Good morning. My name is Dan, and I will be your conference operator today. At this time, I'd like to welcome everyone to the Biogen First Quarter 2018 Financial Results and Business Update All lines have been placed on mute questions. Thank you. I would now like to turn the conference over to Mr.
Matt Calistri, Vice President, Investor Relations. You may begin your conference.
Thanks, Dan. Thank you, and welcome to Biogen's first quarter 2018 earnings conference call. Before we begin, I encourage everyone to go to the Investors section of bajan.com to find the press release and related financial tables, including a reconciliation of the GAAP to non GAAP financial measures that we'll discuss today. Our GAAP financials are provided in Tables 12. Table 3 includes a reconciliation of our GAAP to non GAAP financial results.
We believe non GAAP financial results better represent the ongoing economics of our business and reflect how we manage the business internally. We have also posted slides on our website at all of the discussions related to this call. I would like to point out that we will be making forward looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail.
On today's call, I'm joined by our Chief Executive Officer, Michelle Vanazzos Doctor. Michael Ehlers, EVP of Research And Development and our CFO, Jeff Capello. Before I conclude, I would also like to note that, starting with the Q2 2018 earnings call, we will post press releases related to future earnings calls materials and investor events on the Investors section of Biogen's website, www.biogen.com, and issue a statement on Twitter when they become available. We will do this instead of publishing press releases related to future earnings calls, earnings releases, and investor events via Newswire Services. Our Twitter handle is at Biogen.
Now, I
will turn the call over to Michelle.
Thank you, Matt. Good morning, everyone, and thank you for joining us. First, let me begin with some financial highlights. Biogen started 2018 with 1st quarter revenues of $3,100,000,000. On an apples to apples basis, excluding hemophilia, revenues grew 15% versus the same period a year ago, including hemophilia revenue grew 11%.
1st quarter 2018 GAAP earnings were $5.54 a share a 60% increase versus the same period a year ago. And non GAAP EPS was $6.05, a 16% increase versus the same period a year ago. We are pleased with our double digit top line and bottom line growth. Our new management team is taking meaningful action to secure our long term leadership in neuroscience including strong execution on our core business a renewed focus on business development, ramping up our internal R and D productivity and implementing an enhanced operating model designed for the future. Now let me review the solid progress we made in the first quarter.
First, our MS core business, including OCREVUS royalties, delivered revenues of $2,100,000,000, Globally, our core franchise remain resilient as reflected by continued growth in number of MS patients and new starts on Biogen Therapy. In the U. S, the good news is that we saw improving demand of our MS products and our discontinuations remain relatively stable. However, we saw the usual seasonality and a larger than expected inventory drawdown. Outside of the U.
S, our volumes grew in our priority markets and we continued our strong progress in the emerging markets. Overall, this performance is in line with our expectations but there are some puts and takes that Jeff will discuss in more details. We remain absolutely committed to our MS business and we are furthering our life cycle management initiatives by advancing the development of BIIB098 with our partner Alkermes, with a plan to file for regulatory approval in the US later this year by initiating efficacy studies and further data generation for the extended interval dosing for Pysabri as we build on the data presented at Actrims. By beginning, the development of PLEGRITY I'm as another potential convenient and efficacious options to bolster our market leading interference franchise and by continuing to pursue Opicinumab as a potential remedination therapy. 2nd, SPINRAZA, the only approved medicine for SMA with global revenues of $364,000,000.
The number of patients on SPINRAZA grew to approximately 4100, an increase of over 25% from last quarter and Jeff will be providing more details on this performance. Overall, worldwide SPINRAZA performance was slightly ahead of our expectations as lower than expected U. S. Uptake in the adult segment was offset by stronger than anticipated performance ex U S. We continue to focus our efforts and resources on the more than 5000 untreated pediatric and other patients in the US and even greater number of untreated patients outside of the US that we believe could benefit from SPINRAZA.
In the U S, we believe we have those more than half of infants and close to half of pediatric patients where we believe much more opportunity remains. At the end of the first quarter, approximately, 25% of patients treated in the U. S. Were adults, 18 years or older, an increase from 20% last quarter. We believe this is very encouraging trend, particularly now that we have expanded our sales team and can dedicate more resources and efforts to the large pediatric and adult segment of the SMA population.
Outside of the U S, we continue to expand and we are now treating over 1800 patients. We believe the rapid sequential reimbursement approvals and future launches are critical to achieve our long term goals. I am especially proud of our team's success, securing reimbursement in an additional 7 markets, meaning we now have reimbursement in 24 countries, of which 17 achieved formal reimbursement and 7 have individual case by case reimbursement. We now have formal reimbursement for over 400,000,000 covered lives ex U. S.
And we expect to receive formal reimbursement in at least 7 more countries by the end of 2018. In summary, beyond the seasonality and channel dynamics, our core MS business continued to be resilient and we continue to see significant future growth potential for Spinraza. 3rd, we expanded further our neuroscience pipeline and capabilities. We added BIIB-one hundred and four, a Phase 2 asset for neuropsychiatry and we entered into an exclusive 10 years collaboration agreement with Ionis that we believe will differentiate Biogen as the leader in developing ASO therapies for neurological diseases. We believe our exclusive access to IONE's market leading ASO platform for the CNS is a remarkable competitive advantage that has the potential to generate Our cash generation remains very strong and continues to provide us with significant optionality and flexibility in terms of capital location, importantly.
