Good morning. My name is Melissa, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen Idec Third Quarter 2011 Earnings Conference Call. [Operator Instructions] Ms. Kia Khaleghpour, you may begin your conference.
Thank you, Melissa. Welcome to Biogen Idec's Third Quarter 2011 Earnings Conference Call. Before we begin, I encourage everyone to go to the Investors section of biogenidec.com to find the press release and related financial tables, including a reconciliation of the non-GAAP financial measures that we'll discuss today. We've also posted slides on our website that follow the discussions related to this call.
As usual, we'll start with the Safe Harbor statement. Comments made in this conference call include forward-looking statements that are subject to risks and uncertainties. Words such as believe, expect, may, plan, will and similar expressions are intended to identify such statements. Actual results could differ materially from our expectations, and you should carefully review the risks and uncertainties that are described in our earnings slides, earnings release and in the risk factors section of our most recent annual and quarterly reports filed with the SEC. We do not undertake any obligation to publicly update any forward-looking statements.
Today on the call, I'm joined by Dr. George Scangos, Chief Executive Officer; Dr. Francesco Granata, Executive Vice President of Global Commercial Operations; Dr. Doug Williams, Executive Vice President of Research; and Paul Clancy, Executive Vice President of Finance and Chief Financial Officer. We'll also be joined for the Q&A portion of the call by Dr. Al Sandrock, Senior Vice President of Development.
Now I'll turn the call over to George.
George A. Scangos
Okay. Thanks, Kia, and good morning, everyone. We had a very productive third quarter and several exciting announcements during the month of October as well. Our financial performance was excellent as our products with TYSABRI continued to do extremely well. Our pipeline advanced substantially, led obviously by BG-12, but also including significant advances in many other portfolio compounds, both early and late. And while not so visible from the outside, the company is executing extremely well and is much more effective and efficient than it was a year ago.
Let me start with our business performance. We're now through 3 quarters of the year, and we continue to deliver solid financial results. For the quarter, product revenues grew by 11% year-over-year. AVONEX continued to do well this quarter, with revenues up 6% year-over-year. The continued rollout of the AVONEX PEN autoinjector device in the EU and Canada fueled additional patient and physician interest in AVONEX, one of the most trusted MS therapies in the world. TYSABRI was a key driver of our overall growth. Revenues were up 26% year-over-year, and TYSABRI is on a trajectory to reach over $1.5 billion in annualized end market sales. As a result, total revenues were $1.3 billion, up 11% year-over-year, and non-GAAP diluted EPS was up 19% at $1.61.
This was a good quarter for TYSABRI, which continues to be a main growth driver for us. First, key data were presented at ECTRIMS in Amsterdam last week that showed that patients who received treatment with TYSABRI early in the course of MS received more clinical benefit than those who delayed treatment with TYSABRI and were first treated with immunosuppressive therapies or switched between glatiramer acetate and the interferons.
Second, we made important progress on our JCV risk stratification efforts, as the JCV antibody assay became commercially available in the U.S., as well as the EU. There are now over 59,000 patients who have been tested for JCV antibody status, highlighting the tremendous interest in risk stratification. We believe that this interest means that many patients and physicians are aware of the substantial benefits that can be gained from TYSABRI, as well as the potential risk of PML, and are using the information to make appropriate treatment decisions. I'm particularly encouraged by the increasing number of patients who have been tested, who are not current TYSABRI patients, and I believe that bodes very well for the future of the drug.
Turning to the advancement of our late-stage pipeline, as you all know, details of the defined study for BG-12, our oral candidate for MS, were presented at ECTRIMS last week. And top line data for CONFIRM, the second registrational trial for BG-12, were announced Wednesday. Doug will provide more details. Let me just say that both DEFINE and CONFIRM displayed compelling efficacy and safety data for BG-12. We now have strong positive results for BG-12 and 2 robust pivotal clinical trials with more than 2,600 patients. We're now focused on filing BG-12 with both the FDA and EMA, which will occur in the first half of next year, with the intent of bringing this potentially major new therapy to patients with MS as soon as possible.
Additional news this quarter from our late-stage pipeline, including data presented at last week's ECTRIMS meeting for SELECT, the first of 2 registrational trials for daclizumab, which is being evaluated as once monthly or biweekly subcutaneous injection for relapsing-remitting MS. SELECT showed impressive clinical results for daclizumab and supports the continuation of the second registrational study, DECIDE.
We also continued to make progress in the enrollment of ADVANCE, our Phase III trial, evaluating once monthly subcutaneous PEGylated Interferon for relapsing-remitting MS. And we expect enrollment to be complete by the end of the year. All of these accomplishments highlight the emerging suite of products that will allow Biogen Idec to fully serve all of the segments of the MS market, well-established, well-chronicled injectables, the highest efficacy segment, as well as the growing oral segment.
Moving on to the rest of the pipeline, we completed enrollment for EMPOWER, the first global Phase III study of dexpramipexole, for treatment of ALS or Lou Gehrig's disease. This was the fastest enrolling trial in Biogen Idec's history, which is largely a reflection of a tremendous need for therapies for this devastating disease. We now expect this trial to read out towards the end of next year. Our hemophilia long-lasting Factor VIII and Factor IX programs continued to enroll well. And both of those trials also are on track for data readout in 2012.
Finally, we announced yesterday that we entered into a collaboration with Portola Pharmaceuticals to develop and commercialize an oral highly-selective Syk inhibitor. This program plays to our strength and experience in immunology and has the potential to provide therapies for a variety of autoimmune diseases. This deal is an example of executing on our strategy to fill in our early-stage pipeline with high-quality assets.
As we continue the transformation of the company, I'm pleased to announce this quarter the promotion of Tony Kingsley to run Global Commercial Operations starting next month. Tony's been a key member of the commercial team and has led the turnaround of AVONEX sales in the U.S. With his combination of strategic insight and operational expertise, I'm confident that he's the right person to lead our Global Commercial business and prepare for the potential launch of multiple products in the next several years.
