Executives
Maria Cantor - Senior Vice President of Corporate Affairs
Harvey Berger - CEO
Edward Fitzgerald - CFO
Timothy Clackson - Chief Scientific Officer
Martin Duvall - Chief Commercial Officer
Analysts
Jason Kantor - Credit Suisse
Cory Kasimov - JPMorgan
Joel Sendek - Stifel Nicolaus
Michael Yee - RBC Capital Markets
Rachel McMinn - Bank of America Merrill Lynch
Nicholas Bishop - Cowen & Company
Mike King - JMP Securities
Ying Huang - Barclays Capital
Katherine Xu - William Blair
Jonathan Eckard - Citi
Gena Wang - Leerink Partners
Echo He - Maxim Group
Ariad Pharmaceuticals (ARIA) Q4 2013 Results Earnings Conference Call February 25, 2014 8:30 AM ET
Operator
Thank you for holding for Ariad Pharmaceuticals’ fourth quarter and full year 2013 financial results conference call. [Operator Instructions] At this time, I would like to introduce Ms. Maria Cantor, Ariad’s Senior Vice President, Corporate Affairs. Please go ahead.
Maria Cantor
Good morning, and thank you for joining us. This morning, we report on financial results for the fourth quarter and full year of 2013 and provide financial guidance for 2014. With me on this call are Dr. Harvey Berger, our Chairman and Chief Executive Officer; Ed Fitzgerald, Chief Financial Officer; Dr. Tim Clackson, President of R&D and Chief Scientific Officer; and Marty Duvall, Chief Commercial Officer.
Please note that during this call, we'll be making forward-looking statements. These statements are subject to factors, risks, and uncertainties, including those that are detailed in our Form 10-K for the year ended December 31, 2012 and other SEC filings that may cause actual results to differ materially from the results expressed or implied by such statements. Now, here's Dr. Berger with our opening remarks.
Harvey Berger
Thank you very much, and good morning everyone. Our focus for 2014 is clearly building shareholder value. This will be accomplished in part through a successful relaunch of Iclusig in the U.S., continued strong commercialization of Iclusig in Europe, further advancement of 113, and definitive progress in our lead discovery program.
We are off to a solid start in each of these fronts as we execute against the strategic operating plan we put in place late last year. This plan was built around specific investments that will help us to restore confidence in Iclusig while continuing to develop our product pipeline. I will review this in more detail, but first, Ed Fitzgerald will cover our financials.
Ed Fitzgerald
Good morning, everyone. I refer you to our press release, issued this morning, for a summary of our financial results for the three-month and 12-month periods ended December 31, 2013. I will focus my comments this morning on an overview of our financial guidance for 2014.
We anticipate cash used in operations in 2014 will be in the range of $155 million to $175 million. This is an approximate 25% reduction compared to our 2013 cash use in operations. We anticipate R&D expenses in 2014 will be in the range of $140 million to $150 million, encompassing development activities for Iclusig, AP26113, and ongoing discovery research efforts. Approximately 75% of our R&D expense is planned for Iclusig development activities.
We anticipate SG&A expenses in 2014 will be in the range of $135 million to $145 million. Approximately 50% of the SG&A expenses relates to U.S. and Europe commercial activities for Iclusig.
Our R&D and SG&A operating expense guidance for 2014 includes estimated noncash expenses of $35 million to $45 million, consisting primarily of stock based compensation and depreciation and amortization expenses. We expect that our cash, cash equivalents, and marketable securities at December 31, 2014 will be in the range of $60 million to $70 million, sufficient to advance our programs to mid-2015.
Let me now turn the call back to Harvey.
Harvey Berger
Thanks very much, Ed. Our focus in 2014 is on patients with resistant and intolerant Philadelphia-positive leukemias, and on ensuring that we have optimized the benefit-risk of Iclusig in these patients. This begins with a strong relaunch of Iclusig in the U.S. followed by continued pricing and reimbursement approvals, demonstrating the value of Iclusig and commercial launch on a country by country basis in all of the major markets of Europe.
We will begin a new clinical trial for Iclusig in the second half of this year as part of our FDA post-marketing requirements. This will be a randomized, multi-arm trial to characterize a range of Iclusig doses and to inform its safe use in patients with refractory forms of chronic phase CML.
Importantly, data from this trial will allow us to better understand the efficacy and safety profile of Iclusig when treatment is started at doses less than 45 mg per day, the currently approved dose.
Long term follow up with patients in the pace and phase I trials of Iclusig continues. The dose of Iclusig in these patients has been reduced to 15 mg or 30 mg per day, which should provide further insights into the maintenance of response and the incidence of vascular Iclusig events at Iclusig doses. We expect to present updated data from these trials at this year’s ASCO meeting.