And as we have demonstrated in the past, we are committed to maximizing returns over the long term for our shareholders, something that demands a thoughtful approach towards all our investment. As you can see, our newly aligned management team is implementing our updated strategy and delivering noticeable results. We are working to create a leaner and simpler operating model, and we are strategically allocating capital as we invest to develop and expand our neuroscience portfolio again with the objective of maximizing shareholder returns. I will now turn the call over
Thank you, Michelle, and good morning, everyone. Last July, we communicated our vision for securing definitive leadership in neuroscience. This past quarter, we have executed against our goal to meaningfully enhance our pipeline by adding or advancing 5 clinical stage programs. Improving our research productivity and bolstering our portfolio of preclinical assets. Core and emerging growth areas.
Starting with MS And Neuro Immunology. This week, we are presenting data at the 70th annual meeting of the American Academy of Neurology, or AAN, which is also presented at Actrims regarding real world use of Tysabri and the potential impact of extended interval dosing on the risk of PML. A post hoc analysis of data from the touch database supported an approximately 90% reduction in the risk of PML when taking Tysabri using extended interval dosing dosing. If this additional research supports a high level of efficacy with a lower risk of PML, we believe it would represent a significant advancement in the treatment of MS. This builds on our broader risk stratification efforts for Tysabra including the use of JCB index values.
Earlier this month, the FDA approved and updated label, highlighting the association between index values and the risk of P and L. Further, Alkermes will be presenting data at AAN from the Evolve MS-one study, which is a phase 3 open label, long term study of our partnered monometh Fumarate prodrug BIIB098 in patients with relapsing remitting MS with 528 patients enrolled to date. In a 1 year interim analysis of exploratory efficacy endpoints, the annualized relapse rate in patients treated with BIIB098 was 0.16 and there was a significant reduction in number of gadolinium positive lesions from baseline to year 1. These preliminary results for annualized relapse rate and MRI parameters support BIIB098 as a potential oral treatment option for patients with relapsing remitting MS. Alkermes is planning to file safety profile in many years of patient experience, we believe that interferon therapies will continue to play in a important role for MS patients.
To that end, and as Michel mentioned, we are pleased to announce plans to develop an intramuscular formulation of Plegrty with the goal of reducing injection site reactions. Ultimately, with the aim of delivering a therapy with safety and tolerability comparable to Avenix, but with the efficacy and dosing convenience of PLEGRITY. Finally, we continue to advance the Phase 2b study of opicinumab as a potentially transformative therapy for many MS patients by promoting remyelination with the goal of aspire to create new options for MS patients and aim to maintain our long term leadership position in MS. We believe our patients across the full spectrum of the disease, and we are committed to pursuing new advancements to address the remaining unmet needs of MS patients. I'll now turn to our progress in Alzheimer's disease in dementia.
We continue to advance our leading Alzheimer's portfolio with multiple assets across complementary modalities and pathways, including the industry's most advanced program targeting beta amyloid. We presented a new analysis Aducanumab demonstrated up to 71% reduction in amyloid plaque on the scintilloid scale, a method used to standardize pet results. This is the largest degree of plaque reduction ever observed in the field. We believe each new analysis of the phase 1b data reinforces aducanumab position as the most advanced potential disease modifying therapy for Alzheimer's disease across the industry. Also targeting beta amyloid BAN2401, the A beta antibody currently being developed by our collaboration partner ASI, is continuing to the final 18 month readout in the third quarter of this year.
And the base inhibitor elenbecestat continues to recruit in phase 3 studies also being conducted by our collaboration partner Eisai. Beyond A beta, we believe that tau plays an important and complimentary role in Alzheimer's disease pathology, and we are advancing a suite of TAO assets. We have begun screening patients in the phase 2 Alzheimer's disease trial of BIIB092 the anti tau antibody we licensed from BMS last year, and we expect data from the phase 1 study of BIIB-seventy six, another anti tau antibody by the end of this year. Further, our 1st in class tau antisense oligonucleotide BIVADI is advancing in Phase I studies. Turning to neuromuscular disorders, we made significant progress in our strategic priority of spinal muscular atrophy.
In March, we presented important new data for SPINRAZA at the Muscular Dystrophy Association Clinical Conference. New interim Phase II results from NURTURE studying presymptomatic infants with SMA showed that all infants treated with SPINRAZA were alive, did not require permanent ventilation and showed improvement in motor function and motor milestone achievements compared to the decline normally seen over the course of the disease. All nurture participants achieved the age expected WHO motor milestone of sitting without support. We also presented a case series of 5 SPINRAZA treated patients with SMA Type 2 or 3 between the ages of 1719 upon their last visit, showing stable or improved motor function and improved quality of life. These data are important and support the clinical value of SPINRAZA for older patients who represent the majority of the current prevalence of the disease.
We aim to continue to extension study for patients who had transitioned from the Endeere study demonstrating long term benefits for infantile onset SMA in terms of both improved motor function and longer event free survival. And in collaboration with Columbia University, we are also presenting a case study of 14 later onset patients between the ages of 2 15 showing that with SPINRAZA treatment, they were able to walk longer distances while experiencing decreases in fatigue. In February, the end of study results from the SPINRAZA Phase III cherish study were published in the New England Journal of Medicine, another important acknowledgment of the unprecedented benefits that SPINRAZA provides to later onset patients. Biogen remains committed to advancing the standard of care in SMA beyond SPINRAZA. We continue to advance our gene therapy program in collaboration with the University of Pennsylvania with study initiation expected in the middle of the year, but we are not stopping there.
We believe that the future treatment landscape may involve combination or sequential therapy across different modalities. We have heard reports that 7 of the 15 patients in AveXis Phase 1 gene therapy study have subsequently gone on to SPINRAZA suggesting that clinical experience to date may support the utility of ASOS in combination with gene therapy. Sequential or additive benefits of gene therapy and ASOS could include additive effects on protein levels on a per cell basis, complementary distribution and transduction across the CNS and durability and stability of epizymal transgene expression. These are some of the reasons we are actively pursuing a strategy to evaluate Spinraz in combination with gene therapy. Put simply We do not believe that gene therapy will replace ASOS, but rather provide a complimentary modality.
