Biogen Inc

NASDAQ:BIIB

Earnings Call Transcript 2018-Q4

[Operator]

Good morning. My name is Jack, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen Fourth Quarter and Full Year 2018 Financial Results and Business Update Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions] Please limit yourself to one question to allow other participants time for questions. [Operator Instructions]

Thank you. I would now like to turn the conference over to Mr. Matt Calistri, Vice President, Investor Relations. You may begin your conference.

[Matt Calistri, Vice President, Investor Relations]

Thank you and welcome to Biogen's fourth quarter 2018 earnings conference call. Before we begin, I encourage everyone to go to the Investors section of biogen.com to find the earnings release and related financial tables, including a reconciliation of the GAAP to non-GAAP financial measures that we will discuss today. Our GAAP financials are provided in Tables 1 and 2. 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 that follow 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 am joined by our Chief Executive Officer, Michel Vounatsos; Dr. Michael Ehlers, EVP of Research and Development; and our CFO, Jeff Capello. We will also be joined for the Q&A portion of the call by our Chief Medical Officer, Dr. Al Sandrock.

Before I conclude, I would also like to remind everyone, that we now post releases related to earnings calls 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 do this instead of publishing earnings releases and any releases related to Investor Events and earnings calls via Newswire services. Our Twitter handle is @biogen.

Now, I will turn the call over to Michel.

[Michel Vounatsos, Chief Executive Officer]

Good morning, everyone, and thank you for joining us. First let me start with some financial highlights. Biogen closed 2018 with an all-time high in quarterly revenues of $3.5 billion, an increase of approximately 7% compared to the same period a year ago.

For the full year 2018, Biogen generated another all-time high of $13.5 billion in revenues, representing growth of 10% year-over-year. Full year 2018 GAAP earnings were $21.58 a share, an 81% increase versus full year 2017. Full year 2018 non-GAAP earnings were $26.20 a share, a 20% increase versus full year 2017. We are pleased with this strong year-over-year growth as we continue to execute on our strategy to solidify our long-term leadership position in neuroscience.

Now, let me review the year. First, full year MS revenues including OCREVUS royalties were $9.1 billion demonstrating resilience. The number of patients on our MS products globally remained relatively stable versus the prior year. Importantly, we continued to see improving trends for our MS business in the U.S. on a year-over-year basis.

Second, SPINRAZA, which we pioneered in collaboration with Ionis as the first treatment for SMA, generated full year global revenues of $1.7 billion, and nearly double the revenues we delivered in 2017. This blockbuster performance was driven by strong year-over-year revenue growth in the U.S. and even greater revenue growth outside of the U.S.

Over the past year, including the expanded access programs and clinical trials, we have more than doubled the number of patients on SPINRAZA to over 6,600 patients. SPINRAZA is the standard of care in SMA with approval in over 40 countries and formal reimbursement in 30 countries.

Third, we continue to expand and progress our neuroscience pipeline with strong momentum, building depth in our core growth areas. We are leveraging the interconnectivity within neuroscience as we aim to create multiple franchises beyond MS, SMA, and Alzheimer's disease.

2018 was one of the most productive years we have had in research and development as we aim to further de-risk our pipeline and prepare for multiple potential launches in the early 2020s.

Starting with our core growth areas, we made significant progress in our MS pipeline including an NDA submission to the FDA, initiating new life cycle management initiatives, and increasing investment in our R&D portfolio to develop potentially transformative new treatments, which Mike will discuss in more details. In Alzheimer's and dementia, we completed Phase 3 enrollment of aducanumab. We initiated a Phase 2 study of BIIB092 in Alzheimer's disease, and we announced topline results of BAN2401 with our partner Eisai.

In neuromuscular disorders, we made impressive progress building depth. We acquired BIIB110, a muscle enhancement program from AliveGen. We initiated a Phase 1 study of BIIB078 targeting C9orf in ALS, and we announced positive Phase 1 interim results for BIIBO67 in SOD1 ALS. In movement disorders, we created strong momentum. We initiated a Phase 2 study of BIIB054 in Parkinson's disease, and we completed enrollment of our Phase 2 study of BIIB092 in PSP.

In our emerging growth areas of acute neurology, neurocognitive disorders, and pain, we did initiate four new studies. We expanded our pipeline with the addition of BIIB104 for cognitive impairment associated with schizophrenia and our option for TMS-007 for acute ischemic stroke. We are also advancing the program -- the Phase 3 program for BIIB093 in large hemispheric infarction with a potential to generate peak revenues of over $1 billion with initial launches as early as 2022.