The phase I-II clinical trial of Iclusig in resistant or intolerant CML in Philadelphia-positive patients in Japan is ongoing, and we expect that the data from this trial, combined with the other completed and ongoing trials of Iclusig outside of Japan, will allow us to file for regulatory approval of Iclusig in Japan next year.
In addition to actively pursuing distribution agreements for Iclusig in central and eastern Europe, as well as in the Middle East, just as we have done in Australia, we plan to partner Iclusig in Japan and perhaps in other countries in Asia. We have no timeframe now on when we might announce a partnership, but we consider this decision as an important step in building shareholder value.
Beyond CML, we continue to explore the use of Iclusig in patients with a refractory GIST and have observed promising early results in patients who have failed multiple treatments. The trial is almost fully enrolled. We anticipate this phase II trial will reopen and complete enrollment upon lifting of the partial clinical hold, expected in the second quarter. We expect to present initial data from the GIST trial at this year’s ASCO meeting.
In addition to the Iclusig trial in GIST, we have many investigator-sponsored trials exploring the potential benefit of Iclusig in various hematologic malignancies and solid tumors, all characterized by specific genetic markers. Some of these trials have been on clinical hold, but not all, and we expect them to come off hold on a case by case basis throughout this year. ISTs in medullary thyroid cancer and in FLT3 positive AML are off hold, and now open for enrollment.
Beyond Iclusig, we are focused on the advancement of 113, a potent ALK inhibitor with a particularly favorable clinical profile. We’ve evaluated 113 extensively in the ongoing phase I/II trial and now have experience in over 120 patients at doses up to 300 mg per day. This patient experience has provided clear insights into the behavior of the drug at different dose levels, its efficacy, and particularly its safety profile.
Early in the trial, we observed a pulmonary syndrome in some patients after receiving their first dose of 180 mg per day. We subsequently learned that these findings were transient and that patients could tolerate sustained dosing at this dose level very well.
We have now dosed 20 patients with 113 at the regimen of 90 mg per day for one week prior to increasing the dose to 180 mg per day. We have not seen any cases of the early onset transient pulmonary syndrome using this dosing regimen. This gives us great confidence that this dosing regimen of 113 is well tolerated and safe, facilitating sustained dosing at 180 mg per day.
To obtain the most information about the safety and efficacy profile of 113 from this important pivotal trial, we’ve decided to test two dosing regimens in a randomized but noncomparative clinical setting. We expect to have sufficient data to support approval of both of these dose levels.
This pivotal trial of 113 in ALK positive non-small cell lung cancer patients resistant to crizotinib will begin shortly, by the end of the first quarter. The trial will be global and include approximately 220 ALK positive patients, including those with brain metastases, all of whom have failed crizotinib. We have previously reported very encouraging data on 113 in patients with brain metastases.
In the second half of this year, we expect to nominate a potential best-in-class development candidate. This molecule will be another product of our internal discovery program, driven by computational methods and structure-based drug design. The candidates will be an orally active small molecule drug targeted against an oncogenic kinase in a class that is well understood and clinically validated, but with a unique target product profile.
We’ve submitted data from various Iclusig and 113 clinical trials to the ASCO meeting, as I mentioned earlier, and expect to be in a position to present data from 1) the ongoing Iclusig phase I and pace trials, 2) the EPIC trial in patients with newly diagnosed CML, 3) the phase II trial of Iclusig in refractory GIST patients, and 4) the ongoing phase I/II trial of 113.
Let me turn the presentation over to Marty Duvall, who will review the Iclusig commercialization progress.
Martin Duvall
Thanks, Harvey, and good morning everyone. I am pleased to provide an early update on the progress of our Iclusig relaunch in the U.S. and our ongoing commercial advancement in Europe. Specific to the U.S., we are encouraged by the early launch dynamics through the first five weeks, which includes the following.
We have made significant progress on converting the patients receiving Iclusig through the single patient IND mechanism. Remember that 305 patients received a supply of Iclusig through the single patient IND program. To date, with five weeks of product availability, approximately 180 U.S. patients have already transitioned from the IND to commercial supply of Iclusig.
This number will continue to grow over the next several weeks as patients use up their Iclusig obtained through the IND mechanism. In total, we expect up to 230 patients of the 305 IND patients who received an Iclusig supply to transition to commercial drug by the end of the quarter.
Additionally, we expect that approximately 7% to 10% of patients will remain on Iclusig therapy from the IND program but will qualify for free drug through our patient assistance program. We have a plan in place to transition as many of these additional patients as possible to commercial supply.