Moving to our progress in movement disorders. At AAN, we are presenting Phase 1 data for BIIB-fifty four, our anti alpha synuclein antibody for Parkinson's disease, BIB-fifty four demonstrated favorable pharmacokinetics as well as a safety and tolerability profile, which support advancement into the ongoing phase 2 trial. At AAN, we are also presenting Phase 1 data for our anti tau antibody BIIB092 in progressive supranuclear palsy, which was well tolerated and demonstrated reductions in CSF retail levels of over 90%. We laid the foundation for our entry into neuropsychiatry this quarter with our agreement to acquire a phase 2b ready amperceptor potentiator now called BIV-one hundred and four from Pfizer. This transaction has now closed.
SYB-one hundred and four is a 1st in class molecule, initially targeting cognitive impairment associated with schizophrenia, or CIS, a devastating aspect of schizophrenia with no current treatment options. We believe fib-one hundred and four has compelling data from a number of distinct early clinical studies demonstrating functional circuit activation as measured by F MRI, treatment effects on relevant domains of cognition, and the potential for a favorable benefit risk profile. In particular, the multiple ascending dose study in stable subjects with schizophrenia demonstrated dose dependent effects on improvement from baseline to day 14 across multiple cognitive domains, including working memory, short term memory, verbal recall and reasoning. Importantly, we saw correlation as clinical efficacy with plasma exposure. We believe this molecule is differentiated from prior compounds in the class due to its high potency and favorable PKPD profile, which we believe allows for an improved therapeutic index.
We plan to initiate a Phase 2b trial in CIS by the end of the year in parallel to exploring additional studies across other indications supporting our core growth areas. Within acute neurology, we are excited about the potential for BIIB 93, our first class IV gluvancomyte therapeutic targeting BRAIN edema in large hemispheric infarcts. We plan to start our Phase III study in the middle of this year. We also recently initiated the phase 2 study of Natolizumab in drug resistant focal epilepsy and we dosed the 1st patient last month. Within neuropathic pain, we are advancing BIIB074 into Phase III for trigeminal neuralgia with start up activities outside the U.
S. In parallel to FDA engagement. II study of BIIB074 for painful lumbosacral radiculopathy with data expected towards the end of the year. And we've begun screening patients in a Phase II trial of BIIB07 for in small fiber neuropathy as we explore multiple potential indications. Given the high unmet medical needs of neuropathic pain patients, especially in light of the growing opioid epidemic, we are excited to expand our pain portfolio with the recent initiation of a phase 1 study for BIIB095.
Our second NaV1.7 inhibitor. Within ophthalmology, our partner AGTC recently completed enrollment in the phase 1two trial of its AAV based gene therapy program for X linked retinoskinesis or XLRS. Top line data are anticipated by Q4 with the final analysis at the 12 month time point. Last week, AGTZ also dosed the 1st patient in the Phase III study in Exelix retinitis pigmentosa, or XLRP. Underpinning all of our efforts across our core and emerging growth areas is investing in core capabilities platforms and modalities to enhance our translational machine in neuroscience.
To that end, last week we announced a new exclusive 10 year collaboration agreement with IONIS Pharmaceuticals to develop novel antisense oligonucleotide drug candidates for a range of neurological diseases. This partnership brings together the industry leader in ASO drug discovery with the industry leader in neuroscience drug development to create what we believe will be a powerful CNS genetic medicine engine. Based on our experience with SPINRAZA and other ASOS we have in development, We believe that intrathecal asos may address many genetic diseases and genetic targets of the central nervous system, including some pathways that were previously undruggable with small molecule monoclonal antibodies. Given their ability to directly intervene at the genetic origin of disease, we believe ASO approaches have a higher probability of success than traditional modalities with a more efficient development path and greater potential speed to patients. We believe this collaboration solidifies a key pillar of our R and D strategy to become the leader in neuroscience.
We aim to advance several SPINRAZA like drugs to patients CNS in particular. Now with an industry leading CNS ASO platform partnership secured, we further aim to build emerging synergistic modalities, including gene therapy to further augment Biogen's leadership in neurological diseases. We see high complementarity for ASO therapeutics in gene therapy, Intrathecal ASOS can be well tolerated, exquisitely selective, can up or down regulate gene expression, may be readily manufactured, may not be subject to immune surveillance and exert effects that may be reversed based on drug pharmacokinetics. We further believe that a powerhouse ASO platform will significantly augment our overall approach to genetic diseases and targets of the CNS. Please refer to our webcast from Friday, April 20, which is available on our website for more details on this new collaboration.
Overall, we had a remarkably productive quarter across our pipeline in both our core and emerging growth areas and we aim to maintain this momentum through the rest of this year and beyond. I'll now pass the call to Jeff.
Thanks, Mike. Good morning, everyone. I'll now review our financial performance for the first quarter of 2018, starting with revenues. As Michelle mentioned earlier, results for the first quarter were largely in growing 11% year over year or 15% excluding hemophilia. Let me now provide more detail on our MS franchise revenues.
While we experienced seasonality in greater than anticipated inventory impacts in the U. S, we believe the fundamentals of the business are healthy across our portfolio as we continue to drive stability in the U. S. And strong growth outside the U. S.