Moving on to our biosimilars business. Full year biosimilars revenues were $545 million, which represents 44% growth year-over-year. In the fourth quarter, we launched IMRALDI, our adalimumab biosimilar referencing Humira in several European markets. IMRALDI has generated $17 million in revenues since its launch in mid-October, making it our most successful first quarter launch of a biosimilar.

Importantly, our cash generation remained very strong and continued to provide us with significant optionality and flexibility to allocate capital. In 2018, we spent a total of approximately $1.8 billion through six business [ph] development deals and the increase in our share of the Samsung Bioepis joint venture.

We continue to diligently evaluate new opportunities for more potential business development and M&A. We also repurchased approximately 14.8 million shares for $4.4 billion, and we have about $2 billion remaining in our share repurchase program.

In addition, we began 2019 with a new collaboration with Skyhawk Therapeutics with the aim of developing oral splicing modulator for multiple diseases, including MS and SMA. We continue to be financially disciplined, and we are focused on implementing a lean and simple operating model with the goal of continuous operational improvements.

As we have demonstrated in the past, we are committed to maximizing returns for our shareholders while continuing to bring innovative therapies to patients, something that demands a thoughtful approach towards all our investments over both the short term and long term.

In summary, 2018 was clearly a very productive and successful year for Biogen, as we executed on our strategy and continued to deliver noticeable progress. Our core MS business demonstrated resilience, SPINRAZA continued to grow in the U.S. and even more outside of the U.S., and we remain committed to our goal of being the long-term standard of care in SMA.

We expanded and progressed our pipeline by adding six new clinical programs and completing enrollment of three late-stage studies. We grew our biosimilar business and launched IMRALDI in Europe. We are actively implementing a leaner and simpler operating model, and we are generating ample cash as we focus on strategically allocating capital to develop and build depth in our neuroscience portfolio, again with a goal of maximizing shareholder returns and bringing innovative therapies to patients.

Overall, we continue to make progress towards our goal of building a multi-franchise neuroscience portfolio, and we are very excited about our upcoming data readouts.

I would now turn the call over to Mike for a more detailed update on our recent progress in R&D.

[Michael Ehlers]

Thank you, Michel, and good morning, everyone. Neuroscience is experiencing a revolution in science and medicine. There is no a large area of unmet needs and disease in the nervous system, and we believe that our focus on neuroscience offers a key strategic advantage.

Before I discuss our pipeline in more detail, let me comment on our recent progress on building a multi-franchise neuroscience portfolio, supported by a broad range of therapeutic modalities.

Complementing our expanded collaboration with Ionis delivers their antisense oligonucleotide platforms. Earlier this month, we announced a strategic set of collaborations with C4 Therapeutics and Skyhawk Therapeutics to discover and develop novels, small molecule approaches for neurological diseases.

Our collaboration with C4 Therapeutics, we utilize C4's platform to discover small molecules and engage the endogenous ubiquitin–proteasome system to selectively tag disease-causing potential for degradation.

And through our collaboration with Skyhawk, we aim to discover small molecules capable of modulating RNA splicing at selective pre-messenger RNAs, including SMN2.

With these collaborations, we have further expanded the breadth of modalities we are pursuing, which now includes biologics, antisense oligonucleotide, oral protein degraders and splicing modulators and gene therapy.

As Michel discussed, looking over 2018, we added six clinical programs to our pipeline and transitioned five pipeline candidates from research to development. The same number as the previous year, which nearly doubled Biogen's historical productivity. Thus, once again, 2018 represented a substantial enhancement of our differentiated clinical portfolio of potential breakthrough medicines.

Turning to advances in the fourth quarter. Let me start with the depth, we are building in neuromuscular disorders. Last month, we, along with our partner Ionis, received data from an interim analysis of the Phase 1 study of BIIB067 in the form of familial ALS.

BIIB067 is antigens oligonucleotide, targeting superoxide dismutase 1 or SOD1, mutations in which confer a toxic gain of function and cause a familial form of ALS that constitutes approximately 2% of all ALS cases. This interim analysis demonstrated both proof-of-biology and proof-of-concept with the concordance across multiple clinical and biomarker endpoints.

Specifically, at the highest dose tested, we saw a statistically significant lowering of SOD1 protein in the CSF with the p-value of 0.002 and a trend towards lowering of CSF neurofilament, a biomarker of axonal injury.

And we observed a numerical trend across three dimensions of clinical efficacy, consistent with the potentially meaningful clinical benefit as compared to placebo. Specifically, we observed swelling of clinical decline as measured using the ALS Functional Rating Scale, slowing of decline in respiratory function as measured by slow vital capacity and slowing of decline in muscle strength as measured by handheld dynamometry.