As you know, Francesco Granata has led a successful transformation of our commercial group, as evidenced by the continuing excellent performance of AVONEX and TYSABRI. I want to take this opportunity to publicly thank Francesco for his contributions to the success of Biogen Idec and for his positive leadership in the organization. At the same time, I want to welcome Tony into his new role. We're all convinced that Tony will take the ball -- take the baton and continue to build an industry-leading commercial organization.
So with that, I'll turn the call now over to Francesco for a more detailed update on our commercial performance for the quarter.
Thank you, George. As we have mentioned over the last several quarters, we started our journey with very clear goals and milestones for substantial growth of the business. I am proud to say that we continue to be on track to meet or exceed those goals.
Starting with our MS franchise part of revenue, overall, we saw 11% growth year-over-year. AVONEX growth continued this quarter, and units worldwide increased 1%. And revenues grew 6% on a year-over-year basis. Looking region by region, in the U.S., where we had focus on strategy and execution, AVONEX units were around 164,000, relatively stable over the last number of quarters and in line with our expectations, while revenues grew 6%. The brand has performed quite well in light of a new oral entrant and the competition for share of voice in the physician office.
In the European Union and Canada, AVONEX remains the market leader. And units grew 6%, while revenues grew 2% on a year-over-year basis. The AVONEX spend has now launched in the U.K., Germany, Netherlands, Canada, Norway, Sweden and Denmark. The PEN has a new interest in the brand for existing patients, new patients and those switching from other brands. In the U.K., where the PEN was launched this quarter, the number of net new starts for AVONEX has more than tripled compared to the 6 months before the launch. And our U.K. affiliate has added more AVONEX patients in the last 3 months than it did for all of 2010. We are very pleased with the momentum the PEN is creating for AVONEX while meeting the needs of the patients.
For the markets outside of Europe and North America, our MS franchise revenues grew 26% year-over-year, growing at a faster rate than our overall business. AVONEX revenues grew 20%, driven in part by tender market shipment for Q2 that were realized this quarter. An additional highlight is Japan, where AVONEX has reached 37% market share year-to-date. Our global footprint and emerging market strategy has paid dividends, continuing to provide revenue upside, as well as opportunity for future growth.
Turning to TYSABRI, worldwide units are up 16% year-over-year, and net new patients are up 2,100 since last quarter. While we saw positive growth in net new patients in the U.S., quarter-over-quarter, we saw some slowing of the growth of net new patients in the European Union, due in part to some seasonality among a number of markets and the penetration of the assay. This was not unexpected, and the continued growth of JCV testing by patients not currently taking TYSABRI is very good news. While there will be some quarter-over-quarter variation in TYSABRI net new patients, the overall trend remained positive, and we believe risk stratification is helping patients and physician to make an informed choice about TYSABRI therapy.
In the U.S., TYSABRI units grew 15% year-over-year, and patients number grew 8%. This is the fourth consecutive quarter where we delivered unit growth for TYSABRI in the United States. The JCV assay became commercially available in the U.S. this quarter as a laboratory-developed test, and there are roughly 33,500 patients enrolled and certified, too, through the end of September. This is a trend toward more nonuser of TYSABRI being tested for JCV status. Patient discontinuation have stabilized, and there is strong positive momentum for new TOUCH forms.
In the European Union and Canada, TYSABRI units grew 17% year-over-year, and patients number grew 20%. The commercial JCV assay has now been assessed by approximately 1,200 physicians and almost 20,000 patients as for the end of September. While these are initial trends, our market research indicated that nearly 1/4 of the patients being tested are not TYSABRI users, and that's approximately 70% of JCV positive patients. And 98% of JC negative patients stay on treatment with TYSABRI after being tested, showing the tremendous opportunity for TYSABRI continued success and acceptance by the MS marketplace.
In the emerging markets and rest of the world, TYSABRI units grew 23%, and patients grew 30% year-over-year. Brazil launched TYSABRI during the quarter, and TYSABRI is now available in over 60 countries.
This quarter, we acquired the Dompé JV in Italy and Switzerland. We are grateful for the job that Dompé did in launching and establishing our products in these markets. Making Italy and Switzerland direct affiliates for Biogen Idec was important for the profitability of our future Europe product launches. Our European footprint is now direct distribution for all of the major European countries.
I am pleased to announce that Carlos Dourado joined Biogen Idec this quarter to run our emerging market group, an area of the business that will benefit from his specific skills and experience. Carlos spent 32 years in various management roles with Schering-Plough in Brazil, Middle East, Europe, the United States and Canada. Carlos will be instrumental as we prepare to enter new markets such as China, Asia Pacific and other important future markets that will help shape our broader global presence.
While it is still early days, the launch of FAMPYRA in Germany has gained positive momentum. FAMPYRA addresses a high unmet medical need and has been shown to improve walking in all types of MS, both relapsing and progressive. It can also be given concomitantly with currently available MS treatments. FAMPYRA also became available during the quarter in Australia and U.K., and we anticipate launch in Denmark shortly. Additional launch preparation is underway for the rest of Europe, and we expect additional countries rolling out in 2012. And reimbursement discussion are finalized.
As you know, I have decided to leave Biogen Idec for personal reasons. I am proud that I have been able to accomplish the mission discussed when I joined the company: deliver strong commercial performance while preparing for future launches. I will be pursuing some other opportunities, which in due time will be communicated. And I am pleased that Tony Kingsley will take on the role of the Head of Global Commercial Operations. Tony has been responsible for the tremendous turnaround in the U.S. business and brings many important skills to the table. He has experience in leading several new product launches, as well as leading complex organization. He has turned around the mode of the U.S. business from a defensive posture to an offensive winning spirit. I have enjoyed my time at Biogen Idec. It is a great company, and I have tremendous confidence in the team that will now move the business forward.