Global 1st quarter TechVadero revenues were $987,000,000, 3% increase versus the prior year. This included revenues of $729,000,000, a decrease of 3% versus Q1 2017, and $258,000,000 outside the U. S, an increase of 25% versus the first quarter of 2017. In the U. S, we saw an inventory drawdown of approximately $80,000,000.
This compares to a drawdown of approximately $60,000,000 in Q1 2017, us driving a difference of $20,000,000 year over year. Excluding this impact, U. S. TECFIDER revenues would have been stable versus Q1 of last year. As net pricing increases offset the impact of OCREVUS.
On a sequential basis, we saw stable U. S. Volumes for TECFIDERA versus the prior year. Accounting for the inventory dynamics, with improving demand generation trends within the quarter leading to increased share of new prescriptions and stable share of total prescriptions. In addition, we were very pleased with TECFIDER's performance outside the U.
S, driven by strong year over year patient growth across each large European market and solid emerging market growth, particularly in Japan, where Teck Vadera has reached 16% market share in its 1st year in the market. We believe and further geographic expansion into new markets such as Latin America. Ex U. S, TECFIDERA revenues benefited by approximately $12,000,000 versus the prior year, due to changes in foreign exchange rates net of hedging. Tesabri worldwide revenues were $462,000,000 this a decrease of 15% versus the first quarter of 2017.
This included $250,000,000 in the U S and $212,000,000 outside the U S. In the U. S, revenues declined 18% versus prior year, primarily due to the launch of OCREVUS and disproportionately higher gross to net charges driven by seasonality and timing. We saw stable U. S.
Volumes for TESSABRI versus prior quarter, with improving share of news prescriptions stable share of total prescriptions. Outside the U. S, TES Sabre Revenues decreased 11% versus the prior year. As a reminder, in Q1 2017, we recorded a $45,000,000 benefit following our agreement with the Italian National Medicines Agency, Afa, related to prior periods. Ex U.
S, Tysabri revenues this quarter benefited by approximately $17,000,000 versus the prior year due to changes in foreign exchange rates net of hedging. Tysabri patients increased in most major European markets versus the prior year, along with strong double digit patient growth in emerging markets. Interferon revenues, including both Avanix and PLEGRITY were $550,000,000 during the first quarter, a decrease of 15% versus Q1 'seventeen. This included $371,000,000 in the U S and $179,000,000 in sales outside the U S. In the U S, we saw a decrease of interference inventory of approximately $50,000,000 in Q1 twenty eighteen as compared to a decrease of $20,000,000, driving a $30,000,000 delta year over year due to channel dynamics.
Ex U. S. Interference revenues benefited by approximately $11,000,000 versus the prior year due to changes in foreign exchange rates net of hedging. Overall, U. S.
MS performance versus prior year was impacted by both the launch of OCREVUS and channel dynamics. Despite these factors, our U. S. Sales team demonstrate resilience and driving stability and underlying demand sequentially for TECFIDERA and TESSABRI. We expect both factors to be less significant on a year over year basis as we move throughout the year with a potential benefit is if there is a channel build towards the end of the year.
We are encouraged by the momentum we saw in underlying demand as we entered the 2nd quarter. Let me now move on to SPINRAZA. Global 1st quarter SPINRAZA revenues were $364,000,000. This included $188,000,000 in the U S and $176,000,000 outside the U S. We saw a 16% increase in the number of patients on therapy in the U S.
As compared to the end of the fourth quarter. However, revenues decreased versus Q4 due to a lower rate of new patient starts combined with the impact of the loading dose dynamics. We believe we have now worked through a good majority of the bolus of urgent infant and pediatric patients we saw earlier in the launch, and we continue to see significant growth opportunity in both pediatric and adult populations. We saw an increased contribution from maintenance doses as many patients have transitioned to dosing once every 4 months on a chronic basis. In the US, approximately 40% of SPINRAZA revenues in the first quarter were attributed to maintenance doses as compared to 25% in the 4th quarter.
This correlates with a continued decline in the average doses per patient from one 0.6 to one point one from Q4 last year to Q1 of this year. In the first quarter, approximately 20% of U. S. SPINRAZA units were dispensed through a free drug program, highlighting our goal that no patient will forego treatment because of financial limitation or an insurance denial in the U. S.
We believe Both inventory levels and discounts and allowances for SPINRAZA were relatively flat in the first quarter versus Q4 of last year. We continue to be encouraged by the opportunity to reach large number of untreated pediatric and adult patients in the U S. We expect to around lead patient identification, reimbursement and sales and marketing to reach older patients. Outside the U. S, the number of commercial SPINRAZA patients increased over 50% versus the prior quarter, and there are still approximately 290 patients active in the expanded access program.
We saw an increase in contribution from multiple markets, which recently secured reimbursement with over 2 thirds of ex U. S. SPINRAZA revenues in the first quarter coming from Germany, Japan, Italy and France. Overall, we believe that the international opportunity for SPINRAZA is even greater than in the U. S.
Given the uniform epidemiology across geographies and the growing level of market access that can generate future growth momentum. Let me now move on to our biosimilars business, which generated 128,000,000 of revenues this quarter, nearly doubling versus prior year. We have seen continued steady market share gains across the large European markets following the rapid initial conversion in the Nordics. In addition, to a continued expected uptake for Bene Poly. We believe the expected launch of IMRALDI in October of this year will be an additional growth driver for our biosimilars business going forward.