As expected, the remaining 18% to 20% of patients, predominantly those with advanced phase disease, will discontinue Iclusig treatment from the IND program. Above and beyond the SIND patient conversions, we are gaining new commercial patients. Over 100 new prescriptions have been written for Iclusig since the resumption of marketing and distribution in mid-January.
It is important to note that many of these patients have not yet received a commercial shipment and may be on a Quick Start supply as they move through the managed care approval process. We are also pleased to note that over 250 unique physicians have written a prescription for Iclusig, both in the academic and community settings. This includes more than 80 physicians not associated with the IND program last year.
In summary, for the U.S., the rapid return of Iclusig to the market last year has been helpful as we work to rebuild confidence in Iclusig. Feedback from the field suggests that as physicians gain comfort with the benefit-risk profile of Iclusig, confidence will continue to grow in the months ahead. This growing comfort level will be associated with the continued expansion of the prescriber base and increase utilization of Iclusig in the months ahead.
Turning now to Europe, our E.U. commercialization continues in the early launch countries, and we’re very pleased with our progress to date. In the fourth quarter, commercial revenue recognition was limited to Germany, the U.K., Austria, Italy, and the Netherlands. In 2014, we will expand commercialization of Iclusig to 15 E.U. countries and Switzerland, based on achievement of pricing and reimbursement approvals.
We have phased our commercial operations resource deployment to match the local market dynamics to be sure on a country by country basis we have the properly sized organization for the market. Based on this plan, we will have a modest commercial footprint in select countries in Europe. Iclusig is now approved in Switzerland and indicated for adult patients with all phases of CML or Philly-positive ALL, for whom treatment with no other TKIs is appropriate, or for patients with the [unintelligible] mutation.
In the first half of this year, our sales opportunity expands to Switzerland and Ireland. In the second half of 2014, we expect to begin promotional activities in Italy, France, Sweden, Denmark, Norway, Finland, Belgium, Portugal, and Spain.
In Europe, the Pharmacovigilance Risk Assessment Committee, or the PRAC, of the EMA, is conducting a complete analysis of the safety data on Iclusig as continuation of a process that began last year. We expect the conclusion of this Article 20 procedure in May, when the CHMP issues its opinion.
The Article 20 procedure is a standard assessment aimed at a better understanding of the adverse events that have been observed with Iclusig and potential ways to further improve the benefit-risk. We do not anticipate any major changes to the indication statement.
I look forward to sharing additional updates with you throughout this year on our continued commercial progress. Now, let me turn the call back to Harvey.
Harvey Berger
Thanks very much, Marty. With that, operator, please open the lines to analysts’ questions.
Question-and-Answer Session
Operator
[Operator instructions.] Our first question is from Jason Kantor with Credit Suisse.
Jason Kantor - Credit Suisse
In terms of the commercial relaunch of Iclusig in the U.S., and you mentioned that you have over 100 new patients on the drug, can you speak to the demographics of those patients relative to what you saw in the IND program?
Martin Duvall
At this point in time, with it being early days since the relaunch, we’re not going to fully characterize the patient population, but please look forward, at our Q1 call, or the results from Q1, for us to provide the details similar to those that we’ve been providing in the past. You may recall, from the single patient IND program, we saw a mix of patients across all lines of therapy, and 60% of those patients were chronic phase patients.
Jason Kantor - Credit Suisse
In terms of the pricing and reimbursement negotiations in the E.U., can you speak to how those are going in the other countries that you have not launched? And also, in terms of the revenue recognition for France, how will that occur over the second half of the year? Will it be lumpy, or will it be spread out evenly?
Harvey Berger
I’ll let Ed address the revenue recognition question. I’ll handle the pricing and reimbursement negotiations. Those continue. Some countries have timed the pricing and reimbursement review to the complete PRAC assessment, so we think that this is good news for us, as it will provide full visibility to the label and the outcome of that procedure, which we think will be differentiating and positive for Iclusig.
So those negotiations continue. You may have read information recently from Germany regarding early assessments, and we have pricing discussions that are occurring with German authorities beginning this week. We’ve made good advancements with IFA in Italy.
So things are proceeding relatively according to plan, although some countries have moved out a little bit toward that PRAC assessment. And this is fully consistent with what we shared at the JPMorgan conference.
Ed Fitzgerald
In regard to the recognition of the French revenue, which at this point in time, as we’ve disclosed, has not been recognized, the timing of that will be triggered when we have final pricing determination based on our negotiations with the authorities in France. So we would expect, when that final price is determined, you’ll see that revenue triggered.
Harvey Berger
That means it will be triggered in one shot, at one point in time.