With that, I will turn the call over to Doug Williams, EVP of R&D.
Douglas Edward Williams
Thank you, Francesco. During Q3, we made important advances on several aspects of our R&D programs, which highlight our novel science and continue to position the company for substantial future growth.
As George mentioned, on Wednesday, we announced positive top line results from CONFIRM, the second Phase III study of BG-12 in relapsing MS. We have now successfully completed DEFINE and CONFIRM, 2 randomized, blinded, well-controlled Phase III studies in 2,600 patients with relapsing-remitting MS, with very comparable, very positive outcomes. While there's still ongoing analysis being done with the CONFIRM study results, we're now aggressively working on regulatory submissions for BG-12 to file with the FDA and EMA in the first half of next year.
Very briefly, the CONFIRM study was a 2-year, multicenter, double-blind, placebo-controlled, dose-comparison study in over 1,400 relapsing-remitting MS patients, evaluating 2 doses of BG-12 in comparison to placebo for the reduction in annualized relapse rate or ARR at 2 years. The glatiramer acetate reference comparator arm was also evaluated versus placebo. Both the BID and TID doses of BG-12 met the study's primary and secondary relapse and MRI endpoints. With respect to reduction of ARR, the primary endpoint of the study, we saw 44% and 51% reduction for BID and TID doses of BG-12, respectively, and a 29% reduction for glatiramer acetate reference arm versus placebo. Data from CONFIRM also showed a favorable safety and tolerability profile, consistent with what was seen in DEFINE. Further detailed information from CONFIRM will be presented at an upcoming medical meeting.
Last week, we also shared comprehensive data from DEFINE, the first registrational study of BG-12, at the ECTRIMS meeting in Amsterdam. Both doses of BG-12 demonstrated significant clinical effects compared to placebo in the proportion of patients relapsing at 2 years, annualized relapse rate, multiple MRI measures and disability progression. Incidence of infections and severe infections were similar across all treatment arms, and no opportunistic infections were observed in the BG-12 treatment arms. While the incidence of flushing and gastrointestinal symptoms was higher with BG-12, these events were primarily mild to moderate and decreased substantially after the first month of treatment. We're very impressed with the robustness of the positive BG-12 data from both DEFINE and CONFIRM studies, and plan to file with the FDA and EMA in the first half of 2012. The data shows that BG-12 has a very favorable benefit-risk profile, and we believe that if approved, it will provide an important treatment option for patients with relapsing-remitting MS.
Turning to TYSABRI, 28 posters and presentations were presented at last week's ECTRIMS meeting in Amsterdam, highlighting the high standard of efficacy that TYSABRI has set in the MS market. Data from AFFIRM, a long-term outcome study, showed ARR and EDSS benefits seen with earlier treatment of TYSABRI over delayed treatment. Data was also presented from the TYSABRI observational study known as TOP. This study assessed long-term outcomes in almost 3,500 patients, and showed that mean ARRs in TYSABRI-treated patients were lowest in those that were treatment naïve at baseline and highest in patients who were previously treated with immunosuppressive agent or switched from another disease-modifying therapy, further supporting the benefits of early treatment with TYSABRI.
Last week, we and our partner, Elan, announced that the FDA notified us of a 3-month extension to the PDUFA date for the TYSABRI sBLA, for updating the prescribing information for TYSABRI to include anti-JC virus antibody status to further help stratify the risk of PML. The FDA has indicated that this extension is needed to allow time for review of the changes being incorporated into the risk evaluation and mitigation strategies, also known as REMS, to be consistent with the anticipated prescribing information. We and Elan are working with the agency to facilitate a timely review of the REMS changes and the sBLA.
And finally, for TYSABRI, we initiated patient enrollment in ASCEND, the Phase III trial of TYSABRI in secondary-progressive MS. This trial is expected to enroll 860 patients, and we'll investigate whether TYSABRI treatment slows the accumulation of disability not related to relapses and subjects with SPMS.
Turning now to other important aspects of our MS pipeline, in a late breaker presentation at ECTRIMS, we and our partner, Abbott Labs, announced additional data from SELECT, our first registrational study of daclizumab in relapsing-remitting MS. SELECT showed significant reduction in annualized relapse rate at 1 year and met key secondary endpoints. The overall incidence of adverse events and treatment discontinuations were similar in all study arms. Serious infections, serious cutaneous events and liver function test abnormalities greater than 5x the upper limit of normal occurred more frequently in the DAC-treated patients. We placed additional monitoring and management measures in the ongoing clinical programs for the cutaneous and LFT events. These data further support investigation of DAC in the ongoing DECIDE study, which is a randomized, blinded study of 1,500 patients with a primary endpoint of ARR at 2 years.
I'm pleased to say that we have received a positive decision from the European Commission for the AVONEX titration kit. The titration kit is designed to help mitigate flu-like symptoms at the start of therapy, making for better initial experience with AVONEX, one of the most trusted MS therapies available.
Lastly, enrollment for ADVANCE, our Phase III trial of PEGylated Interferon for MS, is on track to be completed by year-end. The trial is being conducted under a Special Protocol Assessment with the FDA. With an annualized relapse rate at 1 year as its primary endpoint, we anticipate top line data to be available in early 2013.
From AVONEX, with its 15 years of safety and efficacy experience, to TYSABRI, which sets the standard for high efficacy, and our anticipated introductions of BG-12 and daclizumab, we hope to offer MS patients a wide range of treatment options. Our portfolio of MS drugs is unrivaled in the industry and speaks to our commitment to the individual needs of different segments of the MS population.