In the coming months, we plan to exercise our option to increase our equity stake Turning to our anti CD20 revenues, we recorded $443,000,000 in Q1, an increase of 30% versus the prior year, primarily driven by OCREVUS royalties as well as strong performance from Rituxan. This includes our estimated OCREVUS royalties of $77,000,000 for the first quarter. Total other revenues were $164,000,000 in the first quarter, an 83% increase versus Q1 2017 as we continued to benefit from greater contract manufacturing. Q1 GAAP and non GAAP gross margins were 86%, a slight improvement versus the 4th quarter, due to lower contract manufacturing and the impact of this embroider write off last quarter. Q1 GAAP and non GAAP RD expense was 16% of revenue or $497,000,000, including approximately $13,000,000 of trial closed out costs for ZumbraIDA.
There were no meaningful milestone payments in book booked in the first quarter. The increase in R and D compared to Q1 'seventeen was principally driven by higher clinical trial costs, as we invest the closing of our asset acquisition with Pfizer for BIV-one hundred and four. We also expect to record the substantial majority of the $375,000,000 upfront payment to IONIS as a both GAAP and non GAAP R and D expense, along with the equity premium as GAAP only R and D. Q1 GAAP SG and A was 16 percent of revenue or $501,000,000. Q1 non GAAP SG and A was also 16% of revenue at 498,000,000 As a percentage of revenues, both GAAP and non GAAP SG and A decreased versus the prior year, primarily due to the timing of spend across sales and marketing and G and A.
GAAP other net expense, which includes interest, was $41,000,000 in the first quarter versus $38,000,000 in Q1 of last year. Non GAAP other net expense was $35,000,000 in Q1 versus $38,000,000 in Q1 of last year. In Q1, our GAAP tax rate was approximately 22%, and our non GAAP tax rate was approximately 21%, both benefiting by approximately 250 to 300 basis points versus the prior year due to the recently enacted U. S. Corporate tax reform legislation, as well as the expected closing of the IONIS transaction and mix of profits by geography.
Our weighted average diluted share count for Q1 was approximately 212,000,000. We repurchased approximately 900,000 shares in Q1 for a total value of 250,000,000 leaving $2,750,000,000 remaining on our current share repurchase authorization, which now brings us to diluted earnings per share. In the first quarter, we booked GAAP earnings of $5.54 per share, an increase of 60% versus last year. And non GAAP earnings of $6.05 per share, an increase of 16% versus last year. We generated approximately $1,500,000,000 of cash flow from operations in Q1 and ended the quarter with approximately $7,100,000,000 in cash and marketable securities, and $5,900,000,000 in debt.
After repatriing $3,500,000,000 in Q1, approximately 85% of our cash is now held in U. S. We believe we have, and we will continue to have ample capacity to execute meaningful future business development M and A as well as return capital to shareholders. We will also continue to be disciplined in our approach and focused on value creation. I'll now turn the call back over to Michelle for his closing comments.
Thank you, Jeff. We closed the first quarter with solid double digit revenue and earnings growth and with the momentum across our business that we anticipated. In line with our strategic priorities, we allocated capital to both invest in our differentiated pipeline and opportunistically return capital to shareholders. We do not intend to pause or slow down here. We believe there will be plenty more we can accomplish through the rest of 2018.
Looking forward, within the next 12 months, we expect further progress across our neuroscience pipeline including completing enrollment of aducanumab, dosing the first patient with our gene therapy for SMA. Data readouts across MS, Alzheimer's, neuropathic pain of thalmorology and ALS. Initiation of Phase III studies in stroke and neuropathic pain and filing for regulatory approval in the U. S. For BIIB098 in MS.
Overall, as we have communicated in the past, our goal is to secure the long term growth potential of Biogen beyond just aducanumab. We believe we have made progress between the potential of 2019 U. S. Launch of B98, the potential launch of late stage assets for stroke PSP neuropathic pain in the early 2020s and our continued progress to bolster our early and mid stage pipeline but we clearly have more work to do to achieve this goal. Importantly and for the long term growth of Biogen, we are focused on our 8 priority markets with the U.
S. Remaining the most significant driver However, as we execute on our strategy and selectively expand our global footprint, we are seeing evidence that there is likely more long term growth opportunity than we expected in the EU and in the emerging markets. Our MS volumes continue to grow outside of the U. S, and it is still an under diagnosed disease in many developed countries. Our biosimilars business in Europe is now tracking at the potential run rate of at least $500,000,000 a year and we plan to launch IMRALDI in October of this year.
SPINRAZA is paving the way for Biogen to establish a presence in selected new geographies, which will support further global growth. In the first quarter, our ex US product revenues were $986,000,000, an increase of over 30% from the same period a year ago. And we have recently opened affiliates in China, Korea, Taiwan and Colombia. Finally, I want to reiterate our commitment to maximizing returns to our shareholders over the long term. These demands that we continue to allocate capital efficiently effectively and appropriately.
As we have demonstrated in the past, we will always strive to have an optimal capital structure as well as aim for superior returns from the investments we make. I would like to thank our employees around the world who have dedicated to making a positive impact on patient's life. And all of the physicians, caregivers and participants in our clinical development programs next month Biogen will be celebrating its fortieth anniversary. Our past and future achievement could not be realized without their passion and commitment. With that, we
Your first question today comes from the line of Omar Raffat with Evercore ISI.
I wanted to focus on Alzheimer's for a minute maybe and your sample size reestimation because of the higher variability. And I guess my question is this, you added patients to the trials despite lesser dropouts, which implies to me that perhaps the higher variance has to do with the assumptions you made on both the trials, both on the treatment effect and perhaps also on variance. So my question is, where are your assumptions on the placebo arm in formed by prior trials that have been reported large ones or were they more informed by the Phase 1b data that you presented previously?
Yes, Umer, this is Mike. I'll take that. So essentially you're correct about this. Let me clarify. The variability that was observed was and the powering of the study was initially designed based on our known data in the Phase 1b primate study as well as other previously conducted studies.
