Jazz Pharmaceuticals plc (JAZZ) Q3 2014 Earnings Report, Transcript and Summary

Katherine A. Littrell - Vice President of Investor Relations Bruce C. Cozadd - Co-Founder, Executive Chairman and Chief Executive Officer Matthew Young - Chief Financial Officer and Senior Vice President Russell J. Cox - Chief Operating Officer and Executive Vice President Michael P. Miller - Senior Vice President of U.S. Commercial Jeffrey K. Tobias - Chief Medical Officer and Executive Vice President of Research & Development

Annabel Samimy - Stifel, Nicolaus & Company, Incorporated, Research Division Michael Eric Faerm - Wells Fargo Securities, LLC, Research Division Ken Cacciatore - Cowen and Company, LLC, Research Division David A. Amsellem - Piper Jaffray Companies, Research Division Louise Alesandra Chen - Guggenheim Securities, LLC, Research Division William Tanner - FBR Capital Markets & Co., Research Division Jason M. Gerberry - Leerink Swann LLC, Research Division Gregory B. Gilbert - Deutsche Bank AG, Research Division Jessica M. Fye - JP Morgan Chase & Co, Research Division Irina Rivkind - Cantor Fitzgerald & Co., Research Division Gary Jay Nachman - Goldman Sachs Group Inc., Research Division John L. Newman - Canaccord Genuity, Research Division Jonathan Eckard - Citigroup Inc, Research Division Marc Harold Goodman - UBS Investment Bank, Research Division Douglas D. Tsao - Barclays Capital, Research Division John T. Boris - SunTrust Robinson Humphrey, Inc., Research Division David W. Maris - BMO Capital Markets U.S. Oren G. Livnat - JMP Securities LLC, Research Division

Welcome to the Jazz Pharmaceuticals plc Third Quarter 2014 Earnings Conference Call. Following an introduction from the company, we will open the call to questions. I will now turn the call over to Kathy Littrell, Head of Investor Relations at Jazz Pharmaceuticals. Please proceed.

Thanks, Crystal, and thanks to each of you for joining our Investor Call. Today, we reported our third quarter financial results and updated 2014 financial guidance in the press release. The release and the slide presentation accompanying this call are available on the News and Events section of our website. With me for today's call are Bruce Cozadd, CEO; Matt Young, CFO; Russ Cox, our COO; Jeff Tobias, our CMO; and Mike Miller, our Head of U.S. Commercial. Following some remarks, we'll open the call for your questions. I'd like to remind you that some of the statements we will make on this call relate to future events and our future performance, rather than historical facts, and are forward-looking statements. These statements include future financial results and commercial development and regulatory plans, expectations and projections, and the potential timing of future events. Examples of forward-looking statements include: Our 2014 financial guidance; anticipated growth prospects for our products; planned commercial efforts, including product supply efforts and future events related to the rolling launch of Defitelio in Europe; expected and potential submissions and our interactions with our regulatory agencies, corporate development initiatives; anticipated litigation-related events; and the expected future events related to planned and ongoing clinical trials. These forward-looking statements involve numerous risks and uncertainties that could cause the actual events, performance and results to differ materially. These risks and uncertainties are identified and described in today's press release, the slide presentation accompanying this call and under Risk Factors in our Form 10-Q for the quarter ended June 30, 2014, and our Form 10-Q for the quarter ended September 30, 2014, that we expect to file shortly. We undertake no duty or obligation to update any forward-looking statements we make today. On this call, we will discuss several non-GAAP financial measures, including historical and expected 2014 adjusted net income attributable to Jazz, and the related per-share measures and historical and expected 2014 adjusted SG&A and R&D expenses. We believe that these non-GAAP financial measures are helpful in understanding our past financial performance and our potential future results. They are not meant to be considered in isolation or as a substitute for comparable reported GAAP measures. Reconciliations of GAAP to non-GAAP financial measures discussed in this call are included in today's press release and the slide presentation accompanying this call. Both are posted in the News and Events section of our website. I'll now turn the call over to Bruce.