Operator
The next question is from Cory Kasimov of JPMorgan.
Cory Kasimov - JPMorgan
My first question is regarding your Iclusig dose ranging study, to begin in the second half, is that also going to be exploring a range of doses from 15 mg to 45 mg? And will it allow for titration up or down? And then a follow up on the GIST program. Can you remind us what the anticipated follow up time is there before collecting data?
Tim Clackson
Regarding the dose exploration study, our final design of that is something that we’re still refining, and clearly it would also then be subject to discussions with the regulatory agency. But in general, the points you mentioned are things that we’re considering, evaluating at multiple doses. And one of the questions is whether there would be a mandatory or an optional dose reduction at some of those levels. But it’s very likely that we’ll be looking at those levels, that include the 30 mg and the 15 mg levels.
Regarding GIST, the primary endpoint is clinical benefit response at eight weeks, which includes an objective response, a complete or partial response, or confirmed stable disease. And so we’ll be reporting the data in that context, but there’s also a series of other follow ups, including PET scans for some patients. So it will be a pretty comprehensive analysis.
At the time of hold on the trial, we had, as Harvey mentioned, largely enrolled the trial, with only seven slots remaining, and so the [unintelligible] that we submitted to ASCO and the data that we would update will be a pretty substantial package.
Operator
The next question is from Joel Sendek with Stifel.
Joel Sendek - Stifel Nicolaus
I really appreciate all the detail on all the patients. One thing I’m confused about from the fourth quarter, though, is how much of the $8.3 million in sales were from the U.S. sales from back in October? Can you help us with that?
Edward Fitzgerald
In the fourth quarter, of the $8.3 million, $5.4 million was from the U.S. in October.
Joel Sendek - Stifel Nicolaus
And the 100 new prescriptions, just to be clear, that’s over and above any patient that’s transitioned? But I get the sense that you’re kind of suggesting that we’re not going to see any of the revenue associated with that in the first quarter, because of the Quick Start program? Is that a correct interpretation?
Martin Duvall
Sorry for that miscommunication. I’m just suggesting that through the first five weeks, there were 100 patients in the queue above and beyond the single patient IND. Some of those patients have already received a commercial shipment. Others have received the Quick Start. Others are going through the managed care process. So they all could indeed, given that there’s still five weeks left in the quarter, receive at least one commercial shipment during the quarter.
Operator
The next question is from Michael Yee with RBC Capital Markets.
Michael Yee - RBC Capital Markets
First, I think in early January you mentioned that there were 370 on the IND, but today you only mentioned 305. So could you just comment on what happened to the other 65 patients? Also, regarding the specifics on [unintelligible] free drug, and 18-20 that have discontinued, do you expect the specific dynamics to be similar in the [unintelligible] setting for this year?
Martin Duvall
First of all, regarding the 370 and the 305, the difference in those two numbers, the 65, there were 370 physicians who requested Iclusig through the single IND mechanism in the fourth quarter of last year during the suspension. Of that, 305 of those patients were actually shipped drug.
So one might speculate that those 65 patients, perhaps they were toward the latter part of the program, and physicians decided to wait for recommercialization, perhaps those patients moved on to different therapies. As we’ve pointed out in the past, the program is a pretty onerous one on the part of the physician and their participation. So submitting for the single patient IND request is just the first step in the process.
One might speculate that a portion of those 65 patients are translating into some of those new patients that I mentioned, but I haven’t done that complete analytics. Certainly, as we move through the first quarter and report on the first quarter, I’ll provide greater detail.
As for the forecasting of the 305 and kind of how we arrive at those numbers, first of all, it’s based on where those patients fit today, five weeks into the launch, and what we know. It’s also based on the historical experience of commercialization last year.
In terms of the number of patients that move on to free drug through a patient assistance program, typically in the U.S. we refer to that as an indigent patient program, on average, that represents somewhere in the 7% to 10% of the U.S. population that seek healthcare do so through that type of a mechanism. So it’s based on historical experience. So I hope that helps.
Operator
The next question is from Rachel McMinn with Bank of America.
Rachel McMinn - Bank of America Merrill Lynch
I have a study question, and then also a commercial question. For the dose ranging study that you talked about, it seems like that’s really the most important fundamental study that you’re going to be running, that’s really going to address whether or not this [unintelligible] dosing can achieve a better balance of efficacy and safety. Are you going to be providing [unintelligible] data, so we get visibility on a regular basis, or is it really like after a prolonged period of time, and you have [unintelligible] follow up, that you’ll be releasing data?
And then on the financial question, you talked about $60 million to $70 million ending the year. Is that sufficient working capital to really kind of go into 2015, or should we think about you needing to raise money before year-end?
