for for persistence. In PV, we continue to grow year over year. This year, we grew total patients in PV, 15% year over year and that continues to exceed the continued growth in patients in MF.
So we see that in PV, we'll catch up to the MF patients sooner or later. And we certainly are confident that the clinical profile of Jakafi and polycythemia vera patients could hit the 50% market at some point.
Thanks for taking the questions.
The next question is from Brian Abrahams of RBC. Please go ahead.
Strong quarter. On GBHD, can you provide any perspectives on the Reach 3 stopping rule at the interim and maybe frame expectations now that that readout been pushed out to next year. And related to that, I'm curious your latest views on the potential impact of JAK1 versus pan JAK inhibition on the potential for efficacy. In GVHD and the bar for it to sit in a readout now that you guys have more clinical and commercial experience in the space? Thanks.
Yes. Hi, it's Steven. So in terms of Reach 3, we don't normally guide to interim results but this time working with our partner in Novartis, we obviously did expect to potentially have some results by the end of 2019. As you can see, the study at interim made it through the interim analysis by the IDMC and they recommended to continue the study to completion without modification. The recruitment itself is about to finish.
We literally have only a few patients left. There's always a higher, by the nature of an interim, there's always a higher bar to achieve an interim analysis to close a study because you have to be very careful that you do it appropriately. So we're not at all worried. We remain extremely confident in the data sets. The primary endpoint in the chronic graft versus host disease studies and overall response rate at month 6, but there are numerous secondary endpoints that are important here.
Including failure free survival, symptom improvement, overall survival and others. So sometime in 2020, we'll get those results. We remain extremely confident in that. And as I just to reiterate, it was a little unusual for us to guide to an interim, but again, working with a partner, that what we did. In terms of, reading through to itacitinib and a more, Jack, one agent, a relatively more, hits JAK1 more than the other JAKs.
We saw our proof of concept data for atacitinib. It was strong across the spectrum of disease. But it was even stronger in steroid naive acute graft versus host disease, which is why, which led to gravitas-three zero one. In addition, patients with steroid naive acute graft versus host disease are immediately post bone marrow transplant or allogeneic transplant tend to be sicker, tend to have cytopenias, particularly low white cell counts and low platelets. So to have a relative JAK 2 sparing agent that doesn't cause as much cytopenia as the others is potentially beneficial from a therapeutic ratio point of view.
But in terms of the biology of the disease, it mediates the biology appropriately. And again, we remain confident in that.
The next question is from Michael Schmidt of Guggenheim. Please go ahead.
Hey, thanks for taking my questions. My just had a follow-up on GVHD as well. I think you said the launch is outpacing your internal expectations. Just wondering if you could help us with a little bit more information around what treatment share do you have at this point? And maybe what percentage of top line sales was contributed by GvHD?
Sure, Michael. Well, treatment share, I'm not exactly sure. I think that, we're the, most used agent maybe are already in the 2nd line setting, but I can't be sure if that trying to get information on GvHD is a little bit harder than MF and PV since it's all hospital used. So that's it. So I think last year, I said something like with spontaneous use and then with the approval, we'd hit somewhere around $80,000,000 for this year.
I think we're ahead of that, but I can't give you an exact the number for that, but we're very pleased with the uptake in GvHD. And we think with now the REACH2 data it'll even be stronger in the future.
Great. Thanks. And then maybe a bigger picture questions question for Hervea. So regarding the earlier stage, pipeline, I guess you're pursuing both new immunotherapies as well as targeted oncology drugs and obviously there's been some very interesting data generated in the last couple of years, specifically with TKIs going after driving including pemigatinib, obviously, but there are other targets as well. On the other hand, I think many would agree that the rate for new immuno oncology drugs has been rather mixed, I guess, in that context, I was just wondering how do you see your bigger picture pattern strategy evolve our longer term going after both areas.
Yes, I think, so thanks for the question because obviously it's very important and it's a field where the effect of the decisions we made over the past few years are always seen with the delay. So We were, obviously with a very heavy share of the research effort in immuno oncology and immunity in general, which led to a number of other projects beyond the beyond oncology. And what has been happening over the past 2 years is a rebalance where we have Now more targeted therapies or targeted,
I mean,
targeting oncogenic imitation type of projects that are a larger part of our portfolio. At the same time, we are keeping, immuno projects today. So it's a I would say it's a balance that is probably in the 60 40 or 40sixty kind of a kind of ratio where maybe in the past, it was more heavy on the immuno aspect. And, Dash, if you want to speak about it?