Turning to the rest of the neurology pipeline, patient enrollment in EMPOWER, the first global Phase III study of dexpramipexole for treatment of ALS or Lou Gehrig's disease, has been completed well ahead of schedule. This highlights the high unmet need for new and effective therapies for ALS. Recall that we've agreed with the FDA on a Special Protocol Assessment for the design of this study. We anticipate top line data readout in the second half of 2012. We expect to initiate the second Phase III study of dex in the first half of 2012. Dex is a novel oral compound that potentially has neuroprotective properties based on experimental and preclinical studies and may slow the loss of motor neuron function, which is the hallmark of this devastating disease.
Moving on to our hemophilia programs, we continue to expect to complete the bulk of patient enrollment in both B-LONG and A-LONG studies in 2011, but there may be some carryover into the first half of next year. Recall that in the B-LONG study, there's a surgical arm which may take enrollment into next year. Data readout for both trials, however, remains on track for the second half of 2012.
Along with substantial progress on our late-stage clinical programs, we've also taken steps to bolster our earlier-stage development pipeline. We announced yesterday an exclusive, worldwide collaboration with Portola Pharmaceuticals to develop and commercialize what we believe will be a potent, oral, highly-selective Syk inhibitor. Inhibition of Syk has the potential to provide effective, well-tolerated therapies for a variety of autoimmune diseases, including lupus, rheumatoid arthritis and atopic diseases. We're encouraged by the preclinical and Phase I clinical data to date and see an opportunity to develop a best-in-class, highly-selective, once-daily oral treatment for a broad range of autoimmune diseases. We expect to begin Phase IIa testing of the lead compound next year in RA. This program plays to our strengths and experience in immunology and strengthens our Phase I, II pipeline.
I'm extremely pleased with the progress that the R&D organization has attained this quarter for our pipeline, which is one of the most enviable in the industry. I look forward to providing you with further updates on our progress in the coming quarters.
With that, I'll now pass the call to Paul Clancy, our Executive Vice President of Finance and Chief Financial Officer.
Paul J. Clancy
Thanks, Doug. I'll begin with our GAAP financials provided in Tables 1 and 2. Table 3 includes a reconciliation of GAAP to non-GAAP results. The difference between our GAAP and non-GAAP results for the third quarter include $49 million related to the amortization of acquired intangibles, $3 million for contingent consideration, $2 million for restructuring and $5 million in stock comp expense. This is partially offset by the tax impact on these items. Our GAAP diluted earnings per share was $1.43 in the third quarter, an increase of 36% over prior year.
Now I'll move on to the non-GAAP and P&L, which we believe better represents the ongoing economics of the business and reflects how we manage the business internally. Non-GAAP diluted earnings per share was $1.61 for Q3, a 19% increase versus prior year.
Moving to revenue. Total revenue for the third quarter was $1.3 billion, an increase of 11% over prior year. In the U.S., where AVONEX grew 6% to $411 million, inventory in the channel ended at just under 2.2 weeks, a slight decrease from last quarter, while shipping days remained consistent.
Internationally, AVONEX product revenue was $271 million, also an increase of 6% compared to prior year. The impact of foreign exchange strengthened AVONEX revenue by $22 million. However, this was offset by a $9 million hedge loss in the quarter as compared to a $17 million hedge gain in prior year.
Now moving on to TYSABRI. TYSABRI worldwide end market sales were $393 million in third quarter, up 28% versus last year, essentially flat versus the second quarter. Biogen Idec recorded TYSABRI product revenue of $277 million. In the U.S., TYSABRI product revenue to Biogen Idec grew 41% to $85 million, driven by unit and price growth. Q3 international TYSABRI product revenue was $192 million, a 20% increase. The impact of foreign exchange added $16 million to TYSABRI revenue versus prior year, which was offset by a $2 million hedge loss compared to a $4 million hedge gain in prior year.
Now I'll move to RITUXAN collaboration revenues. U.S. RITUXAN sales were $733 million in the third quarter, up 9% versus prior year, driven by increased penetration in the maintenance setting in non-Hodgkin's lymphoma and continued uptake in CLL. Our profit share from that business was $234 million. Royalties and profit share and sales of Rituximab outside the U.S. in Q3 were $32 million, down 17% due to royalty expirations. And we were reimbursed $1 million for selling and development costs incurred related to RITUXAN in Q3. The result was $266 million of revenue from unconsolidated joint business in Q3, an increase of 3% over prior year.
Internationally, FAMPYRA revenue were $3 million, as we began commercializing in Germany. Royalties were $52 million for the third quarter, an increase of 43% from prior year. The increase was due to hitting a new royalty tier in our partnership on ANGIOMAX. This new tier is applied to all year-to-date revenue in our accounting model. We achieved this one quarter prior to expectations, resulting in a potentially lower, more normalized royalty revenue in Q4. Additionally, we recorded $16 million of corporate partner revenue, driven by third-party manufacturing contracts with a strategic partner.
Now turning to the expense lines on the non-GAAP P&L. Q3 cost of goods sold were $124 million, representing 9% of revenues. The increase was due to a number of factors, including the third-party manufacturing, increased JCV assay test in Europe and increased costs for the AVONEX PEN, all important revenue-driving investments. Q3 R&D expense was $300 million or 23% of revenues. R&D expense was driven by the accrual on the dexpramipexole trial and the continued progression of the late-stage programs.
Q3 SG&A expense was $258 million or 20% of revenues, an increase of 7% over same period last year. Foreign exchange impacted SG&A by $12 million, and increased spend supporting new product launches drove the increase. This was offset by changes in our sales and marketing of RITUXAN.
Continuing down the P&L, our collaboration profit sharing line totaled $81 million for the quarter. Other income and expense was a loss of $8 million, and our Q3 non-GAAP tax rate was 26.4%, as we benefited from a higher level of orphan drug research credit.