Good afternoon, everyone, and thank you for joining us. During the third quarter, we achieved revenues of $307 million, an increase of 32% compared to the third quarter of 2013, driven by strong sales of our key products, Xyrem, Erwinaze and Defitelio. We realized adjusted net income of $146 million in the third quarter, reflecting the attractive margins in our business. GAAP net income for the quarter was $26 million. During the third quarter, we made significant progress toward our 2014 goals. We had 2 positive pre-NDA meetings with FDA focused on our planned NDA submission for defibrotide in the U.S., and we advanced our clinical development pipeline by opening 2 new clinical trials for enrollment, one in pediatric narcolepsy and the other in children with acute lymphoblastic leukemia. Also, enrollment in the Phase I JZP-386 study was completed. We have made significant progress on maximizing value from the 3 transactions we completed earlier this year, launching Defitelio in 4 additional European countries in the third quarter and advancing JZP-110 toward the clinic, in addition to advancing our U.S. regulatory efforts with defibrotide. We remain focused on our corporate development efforts, as we look to add differentiated products that are meaningful in size to Jazz and will create additional shareholder value. We continue to prioritize corporate development activities aimed at products on the market or close to market while also continuing to assess development candidates that are complementary to current franchises. I'll now update you on our sleep and hematology/oncology franchises, including information on key commercial, legal, regulatory and clinical development activity during the quarter. Finally, Matt will review our financial results for the quarter and provide comments on our guidance. I'll start my comments with our sleep franchise and our lead product, Xyrem. In the third quarter, demand remained strong, and the average number of active Xyrem patients grew to approximately 12,050, from 11,000 in the same period of 2013. During the third quarter, we had bottle volume growth of 9% year-over-year. Even in this increasingly restrictive reimbursement environment, where payers and managed care organizations are implementing more processes such as prior authorizations, to verify that appropriate patients receive therapy, we are pleased that we have not seen meaningful changes in our overall reimbursement coverage. We are committed to providing patients and health care providers with the appropriate level of support services to enable them to successfully navigate the complex payer environment. In particular, we continue to work closely with SDS to improve the timeliness and effectiveness of the processes for filling and refilling Xyrem prescriptions while preparing to handle increases in reimbursement-related activities, including typical first quarter pressures. Efforts to increase Xyrem prescriptions written by our low- to mid-decile physicians continue to contribute to our sales growth year-over-year. We are expanding the Xyrem call universe through the identification of new opportunities for our sales representatives to educate additional physicians on treatment with Xyrem. Another important initiative has been to grow the diagnosed population of narcolepsy patients who may be candidates for Xyrem therapy, through education efforts with health care providers, as well as an unbranded disease awareness program. During our narcolepsy disease awareness campaign in 8 U.S. cities, which concluded in August, there were approximately 300,000 unique visits to the morethantired.com website, over 7,500 physician finder tool hits and approximately 6,600 completions of the Epworth Sleepiness Scale with a total score greater than 10. Over 70% of the hits in each of these categories were attributed to the 8 target cities. We believe that the disease awareness initiative, over time, will increase the number of patients diagnosed with narcolepsy and may help reduce the time from disease onset to diagnosis. Our review of insurance claim databases to identify lagging indicators such as increased use of diagnostic tests, for example, the multiple sleep latency test, is encouraging. We will continue to monitor these data over time to identify whether there is an increase in the diagnosis of narcolepsy. In October, we enrolled the first patient in our Phase III study of Xyrem in pediatric narcolepsy patients with cataplexy. We expect the study to enroll 100 patients. Turning to a brief intellectual property and legal update on Xyrem. Patent litigation continues in the District Court in New Jersey. No trial dates have been set in any of the cases, although we anticipate the trial of a portion of the case against the first filer, Roxane, could occur as early as the second quarter of 2015. We have also submitted preliminary responses to covered business method, or CBM, petitions that certain of the ANDA filers filed in the second quarter. The CBM petitions asked the Patent Trial and Appeal Board of the U.S. PTO to review and cancel certain patents covering our restricted distribution system for Xyrem. Our preliminary responses assert, among other things, that the challenged patent should not be subject to CBM review. We expect the board to rule on whether review will be instituted for any of the patents subject to the CBM petitions during the first quarter of 2015. If the patent office decides to institute the CBM reviews, we expect that the board would issue its decision after review, as early as the first quarter of 2016. And we recently received a Paragraph IV notification from another ANDA filer, Watson Pharmaceuticals. Turning to a brief regulatory update on the Xyrem REMS. As discussed in prior calls, we initiated dispute resolution with FDA earlier this year related to the Xyrem REMS. We met with FDA regarding our request for supervisory review during the third quarter, and we are currently addressing FDA's interim request for additional data before it issues a response, which we expect to receive before year-end. Turning to JZP-110. We are currently working on final study designs for the Phase III studies and are preparing to manufacture clinical trial material for those studies. We anticipate initiating one Phase III study in excessive daytime sleepiness and narcolepsy and 2 Phase III studies in excessive daytime sleepiness and obstructive sleep apnea in the first half of next year. We are also planning an extension site to evaluate long-term safety data. Finally, as to JZP-386, our deuterium-modified sodium oxybate compound license from Concert. Enrollment in a first-in-human trial evaluating the safety, pharmacokinetics and pharmacodynamics of JZP-386 is complete. We anticipate receiving initial data before year-end and expect to provide an update on the outcome of the study after we and our partner, Concert, have evaluated the data and determine next steps. Now on to the hematology/oncology franchise. We are pleased with the strong growth of Erwinaze this quarter. Our efforts continue to be focused on educating health care providers and cancer centers on identifying hypersensitivity reactions to asparaginase in the treatment of acute lymphoblastic leukemia. We continue taking steps to expand production capacity and to improve the Erwinaze manufacturing process as we seek to build a higher level of inventory and increase Erwinaze supply over the longer term. Our clinical study of Erwinaze in young adults is open for enrollment. We are continuing to add study sites in both the U.S. and E.U. As to JZP-416, the first patient was recently enrolled in the pivotal Phase II clinical study we are running in collaboration with the Children's Oncology Group in children who've experienced a hypersensitivity reaction to treatment with pegaspargase therapy for their acute lymphoblastic leukemia. The Defitelio launch in the European Union continues to progress well. Since March, Defitelio has been launched in Germany, Austria, the U.K., Denmark, Finland, Norway and Sweden, as well as in Italy under a special reimbursement law. During the rest of 2014, we anticipate launches in Ireland, the Netherlands, and in Italy under final pricing and reimbursement approval. Our key focus in Europe remains establishing solid pricing and reimbursement in order to maximize access for patients in need, and we continue to engage in pricing and reimbursement submissions and discussions throughout the E.U. Now a brief U.S. regulatory update on defibrotide. We had 2 productive pre-NDA meetings with FDA in August, a CMC and a clinical, nonclinical meeting. During these meetings, FDA provided feedback with respect to our planed NDA submission. And as a result of these discussions, we do not anticipate needing to complete any additional clinical trials prior to NDA submission. We are pleased with the progress that we have made today in collecting and remediating existing defibrotide clinical data. We are planning to initiate a rolling NDA submission by the end of the year and anticipate completing the submission in the first half of next year. Defibrotide has Fast Track Designation in the U.S., and we plan to work with FDA to gain regulatory approval for defibrotide for the treatment of severe VOD as quickly as possible. Our defibrotide development team is assessing potential clinical strategies to evaluate defibrotide in the treatment of earlier VOD, that is VOD before it has progressed to multi-organ failure, and in prevention of VOD in high-risk patients. We plan to provide an update on our development plans during the first half of 2015. Also, in light of previously published data, we continue to assess the best approach to understanding defibrotide's potential role in prevention of VOD and acute graft versus host disease. Finally, for a more general regulatory update. As previously disclosed, we received a Form 483 in April at the conclusion of a pharmacovigilance inspection conducted by FDA and responded to FDA to address those observations. In August, FDA issued its establishment inspection report to us, which indicates the inspection is now closed. Matt, let me now turn the call over to you.

