Jazz Pharmaceuticals plc (JAZZ) Q4 2012 Earnings Report, Transcript and Summary

Welcome to the Jazz Pharmaceuticals' Year End 2012 Earnings Conference Call. Following an introduction from the company, we will open the call to questions. I will now turn your call over to Ami Knoefler, Executive Director of Investor Relations and Corporate Communications at Jazz Pharmaceuticals. Please proceed, ma'am.

Thank you for joining the Jazz Pharmaceuticals PLC Investor Conference Call. Earlier today, we reported our fourth quarter and year end 2012 financial results and provided 2013 financial guidance in the press release. The release is available in the News and Events section of the company's website. With me for today's call are Bruce Cozadd, Chairman and CEO; Kate Falberg, CFO; Russ Cox, Chief Commercial Officer; and Jeff Tobias, Head of R&D and Chief Medical Officer. I'm also pleased to welcome our new Vice President of Investor Relations, Cathy Latrell, [ph] who will be hosting future investor calls as I transition to a new role in Corporate Communications and Advocacy. Following some introductory remarks, we will the open your call for your questions. Please note that certain comments we make on this call constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to future events, future financial results, growth potential, financial guidance, pipeline opportunities, future regulatory and intellectual property matters and other statements relating to our plans, expectations and intentions. These forward-looking statements involve numerous risks and uncertainties that could cause our actual results to differ significantly from those projected, including risks and uncertainties associated with our ability to maintain and increase sales of Xyrem, the potential introduction of generic competition to Xyrem, potential change or increased regulatory restrictions on Xyrem, the challenges we face in developing and protecting our intellectual property, our need to obtain appropriate pricing and reimbursement for our products in an increasingly challenging environment, ongoing regulation and oversight by U.S. and non-U.S. regulatory authorities, our dependence on key customers and sole source provider -- suppliers, excuse me, the difficulty and uncertainty of pharmaceutical product development, clinical success and regulatory approval and our ability to identify and acquire in license or develop additional products or product candidates to grow our business. These and other risks related to our business are detailed in our SEC filings, including under the heading Risk Factors in our quarterly report on Form 10-Q for the quarter ended September 30, 2012, and in our annual report on Form 10-K for the year ended December 31, 2012. Our SEC filings and reports are available on our website. We undertake no duty or obligation to update any forward-looking statements contained on this call as a result of new information, future events or changes in our expectations. On this call, we discuss several non-GAAP financial measures, including adjusted net income, adjusted combined SG&A and R&D expenses and adjusted earnings per share. We believe that these non-GAAP financial measures are helpful in understanding our past financial performance and potential future results. They are not meant to be considered in isolation or as a substitute for comparable GAAP measures. A reconciliation of GAAP to adjusted financial measures is included in our press release issued earlier today, which is available on our website. We expect to file our Form 10-K for 2012 shortly. I'll now turn the call over to Bruce.