In the third quarter, our weighted average diluted shares were $245 million. We ended the quarter with approximately $2.9 billion in cash and marketable securities, split approximately 65%-35% between the U.S. and outside the U.S. This brings us to our non-GAAP diluted earnings per share, which again were $1.61 in the third quarter, a 19% increase over prior year.
Let me provide a little bit financial detail on a few recent events. As Francesco noted, in September we completed the acquisition of our 50% interest in our joint ventures in Italy and Switzerland. The upfront purchase price was $153 million, which represents the settlement of equity reserves to our former partner and for future cash flow. Additionally, we're obligated to payments of $43 million upon the achievement of certain regulatory and commercial milestones. We also entered into an agreement whereby Dompé agreed to purchase 100% of the outstanding receivables in Italy. Prior to the transaction, the entities were fully consolidated into our income statement, yet 50% of the profits from the sales affiliates have been reported as a noncontrolling interest. Going forward, there will be no allocation to noncontrolling interest, and as a result, 100% of the operations will be reflected on our financial statement.
Moving to Portola. Under the collaboration agreement with Portola Pharmaceuticals, we will provide an upfront payment of $36 million in cash and $9 million in equity. These will be reflected in our financial statements in the fourth quarter.
Now moving onto our full-year guidance. We now expect full-year revenue growth of mid-single digits. We continue to expect COGS to be between 9% and 10% of sales, including the impact of AVONEX PEN, the JC virus assay investment and the increased cost of goods sold from contract manufacturing activity. R&D is expected to be at the higher end of 22% to 24% of sales, which now includes the $36 million payment in Q4 associated with our announcement with Portola Pharmaceuticals.
SG&A expense outlook is unchanged at the higher end of the range of 20% to 21% of revenue, driven partially by foreign exchange, launch cost for FAMPYRA and investment in BG-12. Our tax rate outlook for the full year is unchanged at 26% to 28% of PBT. As a result, we anticipate GAAP and non-GAAP EPS results above $4.91 and $5.70, respectively. Importantly, we've maintained our non-GAAP EPS guidance while covering the RITUXAN arbitration charge from Q2, second half launch investments and the business development activity just recently announced with Portola.
So a very strong financial outlook for 2011, driving double-digit earnings per share growth. Now I'll hand the call over to George for his closing comments.
George A. Scangos
Okay. Thanks, Paul. So to quickly sum up the quarter, we're very pleased with the solid performance of both AVONEX and TYSABRI, and with the strong overall financial results. At the same time, we made excellent progress on the pipeline. We have numerous programs in late-stage that have the potential to bring meaningful products to patients. Some of these will make it to the market and we're therefore posed -- poised for considerable growth over the next 5 years. We've continued the transformation of the company, adding to our early-stage pipeline with the recent Portola transaction, as well as the promotion of Tony Kingsley to EVP of Commercial Operations.
We've made solid progress on the goals we set out for ourselves at the beginning of the year and continue our positive momentum, clarity of mission and reinvigorated organization. Although we've accomplished a lot so far, we have a long way to go. We have to be and we will be focused on execution to make sure that we do our best for investors, ourselves and our patients, and effectively and efficiently move our late-stage pipeline through the clinic and registration and onto the market.
Finally, I want to thank the many employees at Biogen Idec who worked long and hard to help us achieve our goals. Without their dedication and passion, the achievements of the year-to-date wouldn't have been possible.
So with that, we'll close our remarks and open up the call for questions.
Thanks, George. Melissa, we're ready to open up the call for Q&A. [Operator Instructions] Melissa, we're ready for the first question.
And your first question comes from the line of Matt Roden from UBS.
Matthew Roden - UBS Investment Bank, Research Division
So I'm going to ask a question that you've probably gotten several times in one form or another. But now that CONFIRM is out, you might be in a better position to address it. And that is how Biogen will organize and prioritize its commercial detail. Once the 3 products are out in MS, that is AVONEX, TYSABRI and BG-12, all of these products have very nice but different commercial profiles. So it would be great to hear your thoughts on how you would position this new market and what potential impact it could have on margin and cash flow.
George A. Scangos
Sure. Nice problem to have, isn't it? Yes. Look, I think it's important to remember, MS is not a homogeneous disease. Different patients -- some patients progress more than others, some patients more concerned with safety than others, some really focused on efficacy, some don't like needles. And so it's really a heterogenous patient population. And the neurologists who treat them have different views as well, some more focused on safety, some more focused on efficacy. And so we now have products that play in all the major segments -- or we will, assuming BG-12 gets onto the market. So AVONEX is a great product. It's been on the market 15 years. Now it's no side effects, it's safe, it's effective. And for a lot of patients, AVONEX will be a very good choice for them for -- we have the PEGylated AVONEX -- PEGylated Interferon coming, which if successful, could make that dosing much more convenient to patients and increase interest there. TYSABRI is amazingly efficacious product. And for patients who are really concerned about efficacy, who have more aggressive form of the disease, who really want to get in charge of their disease, TYSABRI is a great product. And we have the recent data now showing that earlier treatment with TYSABRI has -- leads to better long-term outcomes. So I think for an increasing number of patients, TYSABRI will be a very good choice. And BG-12, you saw the data. It's a remarkable compound. So there will be a large segment of the patient population, I believe, that will want on oral compound. Obviously, BG-12 is not the only oral compound that they'll have to choose from, but we believe BG-12 stacks up very well and will be a very strong competitor in this segment of the market for patients who want an oral therapy. So I think by having a variety of products like that for patients with different needs, different concerns, we can really maximize the total market share that we have.
And then we have staffed very appropriately in advance, all the global strategic functions and also the local markets to be prepared to conduct appropriate positioning and messaging study. So we are ready to move to the next step also by having the right staff in place, globally and locally.
Your next question comes from the line of Gene Mack from Mizuho Securities.