Thanks, Bruce, and good afternoon, everyone. We are pleased with our strong performance in the third quarter as we saw adjusted EPS attributable to Jazz increase by 31% year-over-year. We expect continued strong top line growth for 2014, driven by growth in sales of Xyrem, Erwinaze and Defitelio. We are increasing our total revenue guidance to a range of $1.15 billion to $1.17 billion and increasing our adjusted EPS guidance to a range of $8.20 to $8.35 per share. Net sales of Xyrem for the quarter were $204 million, up from $154 million in the third quarter of last year. We are maintaining our guidance for Xyrem net product sales in a range of $765 million to $780 million for 2014. We expect high-single to low-double digit bottom line growth in 2014. Turning to Erwinaze. Third quarter worldwide net sales were $52 million, up 18% from the same period in 2013. We are increasing the lower end of our guidance for Erwinaze net product sales to a range of $190 million to $200 million for 2014. For Defitelio/defibrotide. Third quarter worldwide net sales were $19 million compared to pro forma net product sales of $13 million in the third quarter of 2013. We are increasing our previous defibrotide net sales guidance to a range of $65 million to $70 million. In the third quarter, Prialt net sales were $6 million compared to $11 million for the same period in 2013. As a reminder, sales in the third quarter of 2013 included $5.7 million sales to Eisai Co. for distribution in Europe. We anticipate sales to Eisai during the fourth quarter of 2014. Turning to operating expenses. Adjusted SG&A expenses for the third quarter were $77 million or 25% of total revenues compared to $60 million or 26% of total revenues for the third quarter of 2013. The increase in adjusted SG&A expense was primarily due to higher headcount and expenses resulting from the expansion of our business. Adjusted R&D expenses for the third quarter were $18 million or 6% of total revenues compared to $10 million or 4% of total revenues for the third quarter of 2013. The increase was primarily related to increased costs associated with the advancement of our sleep and hematology/oncology product candidates, as well as life cycle management activities for our existing products. We anticipate higher R&D expenses as we advance our clinical development programs and continue our regulatory efforts. While the expenses in SG&A and R&D can vary quarter-to-quarter, we expect to be within our guidance range for the full year. We are maintaining our 2014 guidance on adjusted SG&A in the range of $315 million to $325 million and maintaining our guidance on adjusted R&D in the range of $65 million to $75 million. As of September 30, 2014, cash and cash equivalents were $575 million, and we have available capacity under our existing revolving credit facility of $425 million. During the third quarter, the main uses of cash were: The repayment of $300 million under the revolving credit facility; the upfront payment of $75 million to Sigma-Tau for the acquisition of rights to defibrotide in the Americas; tax payments; capital expenditures; and the repurchase of our ordinary shares. During the third quarter, we repurchased approximately 44,000 shares at an average cost of $148.38 per share, leaving us with $33.6 million remaining in our previously announced $200 million share repurchase program. In August 2014, we completed the placement of $575 million principal amount of 1.875% exchangeable senior notes due 2021, resulting in net proceeds to us after debt issuance cost of $559 million. As of September 30, 2014, the principal balance of the company's total debt was $1.5 billion. Foreign currency gain during the third quarter of 2014 was $6.5 million or $0.08 per diluted share, primarily due to the strengthening of the U.S. dollar against the euro. In closing, we continue to pursue attractive opportunities to expand our business through our corporate development initiatives. We are pleased with our progress year-to-date, including our completion of multiple transactions and execution on commercial, development and regulatory objectives, all of which we believe continue to support our focus on acquiring or developing important, differentiated medicines for patients while generating value for our shareholders. Thank you for joining us on the call today, and I'll now ask Kathy to make a brief comment about our Q&A session.

Thanks, Matt. [Operator Instructions] With that said, I'll turn the call back to the operator to open the line for your questions.

[Operator Instructions] Our first question will come from the line of Annabel Samimy from Stifel. Annabel Samimy - Stifel, Nicolaus & Company, Incorporated, Research Division: Had a few questions on just volume versus pricing on Xyrem, specifically. It looks like you only added about 300 patients, which was a slight slowdown from the uptick that you saw last quarter. So I would have expected a little bit more support from the volume growth. Can you just give us a little bit of characterization of what's going on there given that you had been targeting the lower-decile physicians and also increase the educational efforts now? On defibrotide, can you help us understand whether there's any volume -- big volume orders to distributors over there? Or is that pure demand?

Okay. Let's start with your Xyrem question. Of course, we typically provide our growth numbers year-over-prior year. And you saw, we reported the 9% volume growth. I think the number of patients -- average patients during the period grew approximately the same amount. And I'll also say we're maintaining our Xyrem guidance. So I wouldn't say anything about the quarter surprised us from a volume perspective. We continue to see good growth from our low- to mid-decile prescribers. And as we've said, the non-branded disease awareness program we just completed in August is really expected to have an impact over time, not so much in the current period. So I would say right on track with Xyrem. And with respect to defibrotide, maybe I'll let Russ make a comment on that.

Yes. So we had commented that in the second quarter, we did see some stocking into different countries, and we are not seeing the same level of stocking taking place in the third quarter. Annabel Samimy - Stifel, Nicolaus & Company, Incorporated, Research Division: So it's more demand rather than stocking?

That is correct.

Our next question will come from the line of Michael Faerm with Wells Fargo.

My question is regarding M&A. If you could please give us kind of your latest thinking in terms of priorities, what types of size transactions you'd consider? What sort of timing we might expect with respect to future transactions? And with regard to size, maybe some color on how high you'd be willing to push your leverage and whether you'd use stock for the right transaction?

Mike, let me ask Matt to take this one.