Tim Clackson
As I mentioned, we haven’t finalized and fully agreed to the design of the dose ranging study. When we do, and when we kick it off, we’ll discuss whether we will have a formal interim analysis.
But in principle, you can think of the trial as asking at least two questions. One was are lower doses sufficiently efficacious, and do they give the kind of efficacy profile that we’ve already seen at the 45 [unintelligible] dose? And secondly, what is the adverse event profile of those doses?
We would expect to have the answers to the efficacy questions relatively early in the trial, given that we’ve seen the majority of our responses to Iclusig in the three-month timeframe in previous trials.
With safety, I think we would expect to see an ongoing delivery of data. We would certainly get early readouts, but clearly one can’t get definitive one year follow up data until you’ve had one year of follow up. So whether we would capture those pieces of information in formal interim analyses, or whether we would just be following the trial on an ongoing basis, as we did for example with the PACE trial, remains to be decided. But we’ll provide clarity at the time of trial launch.
And to your introductory comment, we are certainly very motivated to have this trial up and running as soon as possible.
Edward Fitzgerald
On your second question, the numbers we’ve provided, I think, are there to define the runway that we have, and they are based upon no assumptions whatsoever in terms of partnering, distributorships, any other sources of capital. It is the base working plan, on top of which we add any partnerships, potentially the Japan partnership, potentially raising capital in the public markets, or any other sources of capital that we access.
Obviously, we’re not going to wait until second quarter next year to address this, and as I mentioned in the introductory remarks, we’re working very diligently on all of those options, and we’ll, of course, this year, pursue one or more of those options.
And we’ll know more as we work our way through this year as to what steps we’re going to take in terms of having access to more capital. But there are many ways in which we can achieve that, and we’re very focused on doing it in the best way possible.
Operator
The next question is from Nicholas Bishop of Cowen & Company.
Nicholas Bishop - Cowen & Company
I have a couple of quick ones on Europe. The first is in the French deferred revenue, there was a pretty big jump in the fourth quarter from kind of a steady $2 million or so, up to $4 million. Just curious if you can comment on what happened in France this quarter. And also, kind of as we think about how the launch is likely to proceed in other countries, like Germany and the U.K., what sort of ramp relative to France is reasonable to expect?
And then the second one on Europe, I think you’ve said in the past that there were 2,300 or so potential new patients per year in Europe. Are all those in the 15 countries you’re going to enter? Or are they distributed across a large number of countries?
Martin Duvall
In terms of the French deferred revenue or the big jump, we’re just seeing an increase in patients treated in France at that point in time. So I think from a French KOL perspective and the work done, partnership in the PACE trial and EPIC trial, we have some very strong advocates in that country for our drug. And I think what we’re seeing in terms of utilization across the patient base in France is an excellent example of a successful precommercialization process.
In terms of other countries, and how we would expect the ramp to proceed, it’s very different on a country by country basis, the way care is delivered. And the first country you mentioned is Germany, and it provides an excellent contrast to the French situation. In France, we see centralization of care from a CML perspective, and a country that’s very concentrated in several regions with major centers of care, where patients in France seek therapy to treatment their CML and Philly-positive AML.
So the uptake there, where one has good relationships, buy-in, participation to the development program, belief in the drug, it’s going to be very strong. By contrast, a country like Germany is more similar to the United States, where care is shifted across academic centers as well as community centers. So a patient in Germany may go to the local oncologist, or may go to an academic center. So this really brings the point made earlier, regarding the footprint, and the footprint is much different.
So each country on an individual basis is different. It’s based on participation, background, belief, advocacy in the drug, but also the way in which care is delivered. So I look forward to, as we move through the pricing reimbursement for each, to further characterize and assess the uptake relative to our expectations in each of those countries.
And on the overall patient numbers, I believe the number that we shared is 2,500 resistant intolerant patients in Europe, switching therapy in 2014, who would be potentially eligible for Iclusig.
Harvey Berger
And those are mainly in the major markets. We’ve always focused on the 15, 16 major markets in Europe.
Martin Duvall
About 80% of those would be in the big five alone. So I hope that helps.
Operator
The next question is from Mike King with JMP Securities.
Mike King - JMP Securities
I have a couple related to the relaunch. Marty, you had said that 18% to 20% of the patients discontinued, I guess this is just another way of asking a question that was asked earlier, about the characteristics of the patient population that was on the IND program. Is that a discontinuation rate that we ought to think about? Because that seems relatively high for such a relatively short period of time that they were on the program.