Gene Mack - Mizuho Securities USA Inc., Research Division
Wondering if you can talk a little bit about the clinical implant for dexpramipexole. It looks as though you've gotten FDA to agree to a modification of the ALSFR Scale. I'm just wondering if you can maybe -- maybe for Doug, if you could talk us through what that endpoint looks like as opposed to the ALSFRS in its standard form.
This is Al Sandrock. The -- it's actually a joint rank score where you evaluate both the survival aspects, so the time to death, and you combine that with the ALSFRS. So it's really both a functional as well as survival outcome. And basically we call it a rank score because you rank patients. You first start by ranking patients based on when they die. And after you finish ranking patients based on that, then you rank them based on how fast they decline on the ALSFRS. Of course, we're looking for differences between dexpramipexole and placebo.
Your next question comes from the line of Ravi Mehrotra from Crédit Suisse.
Ravi Mehrotra - Crédit Suisse AG, Research Division
Various sources and checks that we get give us an impression that there's a very significant diagnosed but untreated multiple sclerosis population, a warehouse population, if you will. Given your expertise in the market, can you give us your view on this population? Specifically, how big do you think it is? What sort of patients are within it? And ultimately, do you think it's a pool where BG-12 can make an impact?
Paul J. Clancy
Yes, this is Paul. I think the insight that we have is probably very similar to what your understanding is, is that "quarter population" in the marketplace or -- and that they're very dissatisfied for a range of reasons. So that kind of the current injectable market, the current injectable product offerings, many patients don't like injectables for obvious reasons. Many patients have tolerability issues with handling the flu-like symptoms, particularly in the early course of treatment. Our estimates have been that those are at least 100,000 patients, kind of on the sidelines, potentially more than that. I think what we're seeing in the launch period of Gilenya is bringing some of those into the marketplace. Clearly, you've seen from them that at least half or more of their patients are coming from that pool. I think it bodes extremely well for BG-12 and the potential to launch into that marketplace, especially as BG-12 safety profile has this opportunity to differentiate itself in the kind of oral -- emerging oral segment.
And the other point is that, Paul, is some of the emerging markets, Brazil, but not only Brazil, Russia and other markets, clearly has an underdiagnosed and undertreated MS population. And we are -- again, our strategy is to strengthen our position in those market to be ready to capitalize and also work with physicians and patients to increase the level of awareness about the BG. So we expect that also these markets will contribute to, in part, to the emergence -- to the new patients pool availability.
Your next question comes from the line of Mark Schoenebaum from ISI Group.
Mark J. Schoenebaum - ISI Group Inc., Research Division
I had a question actually for Paul or maybe it's George. I'm not totally sure. But $3 billion of cash, it's a lot of cash. $2 billion, if I heard you correctly, roughly, that's sitting in the U.S. The obvious question, what are you going to do with it? And maybe more specifically, how has the BG-12 data changed the way you're thinking about the use of that cash in terms of perhaps any criteria? And specifically, have you thought about buying -- trying to buy down some of the BG-12 contingent payments that you may owe eventually?
Paul J. Clancy
Okay. I think that -- hey, Mark, I think that was pretty good. It's 1 question that had 3 parts to it, as best as I can tell. Look, it is at a high point now. I think we have -- we're starting to approach a level that is higher than cash balance that we've had in any point in time. It's a -- and I think the company's robust cash flow generation outlook actually is good for -- certainly continues on and potentially accelerates. We've had a track record of trying to be extremely disciplined, and our focus has been really all about trying to use that cash to drive the greatest amount of shareholder value. Clearly, over the last kind of number of months, we continue to look at it and trying to understand it. Nothing to report at this point. We review strategic opportunities, I think, fundamentally as a management team, as a board. We believe shareholder value creation happens with bringing in assets, pre-proof of concept, bias. And I think that's what we've shown over a long period of time with the evolution of our late-stage programs now. Many of those were deals that were done in a number of years ago in a very efficient way. So we'll continue to look at it, nothing to report, per se. But we have our eye on trying to be very disciplined, very strategic about kind of deploying that cash, a good high-class problem to have. With respect to kind of your specific question, I think nothing -- those opportunities aren't lost on us in terms of, are there ways to deploy it -- deploy cash to buy down future obligations? It really becomes, does it make sense? And is it a bid-and-ask type of thing? It really is very deal-specific and specific to each individual opportunity. And we'll be equally disciplined on that front as well.
Your next question comes from the line of Michael Yee from RBC Capital Markets.
Michael J. Yee - RBC Capital Markets, LLC, Research Division
A question for Doug or Al. Have you looked at or can you comment on what work you've done, improving the tolerability of BG-12 at the start? There are a lot of European docs out there talking about the ability to use aspirin with FUMADERM. And I know you've run an early Phase I study in healthy volunteers. Can you maybe comment on what came out of that or what your experience has been around that?
So this is Al. We have run a small study to evaluate the effects of drugs like aspirin to mitigate tolerability of BG-12. And as you know, we're not quite ready to talk about the results at this time. But I can tell you that we are -- we will soon be talking about it. We have completed the study. So, Doug, I don't know if you want to add anything.
Douglas Edward Williams
No, I'd just point out that I think the conclusion from the study as well is that what we've seen are sort of mild to moderate issues that haven't really contributed to the discontinuation rate in a meaningful way. So that, plus the fact that these side effects tend to wane with further treatment, we don't see them as a real issue.
Your next question comes from the line of Eric Schmidt from Cowen and Company.
Eric Schmidt - Cowen and Company, LLC, Research Division
Another kind of BG-12 future question. I also noticed you have a new formulation in clinical trials. I was wondering what that's about, whether that speaks to tolerability or patent life or what have you. And maybe a second part to the question, what other indications are you thinking about starting up trials in with BG-12?