Yes, thanks for the question, Michael. Just to sort of echo what Avay was saying, I think you're right, at some level, the promise of immuno oncology is being tampered by clinical data. However, we still think there's plenty of opportunities out there in both the targeted and the immuno oncology space you'll remember, or you'll know from our, sort of access to modalities that we have both small molecule and biologics capabilities. So having both of those options open to us does keep the entire area open. And we have a number of programs that we think will enter the clinic in the coming months that target both going after a very traditional targeted therapeutic approach as well as the immuno approach and then combinations thereof.
The next question is from Cory Kasimov of JP Morgan. Please go ahead.
Hey, good morning guys. Thanks for taking my questions. First one for you is on expenses. So SG and A and R and D both came in pretty meaningfully below expectations for the quarter, but guidance was unchanged, which would imply a decent step up in 4Q just to get to the low end of your range. So is that something we should be anticipating and maybe to the extent willing to qualitatively comment on trends into 2020.
Do you have any kind of preliminary big picture expense thoughts going forward? And I have one follow-up.
Hi, Corey, it's Cristiana. Thank you for your question. First of all, big picture in terms of R&D and SG and A cost we continue to invest aggressively invest in our clinical development portfolio as well as on our commercial operations. What you are seeing with R&D this year and the expenses coming on the lower side is that we were able to reallocate expenses that were previously, for epocatastat and, baricitinib to our other late stage development programs. So that allowed us to be able to push forward the other development programs without seeing an increase in R&D.
Going forward, however, as we have discussed in the past, we are looking to invest in R&D based on the quality and the progress of the program. So, based on data and merits of the programs, if those programs progress, through later stage of development, you would expect you would expect that to drive R and D expenses. In terms of Q4, we reiterated the guidance that we provided on both R and D and SG and A because there is timing factor for some of the expenses on both lines that we expect to be more back end loaded into Q4 of 2019. And therefore, we continue to be comfortable with the initial guidance that we have provided.
Okay. That's helpful. And then my follow-up is a quick one for Steven. How much, how much patient follow-up will you wait for in that fight 201 PEMI bladder study before potentially top lining that data?
Hi, Corey, Steven. So typically, across the board ballpark follow-up in these sort of studies required by regulatory agencies is around 12 months, but that's for your last responder. So you what I'm saying is you complete if that last very last patients responder, you typically require about 12 months. So if you think we've just recently in completed recruitment on the study, we're looking at data sometime mid-twenty 20 or beyond to get a complete view of that picture. Across the board on our bladder data.
Okay, perfect. Thanks for taking the questions.
The next question is from Evan Sigerman of Credit Suisse. Please go ahead.
Hi all. Thanks for taking my question and congrats on the progress. So, Christian, one for you. How would you characterize your capacity to transact? I know Herve mentioned some high level thoughts on BD.
And then I have a follow-up on that. Just basically what are some characteristics of assets that you would consider bringing in house? So one for you, Cristiano and one for you, Herve.
So in terms of the capacity, as we have discussed in the past, we have a strong balance sheet. We currently have 2 on our balance sheet. So that gives us the opportunity to consider bringing in external assets to add to our internal portfolio. In terms of the nature of the assets, we are looking at programs that could contribute to revenue diversification and growth in the midterm timeframe. So continuing to add to growth as we're getting closer to the Jakafi potential patent expiry period.
So bringing additional growth driver then obviously makes a lot of sense for us. So do you want to Yes,
I mean, the type of assets are fairly it's very clear. I mean, the first is obviously a methodology oncology. Anything that would be good science that would be novelis that would provide a benefit That is unique in the field of cancer treatment could fit with our portfolio where we have a very strong hematology franchise, both in Europe and the U. S. And where we have emerging solid tumor franchise, also in the U.