Sure. Hey, Mike, thanks for the question. So as we've said previously, we continue to be very focused on corporate development, and our priority remains on near or close-to-market or on-market opportunities. While principally, in our current franchises, we would look beyond that, we also are looking at development-stage opportunities within those franchises. So the priority really hasn't changed. All of that continues to be driven by a focus on medicines that do something substantial for patients that have the opportunity to generate strong margins to offer us long-term growth and good exclusivity and, again, continue to be a focus with our business overall. We continue to see the breadth of those opportunities given our size and geographic footprint today as having increased. So the number of situations we're willing to look at and can look at has increased, and we continue to see an attractive set of opportunities out there. As we've said before, it's difficult to comment specifically on timing because in any one transaction, it's not -- they don't follow a perfectly linear path. And as it relates to leverage and the currency we may use, I think, as we've said before, we would be willing to push our leverage higher up to levels that you see elsewhere across our industry in the 5x or north of 5x leverage range if we believed we were buying an asset that changed the overall portfolio of our business in a way where we felt we would easily be able to reduce that leverage quickly over time and that our risk was diversified. And we would be willing to consider large transactions that would contemplate that. We have also said that we would be willing to use our equity in the right situation where we feel the opportunity from a value and risk perspective was something that we believe would be attractive to our shareholders as we think about relative value of currencies and absolute value of what we're looking to accomplish.

Our next question will come from the line of Ken Cacciatore from Cowen and Company.

I was just wondering in terms of defibrotide, if you could give us the initial indication in the U.S. kind of patient size of those patients that traditionally progress to VOD with stem cell transplant versus if you were able to actually get it used in what you term prevention or earlier treatment. Could you give us the magnitude difference of both? And then, also, just wondering, on your valproate coadministration patent, it appears that Amneal, Ranbaxy and Par have each certified Paragraph IV to that patent, but the lead litigant, Roxane, has not yet certified. So I was wondering if there's anything we conclude from them not filing yet on that patent. Could you discuss that?

Okay, Ken. On the first part of your question sort of defibrotide market size depending on indication, let me have Russ walk through some of those numbers.

Sure. I'll just give you a flavor for some of the differences between the E.U. and the U.S. and then specifically in the U.S. So in the E.U., we see in terms of number of hematopoietic stem cell transplantations about 35,200 in the E.U., and there's about 6,300 then in terms of patients that are high risk for VOD, and then the reported incidents of VOD is the 3,600 range. So that's sort of the high range of the numbers that we've seen in the E.U. As it relates to the U.S., it's less but still substantial, where you see about 19,500 HSCTs. You see about 3,000 patients at high risk for VOD and somewhere between 1,000 and 2,000 with the reported incidents of VOD. So that's -- those are your high-end numbers. Our goal, obviously, was to look at a label that's consistent with what we've seen in Europe. But clearly, our goal would be to work towards early treatment where we think that we'll see better outcomes over time.

And, Ken, on the second part of your question, I think I'm going to disappoint you a little bit by declining to comment on what ANDA filers may be doing in terms of their strategy. I can tell you, obviously, we continue to feel we've got a robust intellectual property portfolio around Xyrem, including, but not limited to, the specific patent you referenced that expires in 2033. But not going to get into ANDA filer by ANDA filer discussion of that.

Our next question will come from the line of David Amsellem from Piper Jaffray.

So just on Xyrem. Can you give us some more color on the reimbursement headwinds that you're seeing; I guess the extent to which you're seeing outright denials? And to what extent are the headwinds limiting volume growth? And then, secondly, on 386, if safety checks out fine and you potentially have a differentiated PK profile, would it be reasonable to conclude that you can move directly into Phase III?

So on the first one, maybe I'll let Mike Miller address the Xyrem reimbursement environment.

Yes. Thanks, Bruce. So the environment is becoming increasingly restrictive, and it really has been focused on specialty pharma and the orphan drug category or space. And the PAs have increased environmentally, I would say that. And the purpose of those PAs is to really make sure that the drugs are used appropriately and diagnosis is well documented. But I will say that our coverage is quite good. Our approval rate is in the almost 80% range, so our denial issue is not a large one. We continue to provide the services that we think enable timely refills and filling of first scripts at the pharmacy for both providers and patients. So we feel quite good about it.

Okay. Maybe I'll have Jeff talk about 386 and the potential paths forward with that.

Right. So in anticipating the results from the study, you can imagine, there could be any number of different findings that come out of that trial. But assuming the scenario that you set out, that everything looked really interesting, there's still a number of questions, I think, that remain for any product that is changing the delivery pattern of Xyrem to patients. And certainly, it's not well-established as to what that might do as regard to impact on efficacy and other parameters. So there may need to be a little bit of additional work before that and going right into pivotal trials. Again, depending on the results, you might want to think about other type of approaches, but there is additional work that would need to be done.

Our next question will come from the line of Louise Chen from Guggenheim.

So my first question is with respect to potential pool of patients for Xyrem. I know you've had some initiative to increase that from 50,000 to 55,000 up to 75,000 to 100,000 over time; just curious how that initiative is playing out. And then, secondly, with respect to o U.S. business, curious how large it is today and where do you want to grow that to over the next several years.

Yes. Maybe I'll take the second half of your question first and then have Russ take the first part of your question. With regard to x U.S., I would say this is a partnered product for us outside the U.S. with UCB and Valiant, our 2 partners. And so we don't really comment too much on exactly what's going on there. It's not a major driver of our revenue growth for the product. Russ, you want to take the first half of the question?

Yes, sure. So you heard us comment that we're looking at penetration levels of about 12,000 patients currently in the U.S. We've seen claims data that gets us anywhere from 50,000 to 65,000 in terms of current patients that are diagnosed in the U.S. And there are databases that show you anywhere from about 155,000 to 200,000 patients who actually have narcolepsy. We've seen some claims data to get us in the $175,000 -- or 175,000-patient range. So there are a series of different numbers that we've seen, but I think that it's pretty clear that you've got over 50,000 patients there in the U.S. that are diagnosed today.