So both were contributing to our estimations of that. Of course, it's always an estimation of the variability that we would expect to see and the blinded sample size readjustment was put in place in order to take care of the situation where in fact our assumptions were not quite accurate. And that's what we found in this case where our assumptions as we've had initially going in, were not exactly the same as the behavior that we were observing across the blinded sample size. So as a consequence, we increased the sample size of the trial as a whole in order to preserve 90% power.
Got it. And just to be clear, when Lilly ran their 3rd trial, they used the higher end of the standard deviation and they basically took higher standard deviation from the first two trials. Is that a practice you guys continue to implement as well?
Well, I mean, we haven't gotten into that level of detail on exactly the statistics underlying our initial assumptions. But I but just for a little bit of perspective, I mean, this blinded sample size reestimation, as you know, is a pretty standard method used in trials. And we did the same thing an increase of sample size for both our TECFIDERA and PLEGRITY trials and they were ongoing.
And your next question comes from the line of Geoff Meacham with Barclays. Please go ahead.
I just had a question on commercial SPINRAZA. I realize that trends can be lumpy on a sequential basis. I'm just given dosing, but
It does look like
new starts moderate in the U. S. Can you speak to the dynamics in the U. S. End of the market?
And then obviously OUS, you do have some nice sequential growth and good new adds and maybe just speak to kind of where you are with the with respect to adoption and some of the some of the major market Thank you.
So thanks for the question. This is Michel. We don't see the start forms really at the trend line, and we are working hard really to capture now the rest of the pediatric population and the adult population, and this takes a bit more time than we anticipated. But if we step back There was a bonus of patients a year ago that were working for this, for this only hope for treating SMA. And they came pretty fast to treatment and we have basically outpaced all estimate that we had and that the external stakeholders had also.
So we did extremely well, and the model worked very well. Now the 2nd phase is absolutely to do to ready to do the same, but for the pediatric and adult population, this is the biggest data of SMA patients. So we are basically enhancing and increasing the field team. We have now an adult campaign we are launching and we start to see traction. We have patients ambassadors as adults and we are encouraged by the momentum actually.
So we are really focused on implementation. There is still more than 5000 patients to go. The team is putting the head down and implementing better than ever. And actually, I have good confidence in our US team.
Your next question comes from the line of Eric Schmidt with Cowen. Please go ahead. Maybe another question for Michelle on Bizdev. You mentioned a renewed focus here. Is there a specific goal that you're trying to achieve via business development.
Maybe you can comment on what that is and what exactly you and the board have alignment on with regard to your focus here.
So let me take that one. This is Jeff. So as Michelle had said and I've said as well, we've got, an enviable position here where we were well capitalized and we generate a lot of cash. And so we're in an enviable position where we have a lot of cash available to create shareholder value. Our premium is on adding to the pipeline, given our commercial footprint and our manufacturing footprint and trying to bring in assets that are closer to being market ready.
So there's certainly a preference to kind of look at those types of transactions. However, as we go along, we'll continue to add to the pipeline with mid stage assets and real estate assets where they fill in and Mike's done a great job with his team doing that. But at the same time, given our capital situation or cash flow generation, we can both add to the pipeline, both later stage assets and mid stage assets and also return capital to shareholders. And I do want to reiterate we have $2,750,000,000 remaining under our share repurchase program, and we expect to be active on that front as well.
So if I can add on Jeff's comment, the priority, capital allocation will go in terms of BD, we go on the priority growth areas. So we will retain some capital and we distribute will continue to distribute the way we have done, but even more eventually. But the investment in terms of BD will be primarily dedicated to the priority growth areas: MS, neuroimmunology, movement disorders, neuromuscular diseases, And the last one, Mike?
Alzheimer's disease.
Alzheimer's disease, absolutely.
Your next question comes from the line of Cory Kasimov with JPMorgan. Please go ahead.
Hey guys, good morning. Thanks for taking the question. I guess following up on, on Eric's, I also wanted to ask about BD, but in a different way, as it relates to the growth outlook for the company from here. So with SPINRAZA flattening out, at least in the U. S.
As you've been predicting, and a stable MS franchise. I'm curious if you think you can continue to grow the business over the intermediate term without bringing in a later stage pipeline from the outside? Thanks.
Let me start with, with, with the comment on MS, spinraza flattening out in the U. S. I don't think we're saying that the U. S. Is going to flatten out indefinitely.
I think what we're saying is because we were so successful in getting through the bolus of patients when we first introduced the drug, that we had kind of a benefit, one time benefit of a number of patients. Particularly in kind of the infants and the pediatrics. And so we've worked our way through that, which is why kind of the loading doses have come down a bit, which is kind of, impacting our sequential growth. We think that as we, as Michelle said, penetrated the adult segment, which is the largest segment, that growth will resume, and we're kind of predicting that to happen at kind of the end of this year as our sales force gets focused on the different centers that treat adults. We get through reimbursement.
We identify those patients. So There's still a very good growth opportunity in the U. S. Outside the U. S, there's an even bigger opportunity.
And you can see, and we've said clearly that we think the market's gonna greater, we won't face exactly the same dynamics because some of the outside U. S. Patients don't go through the normal loading, doses. They come through the expanded access program. So we'll have more of a regular growth, outside the U.
S. So we're still very confident, that the SPINRAZA has a very growth, a good growth opportunity ahead of it.
So I can only reinforce the focus of the organization on executing well all around the world, including in the as I said, we are very encouraged by the leadership and the implementation that we see in the US. Even if there are some bumps, sometimes on the way, this is the nature of our business. So it's all about growth and this hopefully will be generated in the U. S. More more directly but mostly ex U.