S. And a little bit later in Europe. So that makes sense in terms of timing we are looking at the window between 25:30. And it's fairly obvious why, because that's where we would need more diversification. The second aspect is to complement our IMF and PV franchisees where there are new mechanisms that can be complementary to what we have in our portfolio and where obviously our leadership in MF and PD could be reinforced by external assets if any benefit could be shown from this.
And then we have a little bit of a longer view on the non oncology aspect. As we said, we will be commercializing our rock screen in the U. S. We may have partnership if needed, but we will be leading the commercialization in the U. S.
We will be partnering our dermatology assets outside of Europe and U. S. And we are still looking at what's the best strategy for Europe. So there, there could be also potential BD aspect to the dermatology franchise. We are very confident in the benefits.
We are showing both in atopic dermatitis and as you saw in Vitiligo, it's a fairly striking data with the long term follow-up. And we believe there is a true value in this franchise and complementing it with, external assets could be an option. It's not, it's not absolutely mandatory because we believe in the U. S, we can build the team to successfully commercialize there could be some complement to it. So it's fairly clear.
It's a metallurgy oncology for 25 to 30 where that's where the contribution to the top line will be the most valuable. It's lifecycle management of MF and TV and potentially if we find the right assets in dermatology or somewhere in a non cancer immunology, it could be also another dimension.
Okay. And then I just follow-up there. I mean, are we talking $1,000,000,000 to $1,000,000,000 or really haven't you give color on that on terms of what you'd pay?
So the main focus is on what I would characterize as packing type of assets that we can bring in either through licensing or M and A. So we are agnostic in terms of the structure, whatever makes sense.
Okay. Thank you.
The next question is from Jay Olson of Oppenheimer And Co. Please go ahead.
Hey guys, congrats on the quarter and all the progress. I had a couple of questions. Could you comment on, what were the best available therapies that Jakafi be in Reach 2? And is there overlap between those best available therapies in Reach 2 and Reach 3? And then, just to follow-up on pemigatinib.
Could you provide some additional color on how the enrollment is going in fight 205 and FIGHT207 and also the bladder cancer continuous dosing cohort?
Yes. Hi, Jade, it's Steven. Thank you for your questions. So both reach to and reach 3 are randomized studies against, best available therapies. Just to mention, reach 2 that we've just said reported out as positive and will be presented at an upcoming medical meeting to our knowledge is the 1st randomized study in graft versus host disease that is reported out as positive.
So that's really good news obviously for patients and for us. The therapies themselves are listed on clinicaltrials dot gov, but just to give you a sense, there are slight differences because there are different disease entities for Reach 2 that include things like anti thymocyte globulin, extracorporeal photopheresis. There's mesocchymal cells, low dose methotrexate, microphenylate and even M2 inhibitors. Like everolimus can be used. For Reach 3, there's some overlap, but they also in addition because chronic graft versus host disease include therapies like rituximab, and imatinib as well as ibrutinib, which is approved in chronic graft versus host disease.
The complete list is available on, on clinicaltrials dotgov. Enrollment to the second part of your question on the studies you mentioned for the entirety of the Pemigatinib program, obviously, includes our completed part in cholangiocarcinoma and then the ongoing first line study there, then the large bladder cancer program and then the tumor agnostic as well as a smaller entity that we don't speak about much, but very important to patients is an AP11 milder proliferative neoplasm. We don't guide to exact, dates in terms of enrollment other than when we start and sometimes when we end in the studies. But just to give you a sense that, the agnostic study, 2 or 7, which you mentioned, has started enrollment, and we'll be looking at different driving mutations, there. And then we expect to complete, as I just alluded the second line bladder study before the end of this year and have data latter part of next year.
And then we're about to start the first line bladder study. So that gives you a sense of the the cadence of enrollment and the entirety of the program.
The next question is from Ren Benjamin of JMP Securities. Please go ahead.
Congratulations on a great quarter. I guess just as a follow-up regarding the Reach 2 data, Stephen, is there anything there that kind of increases your confidence, in regards to Reach 3, or are the 2 diseases really, you know, separate and distinct acute versus chronic?