Our next question will come from the line of Bill Tanner from FBR Capital Markets. William Tanner - FBR Capital Markets & Co., Research Division: I had one follow-up maybe, Jeff, for you, just on 386. I mean, I know the trial was intended to measure the PK profile and safety. So let's say, it's safe. Is there a bogey as it relates to the half-life, I guess, that one would need to see to take it forward? Is there any analogue, any observation from Concert as it relates to other compounds, what they see with extended half-life? And then, I guess, the second question, Bruce, you mentioned something about, on the Xyrem REMS dispute resolution that the FDA has requested additional information. I guess, I hadn't heard that before, and I'm wondering is that a departure from what the process has been like in the past? And I guess wouldn't ask you to hit your cap whether or not that's a good sign or not, but just help us understand if this is a little bit different as you go higher within the agency.

So, yes, the bogey for 386 is any number of them, if possible, but the one that first comes to mind would be if, indeed, the half-life is too long. So you end up with a product that has effect going into the warning, and that could be problematic with the product. William Tanner - FBR Capital Markets & Co., Research Division: So there's kind of a window --

[indiscernible] William Tanner - FBR Capital Markets & Co., Research Division: Sorry.

Pardon?

So I was going to say maybe there's kind of a window then, not so much a hurdle, because you could go -- it could be too short and too long, so somewhere in the middle kind of...

Yes, right [indiscernible]

I think that's the right way to think about it and what the shape is in between and what that's doing to the patients. On your second question, Bill, you are right. This is new information since our last update a quarter ago. We had previously said we expected a response back in the third quarter. In fact, what happened is FDA did ask us for some supplemental information, which they then will react to. And we expect now that, that response, which we had targeted for the third quarter is of this quarter, meaning a fourth quarter event. What you read into that? I wouldn't read anything into that other than FDA is actively engaged in this process, and we're working with them to make sure they have the information they want to have. William Tanner - FBR Capital Markets & Co., Research Division: And without maybe, Bruce, getting -- naming names at the FDA, could you give us a sense as to what level you're at, is it sort of C-Suite level, the analogue of that or...

Yes. I think we've -- the way we'd characterized this before is we're at the first supervisory review level, meaning this is the first time we've gone back to a group that's different from the group that originally made the decision. So our first appeal, if you will, was to ask the group that made the original decision, did they want to make a different decision? We're now up a step on the ladder from that.

Our next question will come from the line of Jason Gerberry from Leerink Partners.

Just 2 for me. First one, Defitelio. Based on your more recent meetings, just kind of curious what the outlook is for the prevention indication. If there's anything encouraging, where there might be a potential path forward on the basis of the completed study? Or if your thought is still that, that would require another clinical trial? And then, I guess, just as you launch Defitelio in more European markets, just wondering if the pricing has been consistent with the early launch markets.

Yes. So, Jason, I'll take the first part of the question. So just to be clear, the conversations we've been having with FDA relating to a near-term submission are for the treatment of severe VOD. We are not, in any way, suggesting existing clinical data would get us or them to a prevention indication and we're exploring what additional clinical work we'd like to do in that regard, but that's really a separate discussion. I want to be very clear about that. On pricing, maybe I'll have Russ address that.

Yes, Jason. We'd established EUR 426 as the pricing that we had seen initially. And we are continuing to see good consistency there throughout different countries, so pretty much holding the course.

Our next question will come from the line of Gregg Gilbert from Deutsche Bank.

Going back to the dispute resolution, Bruce. The news you expect to hear by year-end, could you bucket that first in terms of the possible outcomes? And then on the CBM process, which I'm not as experienced with, can you talk about how that might affect the legal process, if at all, both the process and sort of the time line in the legal process as it relates to the CBM process?

Yes. So the bracketing of different outcomes for the current phase of dispute resolution could be anything from they completely disagree with all the arguments we're making, and it's -- they're not moving a bit from anything they've said historically, to they completely agree with us or anything in between. And I don't think we have a basis to know where we'll end up there. In terms of the covered business method situation and how that dovetails in with litigation, that's a complex question. In the litigation we're undergoing right now, we're obviously arguing that ANDA filers, and you're probably referring to Roxane in this particular case, infringe patents we have. Those are pursuant to be a valid patents right now. ANDA filers would obviously argue in their defense that either they don't infringe or that the patents are not valid. If there's a decision which I think I described in my earlier remarks as being as early as the first quarter of 2016 that they both decided to review, completed the review and found those patents to be invalid, then we'd obviously no longer be able to argue -- argue that particular case...

Isn't that part appealable?

Hang on one second. Let me just finish up. Remember that in the Roxane litigation, we previously disclosed that we bifurcated the case, and the piece relating to the distribution system-related patents is staying as of now.

Our next question will come from the line of Jessica Fye from JP Morgan. Jessica M. Fye - JP Morgan Chase & Co, Research Division: Two for me as well. Just as we think about the timing of those JZP-110 trials, I think you mentioned you've begun start of activities here ahead of the planned Phase IIIs and are producing trial material. I guess, just given that we've had the Phase II data, my question's on -- about timing. Have you finalized those Phase III trial designs at this point? And if not, is there some special complexity we should think about here? So basically, are these trials likely to start early in '15 as opposed to later in the first half? And then also, is that trial material a gating factor for shortening the Phase IIIs? Or are you really all set there? And second one is just the low end of your Xyrem guidance at this point, would you characterize that as conservative? It looks like it would imply a deceleration in growth.