Thank you, Amy, and good afternoon, everyone. Thank you for joining us. 2012 was truly a transformational year for Jazz Pharmaceuticals. We completed 2 major transactions that broadened our product portfolio and enhanced the scale and capabilities of our company. We aligned our commercial operations with the portfolio and divested our non-core women's health business. We expanded our revenue base from continuing operations to $586 million, more than double our 2011 revenues, and importantly, we delivered a record adjusted net income of nearly $300 million, reflecting the significant top line growth and attractive margins of our business. 2013 is off to a strong start. We plan to continue the momentum in our business by growing our key products through continued solid execution in all of our business units and by making selective investments in new initiatives, which I'll talk about in a minute. We'll also continue our focus on corporate development with a goal of adding additional specialty products to our portfolio. Let me update you now on some of the initiatives related to the 3 products in our current portfolio that we believe have the highest growth potential, Xyrem, Erwinaze and Prialt, as well as our planned investment in R&D and corporate development to support our growth strategy. Kate will then review our results for 2012 and provide our financial guidance for 2013. Xyrem remains a key driver of our growth. In 2012, we achieved a record $379 million in revenues, reflecting an increase of 62%. We were pleased to achieve double-digit volume growth for the year, as the average number of active Xyrem patients in the fourth quarter grew to approximately 10,450 compared to 9,300 in the fourth quarter of 2011. This volume growth has come from improvements in compliance and persistence and increasingly, from new patient starts, which we think bodes well for the future. As you know, we've been working to expand the base of physicians who prescribe Xyrem, so the patients with narcolepsy symptoms have a better chance of finding a doctor who will recognize and diagnose the condition and can evaluate whether Xyrem is an appropriate treatment option. We are approaching this goal in a number of ways. We've increased our physician call audience with improved targeting of narcolepsy prescribers. We created Xyrem-only sales force that is focused solely on growing the Xyrem business and we are adding to our medical affairs group in providing more physician education. Earlier this year, as an example, we supported a nationwide satellite symposium led by highly recognized narcolepsy experts, to educate physicians on the underlying pathophysiology of narcolepsy and its symptom presentation. We are also piloting some web-based initiatives, and we are kicking off a multifaceted disease education program known as Narcolepsy Link, which will include additional tools to be rolled out during 2013. I'm also pleased to note that Dr. Jed Black has recently joined Jazz to head up our medical efforts in narcolepsy. Dr. Black is a renowned sleep expert with extensive experience in narcolepsy research, including the original Xyrem clinical trial and most recently, new studies evaluating the burden of narcolepsy. Dr. Black will be representing these data at a number of medical meetings over the next few months, including the American Academy of Neurology, American Psychiatric Association and the sleep meeting of the American Professional Sleep Societies. We've continued to make good progress in resolving open regulatory items with the FDA. We finalized new labeling for Xyrem with the FDA in December. The updated labeling reflects additional information to help ensure that Xyrem is used appropriately, such as stronger warning against its use in combination with alcohol and with other CNS depressants. We've also submitted all data and completed all actions that we believe are required to address the observations in the May 2012 Form FDA 483 and the matters raised in the October 2011 warning letter. We have submitted a request to the FDA to close out the warning letter, but can't predict the timing or outcome of the FDA's review and expected reinspection. Regarding the Xyrem and the litigation with Roxane, you will recall that we recently commenced 2 more cases against Roxane with respect to additional patents that were issued in late 2012. Our initial lawsuit against Roxane remains stayed, pending a court ruling related to potential consolidation of the 3 cases. Regardless of the consolidation decision, the parties will ultimately need to complete fact discovery related to the patents that are at issue in the 2 new cases, conduct expert discovery under all 3 cases and prepare for an eventual trial. No trial date has been set in any of the cases. The complexities of the regulatory matters relating to Xyrem and the introduction of any generic version of Xyrem, as well as the status of our pending lawsuit suggest that it will take time before these issues are fully resolved. In January 2013, we initiated litigation against the second ANDA filer, Emil Pharmaceuticals, triggering the 30-month stay for that ANDA. We remain focused on leadership in narcolepsy and plan to further grow Xyrem sales by continuing our marketing initiative, such as targeting physicians treating sleep disorders while increasing our efforts to educate the health care provider community on the diagnosis of narcolepsy and adding programs to increase patient awareness of this disease. In addition, as announced in our press release today, we have entered into an exclusive license agreement that gives Jazz worldwide rights to develop and commercialize concerts, deuterium-modified sodium oxybate compounds including C-10323. Under this agreement, we have worldwide commercial rights to these compounds, as well as principal responsibility for ongoing development activity. C-10323 is an early-stage R&D program that provides us an opportunity to explore the potential of this molecule and this disease and to further evaluate the potential to provide benefits for patients with narcolepsy. We plan to file an IND later this year. We're also making great progress with Erwinaze. Full year pro forma results exceeded our expectations, and the fourth quarter represented the highest quarter to date in worldwide net sales. We believe the strong fourth quarter is an early result of the ongoing commercial efforts and physician education initiatives we put in place after acquiring Erwinaze in June. At an investor conference earlier this year, we talked in more detail about our strategies to grow Erwinaze, including an increased focus on improving awareness and understanding of hypersensitivity, expanding use in appropriate populations, identification of silent hypersensitivity and selected research initiatives to support long-term growth. Since that update, some important developments have occurred to support these strategies. We have proceeded with efforts to educate the health care provider community about hypersensitivity detection based on the standardized classification for the latest common terminology criteria for adverse events. In December, approximately 350 health care providers participated in an educational series focused on building a greater appreciation for appropriate grading of hypersensitivity. Additional health care provider focused education activities are planned, including those that emphasize the underlying immunological effects of hypersensitivity to support the medical rationale for switching to Erwinaze. And just this month, a commercial assay to measure asparaginase activity has been launched in the U.S. by AIBioTech. Currently, the assay is not part of a broad-based protocol-driven approach to treating pediatric ALL patients, but it has the potential to assist health care providers with identifying patients with silent hypersensitivity. We also continued to strengthen our level of reimbursement support services for Erwinaze. While reimbursement for Erwinaze has been excellent, we are providing new tools to help expedite and simplify the process, including access to reimbursement specialists that can provide a single point-of-contact to support hospital account. Finally, we continue to pursue research and development initiatives to support Erwinaze. Our ongoing trial testing IV administration is enrolling patients and we hope to complete enrollment and have data to report later this year. We are also planning a study in the adolescent and young adult population to begin late this year. This trial will be designed to provide us with information on the use of Erwinaze in this important patient population. We remain confident and enthusiastic about the opportunity for Erwinaze worldwide. Let me comment briefly on Prialt, our non-opioid, intrathecally administered drug approved for severe chronic pain. We have begun making important progress on our long-term growth strategy for Prialt, beginning with the launch of our NAVIGATOR distribution program last fall. As a reminder, perceived reimbursement difficulties were identified in our research as the top reason that physicians do not use Prialt more broadly. To date, approximately 50% of our accounts have enrolled in the new Hub system, which can improve access to Prialt by informing physicians and patients of the available reimbursement options. We continue to believe that there's an opportunity to increase Prialt's penetration in the intrathecal pain therapy market, currently around 3%, and implementation of the Hub as an important first step. Another core area focus for Prialt has been planning for the launch of our Prialt registry in the coming months. The registry, which we call Prism, or patient registry of intrathecal severe pain management, will provide us with additional data on Prialt treatment and outcomes. We're eager to proceed with these projects as they support our long-term growth strategy for Prialt. Another area of investment for our company this year will be to advance targeted R&D projects that supports life cycle management strategies for our products and to develop new potential products that may be added to our pipeline. In addition to supporting line extensions, such as the IV administration of Erwinaze and recently approved Clozapine oral suspension formulation Versacloz, we currently have 2 development products in the pipeline. Asparec, a pegylated Erwinia-based recombinant asparaginase, is currently being evaluated in a Phase I study in Europe. Our U.S. IND filing for Asparec was completed during the fourth quarter of 2012 and we plan to advance the U.S. pediatric study this year. We are also evaluating Leukotac, an anti-CD25 antibody for the treatment of patients with steroid-refractory acute graft versus host disease in a late-stage study that is enrolling in Europe. In summary, we're investing selectively in R&D projects that include line extension for our current marketed products, the generation of additional clinical data for existing products and targeted development of a pipeline of post-discovery specialty product candidates. On the corporate development front, we continue to see the opportunities to inquire or in-license additional marketed specialty products or products that are close to regulatory approval. Although there is competition for business development deals, we continue to believe that our strong balance sheet, existing expertise and specialty markets and strong infrastructure position us well. Finally, let me thank our employees for their dedication and focus on our company mission during a year of rapid change as we transformed Jazz Pharmaceuticals plc and increased our employee headcount from approximately 240 to just over 600 worldwide. We just completed annual kick off meetings for our use of pharma division at our U.S. commercial operations. These groups have great momentum entering 2013. Our R&D organization is rapidly moving to advance our development programs. And finally, the level of enthusiasm among employees for multiple locations and functional areas is strong, and we're excited about many opportunities before us in 2013. Kate, I'll now turn the call over to you.