Ren, thank you. It was great to see a randomized study against best available therapy being positive and again, as I just said, we look forward to sharing those results to you. So it further does increase our confidence in what we already know per se that ruxolitinib is a really good drug. For steroid refractory acute graft versus host disease. Chronic does have a slightly different pathophysiology as it's more a disease of fibrosis with more skin manifestations as opposed to a more apoptotic disease in acute where there's more sort of cell death in the liver NGR tract, but there's enough overlap and our proof of concept data was strong enough that we remain confident in chronic graft versus host disease We do think although the pathophysiology, there's a little bit of a difference, there's a good read through and we're confident in getting that data next year.
Got it.
And then just as a follow-up, the Vitiligo studies have started. Can you give us any sort of a sense if it's enrollment is on track for an epic schedule and kind of all the sites open?
Yes. So you're correct. The Vitiligo studies have started. As you saw in my formal presentation, we just presented the 52 week data at EADV with continuing improvement, quite dramatic in patients through 1 year. The studies have just recently started, but I will tell you it's a pleasant surprise to us working in dermatology these studies accrue really, really well.
So that we start to open quickly. We have dedicated dermatology centers across the globe. We're good at doing clinical research to put patients on quickly, and we up and go in with Guster and very positive about it.
Great. Thanks for taking the questions.
Our next question is from Alethia Young of Cantor Fitzgerald. Please go ahead.
Hey guys, thanks for taking my question. Congrats on the quarter. 2. 1, maybe Steve, can you talk a little bit about, best supportive care for re stream and how it varies across the world? Do you think there's any kind of variability that you should consider in the trial.
That's ongoing. And the second question probably is more for maybe Herve. I guess, I'm just curious how you think about kind of term margins for the business and where we are exactly in kind of the peak cycle for Jakafi seems like there's still a lot of room to move you're building in PV kind of an awareness and there's penetration that could be had. But maybe if you can frame that from a high level perspective, that'd be helpful. Thanks.
Hi, Alethia. It's Steven. So you do allude to something we see in graft versus host disease, not only across the world, but even within the United states and even within cities themselves, there are treatment differences in patterns at bone marrow transplant centers in how and how people have treated this condition to date and continue to both in terms of preoperative regimens and actual regimens. Which is exactly why for best available therapy, we have to account for a number of therapies. So there's no dramatic differences across the world compared to just as I said, even within the U.
S. Itself. We always, as a matter of course, do analyses that look at differences if there are any between different parts of the world explain response rates, etcetera. So those analyses will be done. Typically, you do the U.
S, Western Europe And Rest of World Analysis we'll look at those, but nothing that we're concerned about.
Regarding the cycle, I mean, the sort of medium to long term cycle of the business, obviously, the growth of Jakafi in the U. S. Is very key to the entire P and L of insight. As you can see, I mean, this quarter, in fact, is growing even faster than the previous one versus last year. Now Q3 last year was a little a little bit lower maybe than should have been, so the ratio of the 25 percent growth for Jakafi U.
S, maybe slightly higher than the true trend over the year, I think we are more into 20%, but which is still very, very strong for a sort of a 7th or 8th year of of commercialization. And we see a lot of potential for continued growth of Jakafi in the U. S. In MF. It is still volume growth, patients' volume is increasing in MF.
And in TV, as we said, there is larger potential for 2 reasons. It's because the treatment rate is still on the low end below 50% and duration of treatment for every patient studied on Jakafi is very much longer than what we have in MF. So what we see is a sort of chronicization of the disease in MF that is leading to this growth potential is obviously higher. We are not changing the long term guidance very frequently, but we have made a lot of progress towards the numbers that we we gave a few years ago of 2.5 to 3, and that's something we are very confident in. Regarding the P and L itself and the margin as Kristian has said, I mean, we are investing in R&D based on the quality and the required work for the assets.
That we have. And so it may be fluctuating, as you have seen, when a pachytherstad did not work as planned to say the least, you could see that it has a positive impact on the R and D budget, which is, obviously, the paradox of our industry is that if you stop a project. It will improve margins. But obviously, our goal is not to manage the margin short term proactively. But to maximize the value to the company and the shareholders by doing the right clinical development for each of the assets that we have in our hands.