Yes, that's actually -- I'd characterize that as a life cycle management study to look at the ability to consolidate pills and to make it easier for patients. So instead of 2 pills, it would be 1 pill.
Eric Schmidt - Cowen and Company, LLC, Research Division
Oh, and other indications, still noodling on that, I think, as a team at this point. But certainly, with neuroprotection, based on the mechanism, I think you can conjure up a few other potential indications that might make some sense.
Your next question comes from the line of Robyn Karnauskas from Deutsche Bank.
Robyn Karnauskas - Deutsche Bank AG, Research Division
So I was just going to ask you a question about one of the things you mentioned on the call. You noted that about 70% of the JCV positive patients are staying on therapy, and that seems really impressive to me. Maybe you can comment on, do you expect -- how -- what do you think would be the long-term percentage of JCV positives that remain on TYSABRI? How should we think about that? And maybe in the EU, what might be some initial color on how the JCV assay is affecting new patients coming to drug and discontinuations?
As we outlined in the -- earlier, there are -- we have seen a few trends. One is the high-level of stability of patients who are virus-positive, and we expect this to continue, given the efficacy profile of the drug and given also the other risk factor which associated time and prior exposure to immunosuppressant. The other -- we have seen also an extended use of the JC virus on testing patients who are not on TYSABRI, which make us feel that there will be more patients who will be considered for TYSABRI use than before because of the JC virus assay. What we see in Europe is not very different from what we have seen in the United States. You should remember that Europe has a slightly higher use of immunosuppressant as a first-line therapy for MS than the United States. So it might be that the initial impact could be slightly different from the United States. But the key learnings that we have from the U.S. market has been shared with the European affiliates. So there is a more robust question in the asset management done by the reps whenever possible or by MSs. So we are really confident that the tool will become an important tool to expand the use of TYSABRI user and keep the right positive patients on the drug. I cannot comment on exact percentage. We are still investigating through market research. But, again, we're listing that TYSABRI will continue to be an important tool for patients and physician to treat MS.
Your next question comes from the line of Geoff Porges from Bernstein.
Geoffrey C. Porges - Sanford C. Bernstein & Co., LLC., Research Division
I thought I'd just follow-up on the JCV assay. Could you give us a sense of roughly what number of patients -- now you've sort of gone through the various trials, what number of patients are being tested on, say, a quarterly basis? And then the distribution of who's doing the test between you and Quest and any other commercial vendors. And lastly, as this is really related, we've heard reports of false negatives on the commercial assay. I wondered if you talk about that and whether you're seeing people sort of doing confirmatory testing or anything or if there's a higher false negative rate out there.
George A. Scangos
You take the scientific one first, okay?
Douglas Edward Williams
The false negative? Yes, I mean, we've not heard the reports that you've heard about false negative testing. Thus far, we've not had reports come to us that can be confirmed of a false negative. It's an assay that we transferred. It's basically the assay that we put together and validated. And so we have a lot of confidence in the way the assay is being run in the commercial setting, as well as in the experimental setting, when we run the assay in the stratified trials and then samples come back to us. So that's -- we have a lot of confidence in the assay in terms of how robust it is. Obviously, the regulatory bodies do as well. At least in Europe, we've got that now in the label as a stratification tool.
Paul J. Clancy
And then, Geoff, let me give a little bit of background on your kind of question of Quest versus the trial. And you went through the deck, so you probably have these stats, but maybe for everyone. To date, going back to spring of 2010, we now have had over 59,000 patients globally that have been tested for the JCV antibody status. The highest proportion of that is STRATIFY 2. That is just under 34,000 patients. To your specific question on Quest versus STRATIFY 2, which is kind of really -- kind of, I think, the nub of your detailed question, which is in the United States, those are the 2 options. Quest is really just about 30 days in. So there is a de minimis amount of Quest assays through the third quarter. The majority are still STRATIFY 2 in the third quarter. And obviously the difference is, in STRATIFY 2 it's a limited number of sites. It's a big number of sites, but a limited -- it's not all the centers across the United States, whereas Quest allows that to happen. That hasn't really penetrated yet. Obviously, we're awaiting the PDUFA deadline in the United States, the extended PDUFA deadline in order to really kind of get that thing going. We had -- our objective always was to try to synchronize the label with the commercial availability in the United States. We've got the commercial availability a little bit prior to the label. Unilabs is outside the United States. That is about 20,000 tests to date. Of that 20,000, there were about 10,000 test -- assay tests in the third quarter alone. So that uptake in Europe, per se, has been very, very, very strong. And I kind of think it probably had, as we have alluded and Elan alluded, a bit of an impact on discontinuations. But it still is quite strong kind of patient growth, even in light of that in Europe. And as Francesco had noted, what we're now seeing is a migration to both naïves of non-TYSABRI patients being considered in Europe. Hopefully, that provides a little bit of color.
Your next question comes from the line of Werber from Citi.
Yaron Werber - Citigroup Inc, Research Division
So maybe a question -- I'm not sure if Tony is there or George. What do you think -- how do you think the strategy may change? Or how may you guys kind of look at the way you're commercializing the drugs, now that Francesco is moving onwards? And then secondly, the BG-12 data obviously looks great, right? And tolerability is very good. Are you considering at all doing maybe a head-to-head switching study, maybe against one of the other ABCRs and patients who are currently stable as a way to switch them over? I mean, the first-line market obviously is not huge, but docs are going to BG-12 probably anyway for switching. But the question is, do you want to even show them data?
George A. Scangos
Yes, look, I don't think we anticipate any meaningful changes in how we've been marketing our drugs at all. Francesco and Tony have been working closely together now for almost 2 years. They've both been part of the success that we've had so far. So I think we'll go on in much the same way as we have in the past. If it ain't broke, don't fix it, right? It's our strategy. Our execution has been working well so far, and we'll keep it up.