S concerning SPINRAZA with the rapid and sequential reimbursement that we are gaining and the objective by the end of the year, we are unlocking new opportunities in terms of treating SMA population. So this paves the way hopefully us achieving the peak sales that we anticipate. And we always said this will be one of the largest asset of the organization. Obviously, we look at complementing eventually the momentum with some acquisition, but we'll be very wise always on the way we invest our capital. And if we believe we can do these assets can do better in Biogen hands, then we will propose that to the board.
But we'll be always very cautious, but we are actively looking absolutely.
Your next question comes from the line of Jeffrey Porges with Leerink.
Appreciate all the color. Just following up on SPINRAZA, you gave us good information on the distribution of patient types by age in the U. S, but could you provide the same color for the 2300 or so patients, outside the U. S. I think that's the right number.
And then could you just comment on treatment systems in the U. S. Where you've been in the market for longest, for those 3 different patient populations infant pediatric and adolescents and adults? Thanks. Yes.
So let me give you the numbers as it relates to kind of Europe. I don't have all the numbers around the world, but kind of our type 1 patients for roughly 810 in the first quarter, type 2 or 590 and type 3 were 138. That's how it breaks out EU plus, Jeff.
Your next question comes from the line of Michael Yee with Jefferies. Please go ahead.
Thanks for the question. Appreciate it. In regards to the Samsung BioEP of which you made a comment about planning to exercise in the coming months. Can you just remind us, I guess, how that would work you do that, do you have to integrate to your P and L? Are you just going to hold the equity stake?
Obviously, that would be worth 1,000,000,000 of dollars. So maybe just the plans on that and how that strategically would fit with what you guys are trying to do, etcetera, etcetera? Thanks so much.
So this is Michel before we come to this question. I just wanted to answer the second part of the question. The discontinuations on SPINRAZA are extremely low. And this speaks to the efficacy of the product and the progress that the patients are making on the product. Now value signals.
Yes. So as it relates to kind of exercising that option, that would be an equity investment we'd make I would still be below the level that would acquire us to consolidate. So it would be an equity investment where we would just pick up their share or our share of the net profit. With regard to that collaboration. So it would be booked kind of below the line, below non operating.
Your next question comes from the line
Hi, thanks for the questions. Another quick one on SPINRAZA as well. You mentioned previously that 7 patients from the AveXis-one hundred and one Phase 1 trial in type SMA patients have already been receiving SPINRAZA treatment. Can you talk about whether those 7 patients saw additional function improvement, from AstraZeneca. And then secondly, in light of the recent failures of the Merck basing inhibitor in 2 Phase III trials, does that change your thought on your base program in Phase III or not?
Thank you.
Ying, this is Mike. Thanks for the questions there. I mean, so the short answer is that we really don't have direct information on the clinical status or outcome of the patients in the AveXis trial that had subsequently gone on SPINRAZA. All we can really say is that medical experience to date and as reported by AveXis, indicates that number or a large number of patients who receive gene therapy has subsequently gone into SPINRAZA. But while we don't know the exact reasons, there they're not hard to imagine.
And in any event, suggests that even with a gene therapy product on the market, we can anticipate substantial needed use for combination therapy, which is something that we're actively exploring in terms of preclinical studies. With regard to the Merck base inhibitor results, of course, these are things that we've been looking at very carefully. I think they do raise a number of very valid questions about the right patient population study design when you might anticipate potential benefit or not. And these are things that we're looking at very closely in active discussions with our collaboration partner, Eisai.
Your next question comes from the line of Matthew Harrison with Morgan Stanley. Please go ahead.
Great. Good morning. Thanks for taking the question. I was hoping maybe we could just talk a little bit about your neuropathic pain assets. Obviously, you're going to have some probably have some data from the radiculopathy study sometime in the second half of this year.
Maybe you could just help us think about what we're going to see out of that data set and how you would frame that data in terms of insights into the overall program? Thanks.
Yes, so this is, this is Mike. Matthew, thanks for the question on that. So, right now, this is we've got BIIB74. It's we'll be starting its phase 3 trial in trigeminal neuralgia as I mentioned. It's completed enrollment in the phase 2 study in painful lymphocyticulopathy.
These are 2 different, pain syndromes, I think as you know, and one of the challenges and opportunities in the neuropathic pain space is that you've got a variety of different specific indications that have different features of neuropathic pain, trigeminal neuralgia, very episodic pain crises and somewhere we've got strong proof of concept data. Lumbosacral radiculopathy or sciatica, this is a little bit more of a mix neuropathic inflammatory pain state. That's a little bit more of a mix mixture. We've started screening on our on our on a trial in small fiber neuropathy, again, this would be a small fiber, more episodic pain disease. In each of these cases, a lot depends on the specific pain state and the mechanism that you're going after.
That's why we were trying in each of these 3. The strongest clinical evidence that we have to date is in trigeminal neuralgia and we're looking to explore where that might provide additional benefit beyond trigeminal neuralgia.
Your next question from the line of Terence Flynn with Goldman Sachs. Please go ahead.
Hi, thanks for taking the questions. Maybe just on in ROSA in Europe. I was wondering if you can give us a little bit more detail on the percent of patients that are getting a loading versus maintenance dosing and then roughly where you'd expect that to end up by the end of the year. And then for Jeff, you had repurchased $250,000,000 of stock in the quarter. You've mentioned you still have a pretty sizable amount out outstanding.
How should we think about the pace on the forward there? Thanks a lot.