At the same time, you may have seen from 2014 to today is that we are in the trend of improving ratios in the P and L where the growth of the top line has been not every single quarter, but on if you look at it on a cumulative 4th quarter in a row, that margin has been improving over time. And that's where, why we are, where we are today, you know, where the the P and L has the shape that it has today. So that's something we will continue to look for but it may include quarters where investment will increase because some of the assets that we have are requiring and increase investment at some point. So overall, the way we have been sort of looking at this is certainly growth of the top line is driving our ability to invest in R&D and they are the 2 components to create value that will be sustainable for the long term for insights.
Our next question is from Vikram Purohead of Morgan Stanley. Please go ahead.
Hi, good morning. Thanks for taking the question. So I wanted to go back to long term Jakafi and the tail on that franchise. And I had two questions on Jakafi Lifecycle Extension Program. So, I believe earlier, you'd alluded to possibly getting some extended release data in 2020.
So I just wanted to see what the status of that program was if it's in the clinic yet or not. And then secondly, I believe the last time we saw some Jakafi combination data was at ASH last year in combination with the PI3K molecules. I just wanted to see when further data from that combination could be available as well as from other combinations like PIM and itacitinib, in the MF setting?
Vikram, hi, it's Steven. So thank you for your question related to Ruxolitinib Lifeside management, which we do as something for ruxolitinib itself as well as for myeloproliferative neoplasms in general. There are 3 pillars to the program, and you mentioned all of them. So firstly, in terms of formulation work, which you brought up, That's been ongoing this year. It involves, an extended release approach in terms of formulations and bio availability and bioequivalence work.
That is underway. It's been going. And we'll, as you just said, complete in 2020 at some point, and then we'll use it to have regulatory discussions probably through the middle of 'twenty one. We'll find an appropriate meeting to present it at, but I'll remind you that we actually presented some rux little XR data in 2011 with the 25 milligram XR tablet. So we have already, and that work is ongoing and progressing well.
In terms of the 2nd pillar combinations, we are running, as you said, a PR3 kinase delta combination. That's the most mature of them. We also have a rux plus perm combination and a rux plus itacitinib combination ongoing. We'll have our sales data in house to look at ourselves, with RUX Plus Delta approximately end of this year. And we'll find in appropriate meeting to present it at, in 2020 and make decisions go forward decisions or not in either 1st or second line fibrosis when we look at the completeness of the data.
We'll also should have enough data with PIM and Edacitinib also to present in 2020 at an appropriate meeting. And then the 3rd pillar and very important is new targets to look at in MF and PV in collaborations with academia and different vendors, including epigenetic screens to look if there are any new targets there. And we haven't announced anything publicly yet, but that's a very, very active endeavor as well.
Okay, appreciate it. Thank you.
The next question is from George Farmer of BMO Capital Markets. Please go ahead.
Hi, good morning. Thanks for taking my questions. I was wondering if you could comment a bit on Pemigatinib and how you, you believe this molecule differentiates from other FGFR inhibitors?
So it's Steven. I'll go first, Ashmi, want to add something to it. We're an extra for 1, 2, 3 specific inhibitor. We know that the PK and PD effects of this compound really well. We've done both intermittent dosing as well as continuous dosing.
And we've got a very good PD marker pharmacodynamic marker in hyperphosphatemia. So we can dose to that. And as I said earlier, manage appropriately, all compounds obviously chemically are different Obviously, the only approved FGFR inhibitor currently is erdafitinib, the Janssen compound, and that does hit FGFR4 as well and may explain some of the difference in safety profile that we seen, but we'll wait for the full datasets to bear that out. As regards to the other compounds, I just I don't know enough to comment on any cash wants to add anything.
Yes, I mean, I think you covered the major points there, Steven. We feel that pemigatinib is probably the most selective FGFR inhibitor out there. We're focused on SGFR1, 23. We don't really touch the other isozymes, you know, if we're just in biochemical assays or cellular assays, etcetera. We have a what we think is a great PK profile clinically.
So overall, we feel it's a balance of, optimal selectivity for our target protein as well as the clinical profile to sort of leverage that selectivity in an optimal way.
Okay, great. That's helpful. And then I know it's early days, but do you have any sense for, duration of therapy in the steroid refractory acute setting with Jakafi?