Based on these positive data, we plan to add an additional cohort to the study to further evaluate the highest dose. With very limited treatment options for this devastating genetic form of ALS, we believe this additional cohort could provide important new data to support the rapid path to registration.

More broadly, we believe that these data have positive implications for additional antisense oligonucleotides in our pipeline, including BIIB078, which targets C9ORF72, BIIB080, which targets tau and up to two antisense oligonucleotides -- in clinic this year.

Additionally, we believe that these data exemplify the depth we are building in neuromuscular disorders, including ALS and highlight the interconnectivity across our pipeline.

Turning to SMA, as a leader in the space, we welcome additional therapeutic options for patients, including the potential launch of Novartis gene therapy, AVXS-101, which we believe will be initially indicated for infants.

A number of questions remain for this experimental approach as data on the safety, efficacy and durability of AVXS-101 remain limited with the results reported to date for only 15 patients followed for up to 2.5 years, seven of whom are reported to have subsequently initiated treatment with SPINRAZA.

This is, in contrast, to the SPINRAZA clinical trial program, which has included more than 300 patients followed for up to six years. It is important to note that there are significant differences in the age and severity of the patient population between the Sham Control ENDEAR study of SPINRAZA and the Phase 1 open-label study of AVXS-101.

We believe that earlier treatment initiation positively impacts the clinical efficacy of agents designed to boost full length SMN protein production. Patients in the ENDEAR study were older with the mean age at first dose of 5.3 months, whereas participants in the Phase 1 open-label study of AVXS-101 initiated treatment earlier with a mean age of first dose of 3.4 months. Thus direct comparisons between these data sets are not scientifically valid.

In addition to ENDEAR, we are very encouraged by the data from the NURTURE study of SPINRAZA in presymptomatic infants which shows patients on average achieving motor milestones consistent or nearly consistent with normal development. We believe these data, combined with the real world reports of significant efficacy across all patient types and ages, supports SPINRAZA remaining the standard-of-care in SMA even after the introduction of alternative modalities.

Turning to MS and neuroimmunology. Biogen strategy to extend our leadership position in MS has focused on three strategic imperatives. First is the pursuit of next-generation therapies for relapsing form of MS while also advancing life cycle management for our current portfolio. Second, we aim to advance the care of progressive forms of MS by leveraging emerging insights and new drug targets. Third, we aim to slow or reverse disability progression and restore function through remyelination and excellent repair or protection.

As Michel discussed, we've made significant progress this quarter across these imperatives, including submitting the NDA for diroximel fumarate, or VUMERITY, in the U.S. with head-to-head data versus TECFIDERA expected mid-year; reinitiating development of BIIBO61, a small molecule remyelination agent; dosing the first patient in the NOVA study; examining the efficacy of extended interval dosing of TYSABRI; and dosing the first patient in a bioequivalent study of intramuscular formulation of PLEGRIDY. For more details on each of these programs I encourage you to review our MS Investor Webcast held on December 12 of last year, which is available on our website.

We also had exciting new developments with our industry-leading Alzheimer's disease and dementia portfolio. At the Clinical Trials on Alzheimer's Disease Meeting, or CTAD, we presented updated analysis of the long-term extension of the Phase 1b PRIME study of aducanumab which were generally consistent with previous analysis. In addition, there were no changes to the risk-benefit profile of aducanumab.

We also showed data from the PRIME study suggesting that following treatment with aducanumab, the reduction in brain amyloid correlates with slowing of clinical decline. We expect final data from ENGAGE in EMERGE, the Phase 3 studies of aducanumab in early 2020.

Also at CTAD, our collaboration partner Eisai presented additional analysis of the Phase 2 study of BAN2401. Data from pre-specified subgroup analysis showed that treatment with BAN2401 was associated with the reduction in brain amyloid as well as clinical benefit across subgroups of APOE genotype, clinical stage and concomitant use of AD medications.

Importantly, while the study was not powered to show statistical significance in subgroup analysis, we believe there was evidence of clinical benefit in both APOE for carriers and non-carriers with small sample sizes potentially explaining the numerical differences in clinical efficacy between these subgroups.

Overall, we continue to believe that the data from BAN2401 increases the probability of success for both this asset as well as aducanumab. BAN2401 and aducanumab share important features, distinguishing them from other anti-beta amyloid anybodies including specificity for binding aggregated forms of beta amyloid, full effector function, which we believe is important for inducing amyloid clearance by microglia, data demonstrating robust removal of amyloid plaque in humans and signals a potentially clinically meaningful slowing of cognitive decline across multiple measures. To our knowledge, amongst clinical a-beta antibodies only aducanumab and BAN2401 share these features.