Thanks, Bruce, and good afternoon, everyone. Beginning with the top line, total revenues for 2012 were $586 million, up $314 million or 115% from the prior year. Total revenues for the fourth quarter were $184 million, up $100 million or 120% from the year-ago period. These increases were due to revenues from products added to our portfolio from our 2 acquisitions, as well as continued strong growth of Xyrem. This year, we expect robust top line growth with total revenues in the range of $805 million to $835 billion, up 37% to 42% on an absolute basis and 20% to 25% on a pro forma basis. We are anticipating continued strong growth from both Xyrem and Erwinaze this year. Net sales of Xyrem were $379 million for the year and $114 million in the fourth quarter, up 62% and 58%, respectively. We were pleased to achieve 11% volume growth for the second year in a row, and we are very pleased with the 13% year-over-year volume growth in the fourth quarter. We do note that fourth quarter growth was positively impacted by having one additional shipping day compared to the fourth quarter of 2011. Our net sales guidance for Xyrem this year is a range of $530 million to $540 million and reflects our expectation of high-single to low-double-digit volume growth, as well as the 16% price increase implemented February 1. Turning to Erwinaze, worldwide net sales were $132 million for 2012 on a pro forma basis and $34 million in the fourth quarter. Remember that Erwinaze was approved by the FDA in November 2011, making year-over-year comparisons less meaningful. This year, we expect strong growth for Erwinaze, with net sales projected to be $155 million to $165 million worldwide. Under the terms of the EUSA deal, if Erwinaze achieve U.S. net sales of at least $124.5 million in 2013, we will be obligated to pay former EUSA shareholders an additional $50 million. U.S. sales have represented more than 3 quarters of worldwide sales. Net sales of Prialt were $27 million for 2012 on a pro forma basis and $6 million for the fourth quarter. As a reminder, the net sales for the year includes $5 million related to a supply agreement that provides Prialt to Eisai for distribution in Europe. We were pleased to see year-over-year volume growth of 13% in the fourth quarter in conjunction with the NAVIGATOR distribution program rollout. Net sales were impacted by higher growth to net deductions. We are not providing specific revenue guidance for Prialt, but directionally, we are expecting to see continued sales growth as a result of the initiatives Bruce outlined. Net sales of our psychiatry products were $76 million for 2012 and $18 million for the fourth quarter. Annual sales increased 7% on a pro forma basis. Our 2013 guidance assumes launch of our oral suspension formulation of Clozapine Versacloz in the summer timeframe and reflects potential near-term generic competition for LUVOX CR. As a reminder, under the terms of the settlement agreement, a generic could launch upon receiving FDA approval. Overall, we are expecting a decline in revenues from our Psychiatry business this year, as a result of generic competition. Adjusted combined SG&A and R&D expenses were $202 million for the full year or 34% of revenues and $60 million in the fourth quarter. Adjusted SG&A and R&D expenses, as a percent of revenues, were the same in 2012 as in 2011, and the growth in expenses was primarily due to the expansion of our business with the Azur and EUSA transactions, as well as increased investments in support of Xyrem, Erwinaze and Prialt. This year, we expect our adjusted combined SG&A and R&D expenses to be $260 million to $275 million, essentially unchanged as a percent of revenues. The growth in expenses reflects the initiatives that we've outlined to grow our existing franchises, anticipated expenses to enhance and defend the longevity of our products and investments we are making to provide for future growth of our business. Turning to taxes. On a GAAP basis, our tax provision for the fourth quarter and full year reflects a large credit from the reversal of a valuation allowance of $104 million against most of our remaining NOLs, credits and other temporary items. This reversal occurred because we determined that we expect to be able to fully utilized these deferred tax assets in future years. This was backed out of our adjusted income. Our adjusted effective tax rate for 2012, which reflects cash tax liabilities was lower than previously expected due to the better-than-expected results of various restructuring and tax planning activities that concluded in the fourth quarter. We now expect our 2013 adjusted effective tax rate to be in the high-teens, which is significantly better than we previously anticipated due to the results of our restructuring and tax planning, as well as better-than-expected results from our evaluation of the availability of NOLs and tax credit from EUSA. The GAAP effective tax rate for 2013, which is impacted by various noncash items, is expected to be in the mid- to high-20s. We currently expect our adjusted effective tax rate to remain in the high-teens range for a number of years. Of course, new products we develop or acquire could impact our tax rates depending on the circumstances. Turning to the bottom line. We reported adjusted net income of $290 million or $4.82 per share for the year and $94 million or $1.53 per share for the fourth quarter. In 2013, we expect substantial growth in the bottom line, as reflected in our guidance, of $355 million to $367 million of adjusted net income or $5.70 to $5.90 of adjusted EPS. It's worth noting that despite the increase in our effective tax rate and interest expense this year, we expect our adjusted net income, as a percent of revenues, to remain very attractive. Our balance sheet is strong as we ended the year just shy of $400 million in cash in investments and a balance of $457 million of debt, currently at a 5.25% interest rate. Because we continue to actively seek to acquire additional specialty products to further leverage our efficient corporate structure and commercial expertise, our current intention is to retain our cash balances and make only the required debt amortization payments. In summary, we think our plans reflect our continued drive to achieve our mission of delivering important therapies to patients while also continuing to create value for our shareholders over both the short- and longer-term. Thank you for joining us on the call today. I will now ask the operator to open the line for your questions.