Well, we can only go on, again, the REACH1 trial and we believe, in fact, in the duration of response of 173 days that's in our label, where therapy isn't changed or, and the patients don't come off for whatever reason. So, that's what we're going by by we don't really have from a commercial standpoint a follow-up yet on what the true nature is, but we do know that it's successful that patients seem to be staying on it for a long time. As you know, in, graft versus host disease in general, but it's particularly in acute graft versus host disease, physicians of bone marrow transplant docs want to taper off drugs, like steroids. And then even like Jakafi over a period of time, but just so they can do it safely and make sure they fully managed the effects of DVH DB where they do so.
Okay, great. Thanks very much.
The next question is from Mara Goldstein of Mizuho. Please go ahead.
Great. Thank you very much for taking the question. Just a couple of questions. And one is on the promotional sensitivity, on Jakafi in the PV indication. You mentioned that you thought that that category could get 50% penetrated.
So I'm wondering where the resistance is among the prescribing community? And is that something that is subject to, also greater promotion. And then just secondarily, if you could update us on the status of the commercial organization for pemigatinib as you have an NDA filed for cholangiosarcoma?
Sure. So, we, Jack Fi is actually promotionally there across all indications. You know, it's both MF and PV can sometimes most of our treating physicians and healthcare professionals don't see these patients that often, sometimes they're often worried about some of their other patients that might have lung cancer or pancreatic cancer. So they don't pay enough attention to the symptoms in fact that these patients are experiencing and other indicators that their disease may be getting worse So we have oncology clinical nurse educators. We have obviously our MSLs and we have our sales representatives continuing to try to educate health care professionals that they need to look more closely at these patients, particularly as PV patients who are suffering, and that's one of the reasons we do our educational campaign, obviously, to encourage patients themselves to go out and infect advocate for themselves if they don't feel like they're getting the appropriate treatment.
And your second question was, oh, the commercial footprint for Pemagetinib, so we do plan in fact to add a few more people, in 20 to get ready for the Pemegatinib launch. So, we do, we're going to keep the full amount of current FTEs against Jackify for MF and PV, we're going to increase slightly the number of FTEs that we have that are targeting graft versus host disease in bone marrow transplant centers and then a few FTEs that will be concentrated on pemigatinib. We also have a couple of oncology clinical nurse educators and obviously our market access people that are in fact fully ready for and fully trained on pemigatinib and cholangiocarcinoma for the launch in 2020.
Our final question is from Christopher Mariah of Nomura Instinet. Please go ahead.
Just maybe touching upon some of the Ruxo lifecycle management plans I recall previously if I had a BH inhibitor in the pipeline, I've been looking at that target. And at EHA, there was some great data for the 1 CPI0610 in myelofibrosis and has the potential to potentially work on the second line, but also maybe augment CroXO in first line. That's myelofibrosis. And I was wondering if perhaps you could comment on your progress there with 18 editors and how you might be looking at that as a particular target? Thank you.
Yes. Christopher, hi, it's Steven. So just to remind, we ourselves had a BRD program. So obviously, we had preclinical data that showed that RUX plus that target, had enhanced potentially enhance the efficacy in myelofibrosis. And we ran into toxicity in terms of an on target toxicity in terms of thrombocytopenia and currently put ourselves the program on clinical hold with the regulators.
The comp you allude to a competitor that PRD program which showed you write some interesting data and have an abstract in for future medical meeting that they may show more and we'll follow that closely. We are interested in anything that enhances RUX activity and we'll keep looking across that. Our own programs are are there for us to use should we need to resurrect them.
The the toxicities, I think it sounds like, the competitor had, but as you noted, that was something you're still investigating. Any improvement on the therapeutic index there. Maybe any mechanism reason why you think yours might be different from from the competitors? Thank you.
Yes. So I won't address this directly, but it's known that BOD inhibitors have on target thrombocytopenia that can be profound. So you have to weave the therapeutic ratio carefully in terms of potentially dosing to get there, I can't speak to the competitor compound there.
There are no additional questions at this time. I'd like to turn the call back over to Urvi Oppenaut for closing remarks.
Okay. Thank you. Thank you all for your time today and for your question. And we look forward to seeing you at upcoming investor and medical conferences. For now, we thank you again for your participation in the call today.
Thank you, and goodbye.
This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.