Martin Duvall
I’ll make some comments, and maybe if Harvey has anything to add. First of all, let’s reset on what that patient population looked like. 60% of them were chronic phase, and 40% were advanced phase patients, so we have a good portion that are 40%. Also, keep in mind that on November 1, it wasn’t the first day that these patients were on Iclusig therapy. Essentially, most of these patients, if not all, but a handful, were continuing on Iclusig therapy. So what we don’t have is a lens to how long they might have been taking the drug.
So if you think about the first four weeks of the program, let’s say, when we were shipping three months’ worth of Iclusig supply, it’s likely, if we consider that the majority of patients had been on the drug for a few months, were kind of in that six-month median range of Iclusig therapy for advanced phase patients, if we equate back to the PACE trial. So I would caution you against looking at it in terms of a November 1 start and patients discontinuing so quickly, because those patients had been on drug previously.
Mike King - JMP Securities
So that’s kind of a moving average, you’re saying?
Martin Duvall
I don’t know if it’s a moving average, but I think you’ve got patients who are not newly starting on Iclusig with advanced phase disease. They’re patients who almost certainly have been on Iclusig largely with advanced phase disease who have been treated for quite some time, obviously then got moved over, emergently, onto the single patient or emergency IND. And so you’re going to have a higher discontinuation rate in that snapshot of the Philadelphia-positive leukemia population than what you’d see in routine clinical practice.
Mike King - JMP Securities
And remind me, I forget exactly what the number was, of patients on drug at the time of the market withdrawal. It was 600 and some odd?
Martin Duvall
640.
Mike King - JMP Securities
So of the difference between the 375 and the 640, do we have any idea what happened to the remaining patients and what they went on, and whether that population that maybe now coming back onto Iclusig?
Martin Duvall
We haven’t really characterized that yet, and I would suspect that some moved on to different therapies, some will come back to Iclusig. We do hear anecdotal reports. As we get through the entire quarter and get better visibility on all the analytics, I’ll consider that as part of an update on the next call.
Operator
The next question is from Ying Huang of Barclays.
Ying Huang - Barclays Capital
First of all, I guess you anticipate the lifting of the project hold in the second quarter. Can you remind us exactly what is required by the agency to lift that partial hold? And then in terms of the around 80 patients who came out of the single patient IND [are all] commercial drug today, the other 100, I guess, NRx we saw since January, can you give us a breakdown exactly how many of those patients are second line, third line, versus even the later lines?
Tim Clackson
For the GIST trials, which I think is what you’re asking specifically about, we have to respond to the formal hold letter from the FDA with a protocol amendment, which they will then approve. That is, among other things, designed to address whether there will be any dosing changes or dose reduction recommendations for patients, and the amendment and [unintelligible] update the safety information that’s in the protocol. Patients need to be reconsented, we need to update the investigator brochure, and there are a few other more minor pieces of documentation.
But the most important one is to gain agreement with proposed protocol changes that could include recommendations for [unintelligible] medications and dose reduction. So working through that, and bearing in mind that we’re looking for a unified solution to those issues with many trials, is what we’re working through right now.
Each trial is different. The risk benefit considerations are different for each patient population, and in some cases we’re also working with different divisions within the FDA. For example, GIST is not obviously the [unintelligible]. So that’s what we’re working through. We have partial control over the timing. Obviously, on our side we can work very diligently, but then the FDA also has flexibility in the timing they take. And that’s why we’re being conservative in the timelines we’re communicating.
Harvey Berger
I think I would also add that we made a conscious decision in the fourth quarter of last year not to push through the changes in the protocols to bring trials off clinical hold until we had agreement with the FDA on the way in which they wanted to handle Iclusig for the marketplace, for the commercialization in Philadelphia-positive leukemias.
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Because we thought it would be very important to have consistency, as Tim mentioned, not only among the clinical trials that were on hold, but between trials that were on hold, trials that we put on delay because we wanted to align all the different trials with one set of answers. We wanted that to be aligned with the commercial utilization plans, both in Europe and the U.S., so that we had sort of a global solution or a global answer to the outstanding questions.
So we probably could have made it happen faster, but we think at the end, the best outcome, as Tim pointed out, is a unified approach across hematologic malignancy, solid tumors, trials that are covered by IND, those that are not covered by IND, trials in the U.S. and Europe, with one unified approach. That’s now what we’re doing, so that I think we’re now on a very straightforward track to put all those trials behind us.
Martin Duvall
And as for the question on the patient mix, I just remind everyone the single patient IND pool - and this characterizes 370 applications that were received - were distributed approximately 20% were second line, 40% were third line, and 40% later.