Yes, Jessica, thanks for the questions. On JZP-110 trials, we did have an end of Phase II meeting with FDA over the summer. We did share our plans, got good feedback from FDA and feel we definitely understand what those trials look like. Is there any piece of that where we're still dotting Is and crossing Ts? Maybe, but I think substantially, we know what those trials look like. In terms of timing, early or late in the first half of next year. I'll just say our guidance at this point is first half of next year. Don't want to be more specific than that. Is clinical trial material gating? Yes, it is. We need the materials to do the trials. I point that out just to make sure you know what we're currently working on. We don't foresee a problem with that. But yes, we need to complete that to get those trials going. And on the Xyrem guidance, I wouldn't characterize our guidance any differently than I usually do, which is we give guidance that's intended to give you a sense for where we think the range is on average. I think we want to be right, and we don't want to come in at the low end or below our guidance. So if that means it's a little conservative, it's a little conservative. But we typically give a lot of them at the end of the range for a reason, which is it is possible. Not necessarily probable but possible.

Our next question will come from the line of Irina Koffler from Cantor Fitzgerald. Irina Rivkind - Cantor Fitzgerald & Co., Research Division: As we're heading into the new sign-up period for the health care exchanges, I know we had some issues last year, disruption in the first quarter on Xyrem. Do you anticipate that these issues have been ironed out at this point? That's question one. And then the second question is about Erwinaze. Do you foresee any potential competition to Erwinaze from the ERYTECH product that's being filed in Europe or T-cell immunotherapy approaches that are a little bit earlier in development?

So, Irina, let me have Mike Miller handle the first part of your question.

Sure. Thanks, Bruce. The Q1 payer activity that you see is driven a lot by the new enrollments, plan design, things of that nature that are not Xyrem-specific; they are environmental and they will occur again. With respect to SDS, however, we have seen improvements in processes and operations. We have increased our staffing. We think that SDS will perform better in Q1 '15. And as I said earlier, our job is to make sure that we can get timely dispensing for both providers and patients, and that's our goal.

And on the second part of your question, which is -- I'll describe broadly as a potential evolution in treatment options in ALL, let me have Jeff talk about that a little bit.

So there is activity in this area, and there are areas of still unmet need. Beginning with the first part of your question, the ERYTECH product GRASPA, which is -- for those who may not be familiar with, it's just asparaginase encapsulated within a red blood cell, which presumably reduces the immunogenicity and increases the half-life, that's something that's been studied mostly in Europe, mostly in France, somewhat in Belgium. There, their space [ph] have been up against native E. coli-based asparaginase, which is rarely used and set off here in the U.S. I don't think there's a product that you can get now. So it seems -- it's very difficult to kind of assess where it will fit into somebody's regimen as they move forward with that. The other -- the T-cell mediated approach is either these are panitumumab or the CAR-T approaches are interesting. These are right now being focused mostly on the relapsed/refractory group, in the older age group, where using the asparaginase is a little bit more difficult. And some of the results are pretty impressive. And so this is something we'll watch over time. They each have their pluses and minuses. But again, some of the results have been pretty nice. Irina Rivkind - Cantor Fitzgerald & Co., Research Division: And then just one last one. Would you be able to comment on what exactly the FDA asked for in terms of the share ground dispute?

Yes. Just one more comment on ALL before I move on to that. I would just say as a reminder to everyone that in the pediatric ALL treatment, right now, the accepted protocols are very effective in terms of the efficacy of the regimens. And so talking about significant advances in ALL therapy, you're generally not talking about that sort of starting regimen. You're talking about relapsed or refractory patients, older patients. So I just want to make sure that we put Jeff's comments in context. On the second -- on your follow-up question, I won't ask exactly what data they asked for in the -- in their request for additional information other than to point out that, that was really part of our ongoing deemed REMS to REMS approval process. That's separate from the single-shared system discussions that are ongoing that started, as most of you will recall, early in 2014. But this -- those are sort of 2 separate processes.

Our next question will come from the line of Gary Nachman from Goldman Sachs.

Bruce, just to follow-up on that last point on Xyrem with the shared REMS process. Just give us a little bit more in terms of how that has been progressing in terms of discussions with the generic companies. Is that even feasible at this point? But it sounds like they have still been moving forward. And then from that, SG&A came down sequentially in 3Q. Why is that with the DTC campaign that you had over the summer? Should it pick back up? And what are some of the key drivers of SG&A we should think about moving forward over time?

Yes, thanks, Gary. On the first line, I really can't provide more color than -- other than to say that process for single-shared system discussions, which include us and the ANDA filers, is an ongoing discussion. I think I've said in the past, these are complex discussions, I think I'd pointed out that we've been involved in other single-shared system discussions outside of sodium oxybate and those have proven to be complex and lengthy. So I wouldn't read anything in particular into the time. Is it possible to get there? We'll see. It often has been in other situations. If not, there are procedures for what FDA can do in those instances. But I think the preference is, in general, to start with an effort to identify whether there's a single-shared system that, in fact, can work. On SG&A sequential, let me hand that over to Matt.

Yes. Gary, much of the discrepancy in the third quarter in terms of lower SG&A relates to timing-related factors. So we do expect, again, based on our overall guidance for the year, a pickup in SG&A in the fourth quarter. Some of that is on various sales and marketing initiatives in the third quarter that are not related to general awareness. And much of it is also in a variety of G&A-related projects that really span across all of the G&A functions; legal, IT, corporate affairs, met affairs in a few places. So it's actually not any one thing to point to other than we had some delayed spending in the quarter that again, we anticipate picking back up here in the fourth quarter. So we would reiterate that we'd expect SG&A again for the year to be pretty similar to 2013, as we continue to invest in growing our business this year, as we stated earlier in the year.

It's okay. And then I know you're obviously not giving guidance for 2015, but could you point to maybe some of the areas that you've earmarked that you might increase some of your spending in terms of sales and marketing, some of the initiatives that you're thinking about?

Okay, Gary. For the third of your 2 questions, I'll hand it over to Matt.

Thanks, Bruce. Thanks, Gary. So we probably won't get into a lot of specifics about what we're going to see in 2015 at this point in time. Is it possible as we continue to evaluate our general awareness campaign that we invest money there? Yes, but we're still in the middle of setting our numbers for 2015 and aren't really prepared to give really specific guidance at this time.