So I will get started on the SMA question ex U. S. So you recall that we had many patients on the early access program. So we don't have the the hockey stick and the bolus of the dosing dose in most of the market. So this is helping the trend be much more smooth And in addition, David, the sequential access and reimbursement progress we are making, and this should pave the way combined with the US performance for long term growth on SPINRAZA.
And with regard to the share repurchase, question. So I would look based on the stock price today, we think the company is very undervalued. I would look for us to kind of pick up our pace with regard to the share repurchase, and actively to get at the $2,750,000,000 over a reasonable time frame.
Your next question comes from the line of Alethia Young with Credit Suisse.
Thanks for taking my question. I was just curious actually about the Alkermes program BIIB098. Just how you're thinking about the potential opportunity there from the from the relationship of payers and physicians in thinking about differentiated profile and to TECFIDERA, in particular, the Galenia generic may come in August of 2019? Thanks.
Okay. Alicia, this is Mike. I'll start with this and then pass it on a little bit. I mean, the status is that, Alkermes is presenting data at AAN, demonstrating clear benefits I mentioned on annualized relapse rate and MRI lesions where in the midst of generating and gathering data in head to head, comparison with TECFIDERA which we'll be talking about more at the beginning of next year. We do anticipate being able to file this year And, look, the profile that we're looking for here is, to date, we've seen strong evidence of efficacy We've seen a safety profile that looks favorable and we're very interested to know how that lines up relative to our experience with TECFIDERA.
And we imagine that upon filing, and making this available to patients that this would provide an additional potential option with potentially differentiated tolerability profiles.
And if I may add, this is Michel. This will be another opportunity to expand the fastest growing segment of the MS DM keys, which is the orals. And TECFIDERA is doing great. But here we'll have another opportunity with potentially an upgrade. And coming back to the overall growth questions, and the reasons to believe also for MS, we continue to take price and we have seen that the generics are mostly impacting the originator.
The unmet medical need is tremendous we have an entire portfolio where we are leaders on the platforms, the orals and the high efficacy. We are generating more data and we have a pipeline. So these are additional reasons to believe in our ability to compete and to grow.
And your next question comes from the line of Robin Karnauskas with Citi. Please go ahead.
Hi, guys. Thanks for taking the question. So just a little bit along the lines of TECFIDERA thinking about next year. You were hearing from some doctors that they view TECFIDERA and Gilenya very similarly. And so, typically patients don't get both.
I was curious whether or not your market research was supportive of that. And then on the lines, if you think that a generic will really only impact the brand, what gives you the confidence? Is it just the rebating? And would you be surprised if there is going forward next year there would be stuff added and people to use a generic, ahead of a different type of brand in the oral class. Just maybe give us some comfort around what your market research is telling you.
So the way the market so far has managed those DMTs was with open formularies because of this type of disease. And they do believe the payer that it's not a blanket formulary that will increase the value for the patients. We are talking here about a radically different therapies, different classes. As you know, the monitoring on the Gilenya is pretty intense during the first period on the product. I don't see how evidence based medicines will be completely overshadowed by formularies in order to prescribe 1st a generic of S1P that has his baggage of efficacy and risk profile that is different from the other DMTs.
This would be a bad day for evidence based medicine in this country And this will be a first time for neurological diseases and mostly MS. I don't see that as a credible assumption, we will not take that in
with practicing neurologists out there is that there would be a very strong aversion we believe to patients potentially having to have a multi hour first dose cardiac monitoring as a step through, for some other therapy. So there is an initial, a clinical burden that would generally be viewed negatively by a number of MS neurologists, we believe.
And your final question today will come from the line of Ronny Gal with Bernstein. Please go ahead.
Good morning, everybody, and thanks for fitting me in. Just want to talk a little bit about the pattern of buying that you're seeing with the AMS product. It feels a little bit like, buyers are mining in the fourth quarter ahead of anticipated price increases in the first quarter. Is this what's going on? And this is something, is this something you can manage through contracting?
And similarly, Can you talk a little bit about co pay accumulators and have you switched your patients from content insurance type card to more of a credit card format? In terms of your co pay assistance program?
Ryan, it's Jeff. Well, let me help you with the inventory channel dynamics and reiterate some of the numbers for you. So I think as you saw in our press release, we disclosed the channel inventory overall for, U. S. MS came down about 130,000,000 in the first quarter.
If you look at that compared to the fourth quarter, channel inventory went up $50,000,000. So we had about $180,000,000 swing has nothing to do with fundamental demand. As far as we can see, it's just a channel dynamic. So that's a good kind of overall sense of kind of what happened Q4 to Q1. And we suspect that the case is, in fact, because of expected price increases we've done them fairly regularly in the first quarter.
So that, that we can't control to a certain degree, that we have kind of a larger, kind of channel building, that's their prerogative in the fourth quarter. And some drawdown in the first quarter. Fundamentally though, as we look at kind of share, and we looked at it carefully with regard to kind of going from the 4th 4th to 1st quarter, as I said in the script, you know, we believe we picked up share, in both, Tecodera and Tysabri from the fourth quarter to 1st quarter in the U. S. In terms of new prescriptions and the kind of flat in total prescriptions.
So we think the business underlying are pretty healthy. It's going in the right direction, but we can't always kind of the channel inventory dynamics?
Yes, we are pleased to see that basically we crossed back during the month of March. In NBRx OCREVUS with a growth momentum for the B portfolio. So we are pleased to see that, but still a long way to go. So concerning the patient accumulator, I understand this is the last question. So, we believe that some TPMs have started to account the co pays elements differently according to to this new copay evaluator formula, there is absolutely no impact at this stage.
We need to monitor that very carefully, but at this stage, there is nothing more to report. So thank you all for attending our Q1 call and have a good day. Thank you.
Thank you to everyone for attending today.