[Operator Instructions] Your first question comes from the line of Louise Chen, Guggenheim.

I have a few. First one is with respect to your bi-annual price increases. I know you get asked that a lot, but just curious. What gives you confidence that these can continue and where do you think you might start to get some resistance on these type of price increases annually? And then second question is on Xyrem with respect to settlement with Roxane or the other generics companies versus taking a calculated risk on the litigation front. How do you -- strongly do you feel about that? And then maybe last question is just on the prescriber base. As you go broader, where are you today and where could you go and what kind of upside could we see from that?

So this is Bruce. Why don't I let Russ take the question about price increases. You asked it as -- as if it's a sure thing we'll increase prices twice a year. We haven't actually said what will do going forward, so I'll just clarify that. But I'll refer over to Russ your general question about price increases and maybe expansion of the prescriber base, and then I'll come back to take the middle part.

Sure. So in terms of -- if you look at how many of your colleagues have modeled the future going forward in terms of price increases, most of your colleagues has seen this sort of back off over time, so I don't think everybody is thinking that this is a fully sustainable approach for the next several years. I do think that what we spend all of our time thinking about is where do volume and price meet and really spent a lot of time looking at whether there is any impact on current volume as a result of price. From the patient perspective, we actually don't see the prices impacting the patient flow. In fact, we actually are more convinced that we've -- with the suite of services in place that actually address that issue in a very comprehensive way, and we're not seeing price being an issue at patient level. And so while we don't tend to tell you what we think we should do in the future with pricing and we monitor very carefully, we would also say that prior authorizations continue to increase at about almost a 50% rate. And beyond that, we don't see anything changing in the fair [ph] landscape. In terms of additional physicians, we've actually done a great job of targeting about another 1,000 physicians in our call universe that's driven by finding data that tells us where narcolepsy is being treated from a stimulant perspective, from refreshing new databases that we get from the sleep society, and then just ongoing prospecting, having a sales force now that is 100% focused on Xyrem. So we've gone from about a call universe of 3,000 to about 4,000, and that seems to be paying off.

And your other part of the question, which was something about how we view potential for settlement versus proceeding through litigation, a little difficult for us to comment too specifically on that. We continue feel we've got substantial intellectual property protecting our Xyrem franchise, and we note that this is a complex area. We've certainly made our priorities clear, which is to continue to grow our presence in narcolepsy and help more narcolepsy patients, to continue to ensure the continued safe distribution of sodium oxybate for these patients through our restricted distribution system, which we believe does an excellent job in helping patients and protecting the public. But also the ultimately do what creates the most value for our stockholders, and that's how we'll continue to approach that balancing act that you described.

Your next question comes from the line of Greg Gilbert, Bank of America.

I've got a few. First, I think, it's for Russ on Xyrem. Have there been any changes at the payor coverage in 2013 for Xyrem and can you at least comment whether the winds are shifting in that regard in any way? I'll ask them one at a time, if that's all right.