In terms of characterizing patients we’ve seen in the first five weeks, I think we’re going to hold off until we have a full view of the quarter and certainly look forward to providing that information on our next call.
Ying Huang - Barclays Capital
If I may just have a follow up, you [unintelligible] on the definition of cardiovascular treatment emergent adverse events with the FDA before. Have you guys resolved that with the agency?
Harvey Berger
We’re not trying to resolve that difference. I think the label, which you’ve seen, with Iclusig, that is the basis for the relaunch of Iclusig in the U.S., includes the large number of events that the FDA identified. We felt that that issue would be better addressed over the long term in the academic setting, in the academic community, to try to standardize definitions and interpretation of safety data, in TKIs in general, and certainly in this class of TKIs.
So it’s not a matter of reconciling the differences. There are differences. EMA has looked at the data one way, more akin to what we have said and believe. The FDA has looked at it somewhat differently. We don’t need reconciliation of those differences in order to provide good advice to physicians on how to optimize the benefit-risk and ensure that the right patients are receiving Iclusig around the world.
So I think that’s really how we now look at that issue. It will obviously come back as we have presentations at academic meetings, subsequent follow up of the PACE trial and of the phase I trial. All will be important academic questions that quite honestly right now is not the focus, either of commercialization or the clinical questions that are being posed. The best way to ultimately get at the issue is to prospectively study it in our dose evaluation trial, with prospective definition of events and the significance of the vascular occlusive events.
Operator
The next question is from Katherine Xu with William Blair.
Katherine Xu - William Blair
Just real quick, can you just remind us regarding the U.S. commercial team, the size now and the players in place?
Martin Duvall
Quick reminder, in 2013 we had approximately 65 in the field, and what we’ve disclosed at this point is that we’ve reduced that by a little bit more than 50%. So we’re in the 30 range from a U.S. perspective. They are all in place, and were in place January 13.
Katherine Xu - William Blair
And then in terms of the launch as well, we’ve been watching some of the prescription data, and it seems like it hasn’t really come back since the relaunch. I was just wondering, would that be something we should be looking forward to? Or do you think the company will kind of just maintain silence on that for now?
Martin Duvall
The [IMF] data, we made a strategic decision, I’m sure that’s what you’re referring to, so you’re not going to see that until an internal decision is reversed. So we are currently blocking that data. And it’s for competitive strategic reasons. Based on our experiences last year and our knowledge of prescriber base distribution, physician preference, by TKI, utilization, we felt we were in a pretty good place to blind our competitors to our uptake in 2014. So we believe that not sharing that data with our competitors is providing us a unique competitive advantage here at the outset in 2014. We’re going to continue to revisit that decision as the year progresses, and as our potential interest in understanding dynamics on a physician by physician basis changes.
Katherine Xu - William Blair
And then one quick question, on the GIST, if we get some interesting data and the hold comes off, when could we see potentially a pivotal study for the indication to begin?
Tim Clackson
I think that’s something that we would probably discuss in the future once we’ve looked at the data and really had the chance to come to the proper conclusions and discuss with investigators. So ASCO will be the next time point where we would, presuming acceptance, be able to talk about the data in a bigger context.
Katherine Xu - William Blair
And the next oncology drug candidate, are we looking at more from a heme perspective, or a solid tumor type of potential molecule?
Tim Clackson
We’re not giving more details beyond what we provided in the press release today.
Operator
The next question is from Jonathan Eckard with Citi.
Jonathan Eckard - Citi
I was wondering if you could remind us what the number of patients was on commercial drug before you stopped commercializing it back in October. And then looking at the financial guidance, if you kind of back into what you assume for revenues in 2014, and I’m just trying to understand what are going to be the key drivers of reaching those revenues given the new start point, where we are in the new label indication. Is it primarily U.S.? Is it primarily the French reimbursement lump payment? And then I have a question around the E.U. process.
Martin Duvall
What we’ve talked about in terms of our U.S. commercialization in 2013, in total, we believe that based on our data, about 1,000 patients were treated in the U.S. on Iclusig from a commercial perspective in 2013. And in October, at the time of the marketing suspension, we believe approximately 640 patients were on the drug at that point in time.
In terms of the math you’re doing on the back of the envelope, I can’t read into that too well. I’ll just make a general comment that we’re expecting pretty equal contribution from the U.S. and Europe as it relates to our 2014 performance. So certainly we expect meaningful revenues from both geographies this year.
Jonathan Eckard - Citi
And then on the E.U. Article 20 process, based on the web, it seems like the next step is - maybe you’ve already done it - is submitting the responses to the questions by March 5. Is there any other step between now and the May step, where you’ll get formal feedback from them? Or is it the next step that you’ll hear from the EMA or [Proacta], the May update?