Yes, again, thank you, George. I think strategy remains the same. Strategy goes from the right positioning of the drugs, first of all, the right pricing for the drugs, the right messaging for the drug and then the appropriate training and field force allocation, which is exactly what we have been doing to continue to co-position TYSABRI and AVONEX. Now we have another nice problem to have. And we are pretty sure that by continuing to fine-tune the strategy around those lines, again, right message; right positioning; right messaging; right field force training at the location; and clearly, rightsizing of the field force, we'll continue to be successful in this market.
Your next question comes from the line of Rachel McMinn from Bank of America Merrill Lynch.
Rachel L. McMinn - BofA Merrill Lynch, Research Division
Yes, 2-part but unrelated. Just, Paul, I wanted to get your sense on gross margins, whether we should expect them to worsen a little bit before they get better, just all the factors that they increased cost with testing, but perhaps benefiting longer-term from the TYSABRI manufacturing switch. But a clinical question as well on JC-virus-positive patients. It seems like people want to stay away from them because they're worried about, if they test positive and they've already been on TYSABRI, they're afraid of kind of seeing PML with their drug, like Novartis, for example. I'm just wondering if you're contemplating doing any specific testing in those patients who've been on TYSABRI and maybe switching them to BG-12.
George A. Scangos
Yes, I have heard some concern from colleagues about putting people who are JCV antibody positive to other drugs that are immunomodulatory. That concern is, I think, natural. So -- but other than that, in terms of doing studies on that, we're not there.
Paul J. Clancy
And then, Rachel, for the gross margins, I think -- broadly speaking, I think you have it right, is that there is probably unfavorable pressure in the short term on gross margins, driven by exactly what it was in Q3. And the PEN put a little bit of pressure on that. The assay, we're now funding that -- we're essentially funding that in Europe. We will be funding that in the United States, and that will impact the cost of goods sold line. And then this impact that we saw that helped out a little bit on revenue in terms of contract manufacturing comes with very high cost of goods sold. So -- but all of those, to some extent, will alleviate over the longer term, right? We hope to get the assay, particularly in the United States at some point in time, reimbursed through normal channels. The contract manufacturing, while it comes with high cost of goods sold in the short term, the longer-term impact of that is creating a far more efficient biologics manufacturing platform, a far more efficient in that has benefits through all of our products. And that shows up essentially around -- very correlated with the months of inventory that we have in the business, which is plentiful because of the nature of this business. And then we also do see improved margins down the road again, with kind of the opening up of the Denmark plants, and specifically third-party royalties avoidance on the TYSABRI products. So I think it all bodes well, but it just is a little bit longer term. In the short term, the assay, the PEN are very, very good investments. I view them as very, very good investments that are showing up and helping out the buoyancy of AVONEX and certainly risk stratification on TYSABRI penetration.
Your last question comes from the line of Sapna Srivastava from Goldman Sachs.
Sapna Srivastava - Goldman Sachs Group Inc., Research Division
I just wanted some more color on the current switching rate in the existing MS market. And also, just how do you think, when BG-12 enter the market, it can change it? And what have we learned from Gilenya's experience so far? And clearly, with BG-12 supply being so different, how do you think that can effect a change?
I think that -- yes, a good question. I think, that it was, in part, answered by the previous questions. And thus, we have seen that what Gilenya has done is that it brought more patients back to the MS panel. And we have also seen that there is probably an increase of switches. The switches will occur a little bit earlier, switches for both efficacy and tolerability. And so we expect that this trend, given that there is a high expectation for oral drug, will continue to be in the market, and will probably expand a little bit. And on top of that, as I said before, there will be more patients coming from emerging markets, not all of them, because of the prevalence of the disease. But emerging market will have better diagnosis and will have also better healthcare system in the future. So we expect that there will be a continuous growth of the MS market because of this combined factoring. Particular, as you mentioned, for oral treatment, still noticing that there will be also some -- these remain for the high-efficacy end of that. And still, market will remain for also drugs that are well-established on the market because of their long-term established efficacy and safety profile. So we think we are in a very good market, and we are competing in this market with the right answer for all the patients and physicians.
That was our last question. Thank you for your participation in today's call. You may now disconnect.
Copyright policy: All transcripts on this site are the copyright of Seeking Alpha. However, we view them as an important resource for bloggers and journalists, and are excited to contribute to the democratization of financial information on the Internet. (Until now investors have had to pay thousands of dollars in subscription fees for transcripts.) So our reproduction policy is as follows: You may quote up to 400 words of any transcript on the condition that you attribute the transcript to Seeking Alpha and either link to the original transcript or to www.SeekingAlpha.com. All other use is prohibited.
THE INFORMATION CONTAINED HERE IS A TEXTUAL REPRESENTATION OF THE APPLICABLE COMPANY'S CONFERENCE CALL, CONFERENCE PRESENTATION OR OTHER AUDIO PRESENTATION, AND WHILE EFFORTS ARE MADE TO PROVIDE AN ACCURATE TRANSCRIPTION, THERE MAY BE MATERIAL ERRORS, OMISSIONS, OR INACCURACIES IN THE REPORTING OF THE SUBSTANCE OF THE AUDIO PRESENTATIONS. IN NO WAY DOES SEEKING ALPHA ASSUME ANY RESPONSIBILITY FOR ANY INVESTMENT OR OTHER DECISIONS MADE BASED UPON THE INFORMATION PROVIDED ON THIS WEB SITE OR IN ANY TRANSCRIPT. USERS ARE ADVISED TO REVIEW THE APPLICABLE COMPANY'S AUDIO PRESENTATION ITSELF AND THE APPLICABLE COMPANY'S SEC FILINGS BEFORE MAKING ANY INVESTMENT OR OTHER DECISIONS.
If you have any additional questions about our online transcripts, please contact us at: email@example.com. Thank you!