Our next question will come from the line of John Newman from Canaccord.

Just a question for Bruce. So Bruce, the comments that you made earlier in the call regarding Erwinaze almost sounded like you're feeling more confident in terms of, really, fortifying the manufacturing process there as well as expanding the capacity. I just wondered if that's the case. And also how the progress is going in terms of switching over to a new manufacturing process there in the future?

Yes. Thanks, John. On the Erwinaze supply situation, this is something we are very focused on. We're aware that this is a critical drug for the patients who need it, and we do not want to be in a situation where we are unable to supply. And our efforts working together with our supplier are to build up inventory levels over time, do things that make that manufacturing process more robust. At this point, we are talking just about working with them. I'm not intending to signal that we've got some separate supply coming online. This is working with our existing supplier in that regard. Just to be perfectly clear with everyone. We've pointed out; we are not running at a point where we have sufficient inventory levels to handle a big manufacturing problem. Were we to not be able to use one of the batches that's manufactured, that would be a serious problem. And that's why we are focused on doing everything we can to have a more robust, meaning certain process, that every batch we make is, in fact, a quality batch that can be used in the marketplace, but also, ideally, to put ourselves in a position where you've got inventory on the hand to buffer against anything that could go wrong, which is, of course, what we do for other products and what I would think is standardly done in our industry. So we're focused on it. We're working on it. We have a lot of good people, both at Jazz and our supplier working on it. But I didn't mean to suggest more confidence. I just mean to suggest we're focused on it. We are making progress, but we're not at a point and we won't be at a point in the near term where we have such an inventory level that we won't continue to be concerned and focused on this.

Our next question will come from the Jonathan Eckard from Citi.

And I'll only ask one to bring down the average. So for JPZ-386 (sic) [JZP-386], I think you guys have done quite a bit of work on different Xyrem formulations or sodium oxybate formulations in the past. And would it be safe to say that when we see the data, the PK will be fairly self-explanatory of what it is? But does that always answer all the questions regarding the appropriate PD? I'm just trying to understand how we need to -- what we need to assess in the data for both yours, JPZ-386 (sic) [JZP-386] as well as competitive formulations when they start coming out?

Yes, John, I'll make the comment that I made before. So I don't mean this to be new to anyone. But Xyrem has been studied as twice-nightly dosing in significant pivotal clinical trials. That's the basis for the approval we have and the treatment paradigm that exists. Changing that delivery profile and knowing exactly what that will do in terms of efficacy, in terms of safety, is not something that's been studied in any significant way, certainly, in any determinative way in the past. So do we feel like we are as educated as anyone on the planet in terms of what we want to accomplish and what it might do in patients and benefits and risks and how we think through all that? Absolutely, we do. Does that mean we have all the answers as if all the experiments have been done and all the clinical work have been done? No. We don't have those answers, and no one has those answers. I hope that helps.

Our next question will come from the line of Marc Goodman from UBS.

I was hoping we could talk about Defitelio a little more. Just give us a flavor for -- as the countries came on, was it geographical expansion that drove sales? Was it more penetration in the areas where you were? Just give us a flavor for that. And I mean, when you look at the sales, obviously, last quarter, 20; this quarter 19. I'm seeing your guidance, which is basically not even 20 in the fourth quarter. Can you just give us a flavor for how you're thinking about this?

Yes. Yes, Marc, I would just say it's a complex process to launch this product. I can't say it's just geographic expansion because remember, the product has been available in generating revenues on a named-patient basis in many of these markets historically. So it's not your typical launch where each time you start selling in a new territory, you're realizing revenues for the first time. There's an impact of what the price is in each market where we're selling. There's an impact of how the reimbursement system works. And there are also impacts as we transition or can be impacts as we transition from named-patient basis over to on approved product with improved reimbursement that's being commercially promoted. So there can be some disruption during that process. So what we've tried to do, starting with our initial guidance for 2014 and in all of our commentary about this launch is really focused people on the fact that we are taking our time to get this right over the balance of this year and into next year, honestly, to position this product for creating the value we think this franchise will be over time, starting within the E.U. and obviously, separately, we'll talk about the U.S. So this is a very deliberate effort. It will take some time, but particularly given that we're doing that named-patient basis over the commercial transition, it's worth taking the time to get it right. It's not as though that product is not available to the critical patients who need it in those markets before we do that transition. I want to make that clear. We're very focused on making sure patients get the benefit of the therapy. But that's why this is not your typical stair-step, add a new market, get new sales kind of launch. And in terms of the progression quarter-to-quarter, I think we're less concerned about exactly what that looks like than the overall trends. I would say we see that in our Erwinaze business a little bit, where we'll see some bumpiness quarter-to-quarter that we don't think necessarily reflects any true underlying trend that can be more related to ordering patterns or just how the disease presents and what is an orphan indication in very small number of patients.

Our next question will come from the line of Douglas Tsao from Barclays.

Just maybe, Bruce, you could provide a little color in terms of the 20% of patients who are actually getting denied reimbursement for Xyrem. Are those patients being -- are those patients who are potentially being treated for an off-label use? Or are they being sort of a step at it for them to go on to stimulants first and do you see evidence that they eventually make it back on to Xyrem, just given the fact that we know that stimulants don't have terribly good efficacy? And then, I guess, as a quick follow-up question, just obviously, it seems like by many of the metrics that you track, are there a lot of really strong indicators in terms of the DTZ campaign in terms of disease awareness in those initially 8 cities. At what point would you think about taking it more broadly? Or do you think those -- were those markets sort of the ones that, sort of, for whatever reason, had the best characteristics, and that you're going to perhaps wait a little bit before going, sort of, national, if you will?