Yes, sure, Greg. So we haven't seen overall change in reimbursement rate. We've typically said that it's around the 80% range, and we continue to see that to be very consistent. I did mention the fact that we are seeing an increase in prior authorizations. Now we've seen that for about 1.5 years now. It was one point in maybe the mid-30s are now approaching about 50% for authorization. And in terms of overall landscape change, we don't see anything meaningful that's actually happening today.

Okay. And Kate, thanks for the new color on the tax rate longer-term, that's really helpful. Have you and the team decided to think about how much you spend in other line items in the P&L now that you have some better certainty that, that rate is lower than you had previously been projecting?

Well, so we gave a guidance for combined R&D and SG&A. And Bruce outlined, in his comments, a number of initiatives where we are making investments. We also announced 1 VD transaction today with Concert Pharmaceuticals. So the short answer is yes. We are continuing to think about the optimal mix of investing for the future versus delivering current earnings.

And then lastly maybe, if I can have Bruce chime in. If you were to commit to significantly larger amount of R&D investment than you just laid for this year, so perhaps longer-term, philosophically, what would you like to be able to share with investors before committing to a much larger R&D spend than you've committed to for this year?

Yes. Well, Greg, I think, we're in the fortunate position of having really good top line and bottom line growth at the moment. Historically, I think, we've been underinvested in R&D in large part because of the company's limited ability to pursue that years ago. So at this point, I think, we can talk about meaningfully increasing our R&D investment without anyone being too nervous about that because frankly, even if we kept it the same, as a percentage of revenues, it's going up. Rather than committing to a defined R&D budget and saying, "What are we going to do with the dollars?" I think, our approach is much more, "Where are there great opportunities to invest R&D dollars?" Particularly, in things that would benefit our existing franchises or be great fits with our capabilities, and then look at how we best pursue those investments. So it's that project-driven decision much more than it is an overall, "Let's just commit a pool of dollars in R&D and then see what we do with it." It's a return on investment proven calculation.

Your next question comes from the line of David Amsellem, Piper Jaffray.

Just a couple. So first on Xyrem. Just remind us what additional patent applications, if any, you have pending and maybe provide some detail on those if you can?

So David, we haven't generally provided a detailed look at that. There has been one allowed, but not yet issued patent, and we've said we had a number of applications pending of different types that we certainly hope would issue in the months and years to come, but we haven't been more specific than that.

Okay. And then second question is on Prialt. Maybe provide a little more color on the NAVIGATOR system and how would you characterize physician receptivity to that system and how it's -- you think it's impacted both usage or -- among doctors and also just the -- how it's resulted in any changes, if any, in the -- in reimbursement paradigms?

Sure, David. I think the best way to think about the NAVIGATOR system at this point is, it's still very much early days. As you know, we launched last November and one of the things that we were very cautious about is, we wanted to make sure that we continue to sort of customized how about there that actually was reflective of what physicians wanted. As you remember, the single biggest objection that we've had from customers on Prialt is just having a better understanding of what the reimbursement landscape looks like. We think NAVIGATOR has done a really nice job of actually telling physicians and patients specifically, exactly, what that looks like. It takes a lot of the questions about risk away. Having said all that, when you launch something like this, you really have to put it out there, take a look and see what the physician response has been. I think we've gotten more of the difficult patients to date, and if you look at the overall uptake, we have about 50% enrollment from the total book of business. So I think we're on a very nice path. I think we're making little tweaks to make sure that we optimize the overall look from a patient-physician perspective so they know exactly what decisions they can make about patients that more based on the medication that's required as opposed to just reimbursement. And I think that as we continue to go down this road, we'll continue to put more and more emphasis on enrollment and put a little bit more rep resources behind making sure that, that happens. We wanted to go cautiously.

Okay. And then one last question if I may sneak in one on the PEGylated asparaginase products. Just give us a sense of what the value proposition needs to be in order for it to be successful? And what you need to see in order to get this to market?

Yes, David, I would say, at first principles, the PEGylation is really designed to provide less frequent dosing to patients. We're now at both an intramuscular injection and 3x a week dosing in the current formulation of Erwinaze in the U.S. and, obviously, there's potential to introduce a product that would be dosed once weekly or once every couple of weeks and provide the same type of benefits to patients. They also mentioned that if it's recombinantly produced that has some advantages, frankly, to us than managing a supply chain being more easily able to adapt to changes and demand potentially with some benefits in terms of the economics of product supply. So let's start with dosing patients as being the most obvious difference as we continue our clinical development it may be that we see other differences that could have importance, including potential hypersensitivity reactions to the Erwinia-derived asparaginase itself. But we'll need to see more data before we say more on that.

Your next question comes from the line of Douglas Tsao of Barclays.

Bruce, I was hoping you could perhaps talk a little bit about the agreement with Concert and what you think the new -- the lead compound, what potential clinical advantages would have over your -- over Xyrem as it exists today? And perhaps a little bit of -- some perspective because it's obviously early stage what -- how you see the potential development pathway?