Tim Clackson
You’re correct with the deadlines. We’re dotting I’s and crossing T’s at the moment on the response. The procedure is very tightly choreographed in time in Europe, and so the timing that is publicly available is exactly what will happen. The document will be reviewed by the rapporteur and co-rapporteur, the [unintelligible] will meet, and the feedback will be provided along the timetable that has been publicly disclosed in May.
Jonathan Eckard - Citi
Okay, because I could see the timeline, but it’s not clear if there’s any official dialog with the sponsor during each of those steps.
Tim Clackson
In general, no.
Operator
The next question comes from Gena Wang with Leerink Partners.
Gena Wang - Leerink Partners
First, I wonder, will you include the dose ranging trial with the Japan filing? And also, I wonder what are your plans for the EPIC trial?
Tim Clackson
Let me answer the Japan question first. At the time that we file in Japan, if there are any meaningful data or patient exposure data that would be relevant to the filing, I’m sure we would discuss with the PMDA whether they would like to see those data. But at this time, what we’re considering for the bulk of the filing is what we described earlier, which is the global trials, the ex-Japan trials, phase I and phase II, coupled with the specific Japan phase I/II trial. That should form the bulk of the data. Other experience for the drug will also be included as context. For example, the EPIC data.
And then to move on to EPIC, you asked what the plans were. I’m not sure what you mean, but the next events there are that we are preparing the clinical summary document that will be filed with regulatory authorities along the timelines that we’ve committed to within the next couple of months. And as you know, we submitted the data to ASCO, and we hope that that abstract is accepted, and that would be the first public disclosure of the data from the trial.
Operator
The next question comes from Echo He with Maxim Group.
Echo He - Maxim Group
I just want to clarify, when you answered one of the previous questions, you said $5.4 million is from the U.S. Did you mean that $5.4 million from the U.S., the rest from Europe? I actually just want to know the revenue split between the U.S. and Europe during the quarter.
Edward Fitzgerald
Yes, we indicated that $5.4 million of the $8.3 million was from the U.S.
Echo He - Maxim Group
So considering you have $4.1 million deferred revenue in France, at least right now I should consider in Europe that technically, it should be somewhere around $7 million in sales?
Edward Fitzgerald
Yes, that’s correct.
Echo He - Maxim Group
And also, when you have this deferred revenue, it’s a pretty significant amount, in France. In the second half of this year, if the price is settled as you expect, and then should you record it into that quarter, you fix the price as one-time?
Edward Fitzgerald
Yes, the results of the pricing and reimbursement negotiation with the French authorities will be to establish the pricing for France. And that will then allow us to properly trigger the revenue that has not yet been reported.
Echo He - Maxim Group
I’m just asking, you probably will record all the deferred revenue into one quarter?
Edward Fitzgerald
Yes, that is our expectation.
Operator
The next question is a follow up from Rachel McMinn with Bank of America.
Rachel McMinn - Bank of America Merrill Lynch
I just wanted to follow up on two things. One, can you just comment on, the demand that you’re seeing of the 100 patients that are outside of the transitioning IND program, do you think that that’s really reflective of a bolus of patients? Do you have any sense of how we should be thinking about it? And then I wasn’t sure if the person who asked this question on backing into sales actually specified, but implying $70 million to $75 million in revenues, is that the right number to think about for this year?
Martin Duvall
I’ll come in on the bolus, and I’ll defer the second part of the question. I’ll further characterize that those 100 patients, as we move through the quarter, I don’t know that I would necessarily consider them a bolus. I think if we find that a good portion of them - if half of those patients were from the single patient IND mechanism that were never shipped drug, I guess we could characterize that as some type of slight bolus. So I’ll do some more analytics on that and certainly report back on the next call. But it’s certainly my hope that we are able to take the pace of new patient adds and continue to grow that throughout the year.
Edward Fitzgerald
Your second question, I think, was akin to is $75 million ballpark anticipated revenues for this year? Is that what you’re asking?
Rachel McMinn - Bank of America Merrill Lynch
Yeah, that’s basically what you get when you take your numbers and do some subtractions. I just wanted to check in with you to make sure that’s the message you want us to take away.
Edward Fitzgerald
I think you’re doing the arithmetic correctly. That, I think, is roughly the right number, based on what we’ve disclosed to date.
Operator
We have no further questions at this time. I would like to turn the call back over to Dr. Berger for closing remarks.
Harvey Berger
I’d like to thank everybody for joining us this morning on the call, and I look forward to seeing many of you at our upcoming investor events. Thank you very much, and again, I appreciate all the good questions.
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