Okay. I would just say on the first part of the question, I don't know the drug out there that's got a 100% non-denial rate. I think you hit a couple of the things that probably do factor into that, including people for whom the drug may not be appropriate therapy, in which case, it's a good outcome, honestly, that it's not being paid for and not being dispensed. So that's not a number we would ever expect to be 100%. I'm not sure it would be a good thing if it were 100%. Mike, if you want to add anything to that, feel free. And then I'll let you comment on how we evaluate the disease awareness, which I'll just point out for people is not really a direct-to-consumer campaign. We're not promoting our brand to consumers, but talk about how we'll elevate that data and make a decision on potentially broadening the campaign.

Sure. So the approval rate of the 80% has been actually pretty consistent throughout the year, and we're pleased with that. The denials can range from a number of reasons that you've mentioned, as well as even pushing back on requirements for a sleep test, and that they see the sleep specialist, and there are some step therapy in some of the plans and so on. So there's a variety of reasons. They can also be appealed. When you do get denied, there are appeal processes that are done and medicals of -- a letter of medical necessity and so on and so on. So there's a range of reasons for denial, and I think we focus on the positive side of the coin, which 80% getting approved is, I think, important for patients and providers. So we're quite good with that. And so on the disease awareness, as Bruce said, this is really -- the long-range goal is to increase the diagnosis of narcolepsy. We're looking at the claims data that would reveal that. There is a lag to that data. We're pleased with the initial interest. And based on the website and the ESS testing and so on, we're pleased with the outcomes that we've seen so far. Ultimately, we need to see the claims data. And I think that is what we hope to get here in the coming quarter, and we'll see what it says.

Our next question will come from the line of John Boris from SunTrust.

First question on JZP-386. It certainly sounds like there could be some data readouts. Can you maybe possibly give us an idea of what we might see going forward here out of the European study that's ongoing and the timing for that? And then the technical hurdles; quite frequently, some of the products that have been deuterated are in very low milligram potencies. In the case of Xyrem, we're dealing with anywhere between 6 to 9 grams of drug. Does the agency have any concerns? I think you articulated, Bruce, that, obviously, there's a fine line between maximizing efficacy within that once-daily dose and obviously, the safety of the patient in ensuring that they wake up with the prescribed period of time, that you are deuterating the compound and is the agency have any concern over the amount of deuteration that could be given to a given patient because of the cramp [indiscernible]? And then second question, just has to do with the Federal Trade Commission. Have you had any dialogue with the FTC, and have they requested any information on your distribution mechanism?

So on the first part of your question. I think you're asking would regulatory agencies have any particular concern about the absolute quantity of the deuterium-modified compound? And I would say no. and that doesn't mean to say it's not something they would look at, but I would say that's something you could imagine has been discussed in early conversations as part of us thinking about how to do clinical work. So I would take that off your list of things to have high on your priority list. On the FTC, not something we'd really comment on. If we had something to say there, we would have said it, but no more comments there.

Our next question will come from the line of David Maris from BMO Capital Markets.

Bruce, on JZP-110, how many patients do you think you'll have to study as part of the Phase III program? And given that you mentioned earlier that the trials will really be starting up later this year and early next year, should investors be thinking about a big step-up in R&D spending? Or is this going to be managed as a gradual increase? How should we think about that?

Yes, good question, David. Let me take the second half of it first, and I'll hand it back to Jeff for sizing of the trials. We have given some general commentary about the size of the Phase III program for JZP-110. We've estimated it's about $100 million investment over time, 2014, 2015, 2016. We've said we want to submit in 2017. We think the bulk of that spending happens in 2015 and 2016, but we haven't, obviously, given specific R&D guidance for 2015 alone yet. Jeff, you want to talk a little bit about size of the Phase III program?

Sure. So we have some good Phase II data that were talked of in planning the sample size for the various studies. We know the types of effect sizes we would hope to get. And so we're pretty clear on how to do that and narcolepsy studies tend be smaller than the OSA studies. But what we'd also have to do is to achieve the total number of exposures that is determined by ICH guidelines, and that's going to be one of the factors that are going to play into the total number that we have. So it'll be in excess of what goes into the Phase III pivotal trial there'll be a safety study, which will be able to provide us with some additional exposures.

And our next question will come from the line of Oren Livnat from JMP Securities.

Just a couple. On JZP-110, how much of a potential game-changer, one way or the other, is DEA's scheduling for that product down the road? And at what point in the development time line might you get some indication where that could shake out? And also, maybe this is a no-comment, I'm going to get on this. But on the shared REMS negotiations, can you at least characterize whether you are discussing with all filers, potential shared REMS and one someone new like Watson's filed and certified, do they get invited to the table? Or is this just currently a first-filer negotiation?

Yes. Let me take the second question first. Yes, in general, the discussions are between the brand company and any ANDA filers. I will point out that the Watson Paragraph IV certification was very recent. So they do get added in over time. That would be our expectation. On the first question on scheduling of JZP-110, I do think that's important to products in this space. Typically, the assigning of a schedule happens at the very end of the process. That doesn't mean we don't have a look at relevant data that would inform that discussion earlier on in development, but as a matter of fact, I think the actual final determination happens late in the process. We've said, in the case of JZP-110, we really like the product's profile, both in terms of the efficacy. We've seen in the 2 Phase II trials the strong effect it has on excessive daytime sleepiness in these patients, where that is a critically important thing to them. But I think we've also commented that we really like what we've seen from the tolerability side and I'll just say safety broadly, not just based on Phase II data, not larger Phase III trials, but I'll remind you the product has been in development in other indications earlier in its history. So we do have a fair number of exposures to base our -- at least, our data thus far on. So part of the reason we're very excited about JZP-110.

And I'd like to turn the call back over to Kathy for closing remarks.

Thank you, Crystal. Thank you again for joining us today. We're planning to attend the Credit Suisse, the Stifle, the Piper Jaffray and the NASDAQ conferences in the fourth quarter and look forward to seeing many of you there. This will now end the call.

Ladies and gentlemen, that concludes today's conference. You may now disconnect. Have a great day.