Yes, Doug, good question and let me turn that over to Jeff, our Head of R&D, to comment a little bit about sort of sodium oxybate and, while it's a great product, it's not perfect and does have some limitations and we're an early-stage program to look at an alternative molecule has, at least, potential to offer some advantages.

Right. So sodium oxybate as we now have a large number of very important therapeutic effects but it's also to some degree constrained by its pharmacokinetic, a very short half life. And so the newly rated [ph] technology has an opportunity to potentially impact that through changes in the metabolic profile. So that's one of the interesting parts about this program is to be able to assess whether or not we can really leverage that effective -- the duration and translate that into something that's clinically meaningful for patients. Development pathway. One of the nice things that we have, that we bring to Concert, this Concert also brings expertise to us is that we have a great deal of expertise here in this area in developing products for narcolepsy, et cetera. So we're going to utilize our expertise to make for efficient path forward acknowledging that this is a somewhat novel compound. So as we go through the development pathway, we're going to always keep in mind an efficient route forward.

Okay. And also, just curious, perhaps a question for Russ on the dedicated sales force for Xyrem, I was just curious what advantages commercially or sort of exactly how is that having an impact in terms of driving volumes for the product? And also I wasn't sure if you mentioned it, if you gave guidance for what your expectations for volume growth were in 2013?

Yes, Doug. So if you characterize what the impact has been, it's been dramatic, and the reason I say that is because we were, at one point, spending about 70% of our time on Xyrem, and about 30% on LUVOX CR. And what that ultimately became is just a huge distraction in terms of downtime for our ability to really prospect. And so we've now really, with 100% focus on Xyrem only and really a restructuring to make sure that we have the right people, in the right places, the right account has led us to, what is now, for the first time ever, true growth in new patients. Whereas before a lot of our growth has truly been driven by changes in persistency and compliance. So we really think this dedicated and highly focused sales force who's now gone to the Atlanta Sleep School of Medicine and are being trained at a very, very high level and can go head-to-head with our narcolepsy experts, has really made a meaningful difference I would also say that we have projected high-single-digit, low-double-digit growth for the balance of the rest of the year.

Our next question comes from line of Ken Cacciatore, Cowen & Company.

I had a question. Bruce, you laid out that clearly the legal situation on Xyrem seems to be taking time or will continue to take time. I was just wondering, from a regulatory perspective, does the FDA take its cues from that kind of, I call it, legal delay? Or are they continuing to progress through and along the that line, have you been asked to negotiate with Roxane on a REMS and, if so asked, does that maybe started the creative process to finally resolving this in total?

No, Ken, on the first part of your question, we don't know whether the FDA's process takes into account what's going on the legal side. I would say, not directly, but you'd have to ask FDA that question. On the second part of your question, have there been conversations between the parties specifically about the distribution system, I'm just going to have to decline to answer that question. That's not a change in response, that's been a pretty consistent response for us -- from us for a while and I expect it will continue to be the response from us. We're obviously involved in ongoing litigation between the 2 parties. So starting to go on record with any conversations that have or could start between the 2 parties that's going to put us in a really awkward position.

Okay. Understood. I guess then on Business Development, just can you give us a sense in terms of anything, either near-term or size, are we seeing assets that we like or just continuing to be pragmatic as we go forward? Can you give characterization on the Business Development processes?

We'll have Kate comment on that.

Yes. So Ken, we continue to actively look. We think we're in the fortunate position where we don't have to do anything, but we'd like to. And we've got the financial capability to pull the trigger when the right thing comes along. But we'll continue to be disciplined, as always. I'd say that there continues to be a number of things that are interesting and the BD group is as active as always in terms of evaluating things.

Your next question comes from the line of Jonathan Eckard, Citi.

If I ask you about the Concert agreement, it sounds like there's other analogues that are part of this kind of family. Does your agreement with them cover any of these other analogues? And also is there any expedited development test for an analogue that's already a controlled substance because it's the same kind of parent drug or is it basically considered a new chemical entity?

The answer to the first part of your question is, yes, in terms of other analogues being included. The answer to the second part of the question, I'd have to say there are some advantages to working with a known compound with known properties in a particular disease and there's certainly some benefit to all the work that's been done in the past. But I think I have to stop short of saying there's a defined expedited clinical development or regulatory pathway because I would say that would be an overstatement.

Okay, great. And then maybe a question for Kate. Remember, the previous discussion, you were kind of -- you're quite optimistic or eager to do more BD. And I know you just made some comments on it, but I think one of the things you said you wanted definitely do before 2013 was over, would this recent Concert agreement qualify for that or are you still eager?

Well, let's ask my boss, if -- does this counts? No, all kidding aside. We did say, and have continued to say, we'd be disappointed if we didn't get another attractive specialty product into the portfolio this year. And so I'd say when we talk about that, we're really thinking things that are either already on the market or near the market. But I'd have to say this one is separate from that.

Your next question comes from the line of Gene Mack, Brean Capital.

Question on Erwinaze and then on Prialt. First on Erwinaze. On the assay, is there any sense from you guys, at this point, based on what you know of how that might -- is there any possibility that it get worked into like a guideline for testing at some point after a certain number -- after a certain amount of data you've been able to compile with the assay? Would you be able to submit that? And then, the other question on Prialt's kind of similar. The outcome's -- or the outcome's database that you're planning, is there a hurdle rate there or a number of patients that you think you might be able to achieve, at some point, where you might be able to publish the data? Or what's the thinking in terms of an endpoint for both those types of things?

Yes. So Gene, let's like Jeff take both the question on the asparaginase activity assay, as well as Prialt registry.

Right. So there's a great deal of interest in asparaginase activity assay as a way of measuring for silent hypersensitivity and we've had conversations with a number of people in this area, including the big cooperative groups, and they are looking into this as to whether -- and how actually to incorporate that into guidelines. So we expect more information on that, perhaps, even later this year. On the registry, the registry is designed so that we will have a constant flow, hopefully, of data that will be of interest for publication. So even as the registry is running, we will have interim analyses looking at a variety of what I think are some really interesting questions as the registry goes forward. So I would anticipate that.

Your next question comes from the line of Amy Fadia, UBS.

I've got a couple of questions. Firstly, on Erwinaze. Could you characterize where you expect the growth to come from, for the product, in 2013? And what I'm looking for is, is it just earlier detection of hypersensitivity or do you expect some usage in the adolescent population as well? And then just a connected question here on the assay. The assay that you talked about, was that launched specifically for ALL patients? And was specific to pediatric patients or a broader population? And then I've got 2 other questions.

Okay, Amy, let me have Russ take the first part of the question on sources of Erwinaze growth in 2013.

We have to really look at 3 areas that we expect to see growth coming from Erwinaze in 2013. We're still making progress in existing pediatric protocols in terms of identifying hypersensitivity reactions and we've seen some good progress through the end of last year, and so we think that that's still an area for growth that we will continue to focus on in 2013. We also believe that the young adolescent, or AOA population, continues to represent some potential upside for the brand during 2013. And as you mentioned, we do believe that, with time, the opportunity for Xyrem hypersensitivity will be incorporated in the potential feature protocols and that, over time, that will outline value as well. So those are 3 areas that we're expecting 2013.

And Jeff, maybe you could comment on the use of this assay and where's it directed?

Right. So the assay is really a generic asparaginase activity assay. So it measures the activity of Oncospar, of the Native E. coli, as well as Erwinaze. So it's really meant to be useful as kind of a therapeutic drug monitoring, as well as a way of looking at hypersensitivity and of interest of the recent publication that came out that showed when you do individualized therapy based on monitoring, you can see better outcomes. So this is really beginning to become, I think -- it's going to become standard of practice, if you ask me, going forward. But having the ability to have an assay like this allows people do those type of approach.

Okay, great. So the 2 other questions are really on the Xyrem franchise. One is the volume growth in the fourth quarter was close to 13% and that doesn't really change if I take out that one extra day. Why wouldn't that double-digit growth continue? Or do you expect to see a little bit of a slowdown because that's kind of what your guidance points to? And then just secondly, on the asset that was acquired today on the C-10323, do you have plans to develop it outside U.S. as well, because it even sounds like you got worldwide rights.

So as it relates to Xyrem volume growth just a reminder that the third quarter was 8.7 and then fourth quarter was, in fact, 13. Having said all that, what I have shared with you is that, we've seen a change in terms of where the growth is coming from. It's not just compliance and persistency that's driving growth. We actually see new patient growth which we think does bode well for future volume. So hard to say whether we're going to see something different in terms of a current growth rate. We've seen high-single digit, low-double digits now for quite some time. The fourth quarter was obviously a very good quarter.

And then on your question about the C-10323, that is a worldwide deal. As you know, Xyrem itself is not commercialized in all markets around the world but is certainly available in markets outside the U.S., including, through our partners, UCB in Europe and Valiant in Canada, so we do think there's an opportunity assuming development moves forward all the way through to the market to end up with a product that would be marketed broadly.

Your next question comes from the line of Michael Schmidt, Leerink Swann.

I just have 2 quick ones. One on Prialt. I think in the past, you've been talking about potentially trying to modify the label of some ongoing work. Could you please update us on these activities? And then, secondly, on the Concert pharma product, what is the expected IP protection to look like on that product and given on the PK profile, are you envisioning this to be a product that could potentially eliminate the second deal [ph] that Xyrem currently has?

Let me have Jeff take the first part of the question on Prialt and label.

Right. So currently, there aren't any specific activities going on to address the label although we're always looking at potentials to be able to use additional data both either to support changes in the data or to support the use of the product. So again, hopefully that answers your question.

And then on your question about the Concert technology and product candidate, certainly, this is novel work they're doing and we would absolutely expect significant IP protection around this program. Could it eliminate a second dose? I think, Jeff characterized this correctly when he talked about a different PK profile moving away from the current short half-life of sodium oxybate and some of the opportunities that might provide one of which worth exploring would be the potential for elimination of the middle of the night dosing for Xyrem. We don't know enough to say with confidence that, that's doable, but certainly, more possible with this approach than the existing indiscernible].

Your next question comes from the line of Bill Tanner, Lazard Capital Markets.

And Bruce maybe these are for you or for Jeff, I'm just a little bit confused in terms of the development path forward to contemplated that bioequivalency testing would not be a viable path?

Yes, Bill, I would say, way too early for us to be talking in detail about clinical development and regulatory pathway forward. All we've said so far is we're going to do an IND later this year and start our efforts and -- to the extent we continue to move this forward, we'll obviously provide more color, but no answer to that question at present.

Okay. And so I'm not that familiar with the compound. Jeff, would it characterized as like a prodrug or an analogue?

No. It's actually -- maybe an analogue in that you're replacing some hydrogen atoms with deuterium atoms.

Okay, Fair enough. And then just a question for Russ, just looking at my patient model, it looked like the patient adds in the fourth quarter, I guess, was a historic high. And if I think about the revenue run rate going forward and we do have a somewhat modest price increase baked in and beginning in the fourth quarter, it looks like you'd almost have to have a fairly significant deceleration of patient adds on a quarter-over-quarter basis in 2013 to hit that, and I know that you guys historically provided some very reasonable and beatable guidance at least at the outset, but how should we think about sort of the trajectory, going forward, if it -- I appreciate that it's hard to know with great clarity but assuming that the effort that you guys are making are not sort of at the end of their lifespan?

Bill, this is Bruce. I'll take that. Just to clarify and, if we didn't say it clearly before, let me say it clearly now. The guidance we provided for Xyrem revenues for this year is at its current price, which does reflect the February 1st price increase. On the other part of your question, I'm glad you're following us closely. I don't have your model up in front of me but, I think, your general comment about new patient starts is a good comment to make and you probably heard us in this call and maybe in the call before this one, emphasize more as the source of growth, new patient starts as opposed to -- in prior calls when I think we're much more focused on improvement and persistent and compliant. So does that mean we know exactly what's going to happen each quarter for the next 4, 8, 12 or 16 quarters? No. But we certainly think that the source of growth coming from the patient starts has the potential to be a more sustainable source of growth over the longer term.

Fair enough. And then I had a -- I guess, one last question for Kate. Just as it does relate to the guidance thinking about the product specific guidance. I'm thinking about the product-specific guidance. So I guess practically speaking what's most important is Xyrem and Erwinaze. As we think about over the balance of the year and it may be a hard questions to answer is that, is the Erwinaze number, it's kind of tied, is that unlikely to be that conservative, you think, over the balance of the year? And if there's a delta, it's going to more from Xyrem potentially either from changes in price or changes in volume growth? Or do you guys feel pretty comfortable with that number, I mean, assuming that you're going to give a number that you think is definitely beatable, but I'm just trying to understand -- would you potentially see much upside to that? Apologize for [indiscernible] the question.

I'd characterize our guidance as reasonable and also recognize that it's early in the year so we're optimistic for strong growth for both Xyrem and Erwinaze, as we said, and I don't think I'd want to get into characterizing which one of them is -- which guidance was more conservative than the other. I think we tried to give reasonable guidance for overall revenues and for both of our lead products.

And if I missed it, just on the Concert deal, was there an upfront payment that was made and is that in the R&D guidance?

So there will be a moderate-sized upfront payment. The amount was not disclosed, and our guidance does reflect the Concert deal.

Your next question comes from the line of David Morris, BMO.

You and others have mentioned that you're in a good position for not needing a deal for the top line or the bottom line, but you'd still would like to do more deals, so can you talk a little bit about the "why" of that. So obviously, the ultimate "why" is to make more money, but if you could talk a little bit about the priorities for deals, is it to diversify the revenue or to keep sales force busy with -- in certain therapeutic categories, so what's your sweet spot for deals that you're looking at? And please don't say CNS, by the way.

Okay. I would say, David, that the primary driver for interest in additional business development here is that we think we have the opportunity to build on the success of the company right now in our area of expertise, which we think is commercializing the specialty products that require a more consultative stele, more medical education, reimbursement expertise. We think we can do that well and we're in the fortunate position of having both the infrastructure that we think we can absorb that, as well as the financial wherewithal to, in fact, go out and acquire assets like that. I -- and as we look at each new potential asset, we are really doing a return on investment analysis. We're looking at whether investing in that opportunity is attractive financially as well as strategically. That is different from saying, let's diversify our top line by going and buying different revenue streams. I certainly will point out that the 2 significant acquisition transactions that we did in 2012 did have the effects of diversifying our revenue stream, but I think about this more as us being on offense than defense. We're trying to go out and invest our capital in ways that make sense strategically and financially to create returns for our shareholders rather than saying, let's just change the profile of our revenue line by adding additional products.

You have no further questions at this time. I would now like to turn the call over to Ami Knoefler for closing remarks.

Thank you, Julie. In closing, a reminder that Jazz will be attending and presenting at 2 upcoming financial conferences in March, the Cowen & Company 33rd Annual Health Care Conference in Boston and the Barclays Global Health Care Conference in Miami. We hope to see many of you at one of these conferences. Thanks, again, for joining us today.

Thank you for joining in today's conference. This concludes the presentation. You may now disconnect. Good day.