Together with Eisai, we are pursuing a large Phase 3 studies to confirm these findings including the planned initiation of a Phase 3 study of BAN2401 following the conclusion of ongoing regulatory dialogues. Eisai also presented safety and efficacy data from the Phase 2 study of elenbecestat, a small molecule base inhibitor being evaluated in two Phase 3 studies and in response to external data presented at CTAD suggesting that treatment with other base inhibitors has been associated with trends toward cognitive worsening, a cognitive safety monitoring plan has been implemented in the ongoing elenbecestat studies to ensure that patient safety is paramount.

The independent Data Monitoring Committee has reviewed data from the Phase 3 studies and recommended that the studies proceed and we will continue to monitor safety, including cognitive safety, as the study progresses. Finally, given the evidence that the beta-amyloid pathology begins to accumulate in the brain decades prior to the clinical onset of Alzheimer's disease, I am pleased to announce that we along with our partner Eisai are planning to initiate a Phase 3 study to evaluate whether early use of aducanumab can prevent or delay the clinical onset of Alzheimer's disease.

The study will include patients with evidence of amyloid pathology in the brain with or without subjective cognitive complaints. This represents an earlier phase of the disease, demonstrating studies in ENGAGE and EMERGE and is otherwise referred to as Stages 1 and 2 in the FDA draft guidance on treatment of early Alzheimer’s disease. We look forward to sharing more details about this study in the near future.

Moving to our progress in neuropathic pain. In October, we indicated that we have paused the initiation of the Phase 3 program of vixotrigine or BIIB074 in the state and use-dependent voltage-gated sodium channel blocker in trigeminal neuralgia.

Now, based on recent feedback from the FDA, I am pleased to say that we are planning to initiate a Phase 3 program for the development of vixotrigine in trigeminal neuralgia by the end of the year. And in parallel, we continue to enroll a Phase 2 study of vixotrigine for small fiber neuropathy.

Within neurocognitive disorders, last month we dosed the patient in the Phase 2b study of BIIB104 for the treatment of cognitive impairment associated with schizophrenia. BIIB104 is a first-in-class AMPA receptor potentiator that we believe has compelling data from a number of distinct early clinical studies, demonstrating functional circuit activation as measured by fMRI, treatment effects on relevant domains of cognitions such as working memory, short-term memory, verbal recall and reasoning, and the potential for favorable benefit risk profile.

Broadly speaking, we believe neurocognitive impairment is a central node in the network of symptomatology that defines many neurological diseases. Therefore, we believe BIIB104 may have potential applicability in multiple diseases within our core and emerging growth areas.

As we strive to be the neuroscience leader, we continue to prioritize our activities and build depth in what we believe are our most promising programs and disease areas. With that in mind, last month we made the strategy decision to terminate our collaboration with AGTC to develop AAV-based gene therapies for X-linked retinoschisis or XLRS and X-linked retinitis pigmentosa or XLRP based in part on recent clinical data in XLRS.

We have also decided to terminate specific programs included in our collaboration with the University of Pennsylvania. To be clear, our SMA gene therapy program with UPenn, which remains on clinical hold with the FDA, is not affected by this decision.

Overall, Biogen R&D delivered significant progress in 2018. We believe we are in a strong position today with four programs in Phase 3, 13 in Phase 2, and seven in Phase 1 with the deep pre-clinical pipeline across multiple modalities and we continue to generate clinical data that reinforce our commitment to neuroscience and the intrinsic interconnectivity of the space.

For instance, we believe our recent positive date on BIIB067 in SOD1 ALS, resonate across our pipeline, supporting the depth we are building in ALS and highlighting the promise of our collaboration with Ionis to leverage the antisense oligonucleotide platform across a range of neurological disorders.

And we don't stop there. To realize our vision of becoming the definitive leader in neuroscience, we look forward to continuing to invest in and advance our pipeline in asymmetric capabilities with the goal of developing innovative medicines with the potential to transform the lives of patients living with devastating neurological diseases.

I will now pass the call to Jeff.

[Jeff Capello, Chief Financial Officer]

Thanks, Mike. Good morning, everyone. Let me now provide some detail on our financial performance for 2018 and share with you our guidance for 2019.

Let's start with revenues. As Michel mentioned earlier, we had a strong Q4 2018 from a revenue perspective. Total revenue for the fourth quarter grew 7% year-over-year or approximately $3.5 billion and grew 10% for the full year to $13.5 billion.

Overall, our MS business delivered revenues of $2.3 billion in the fourth quarter of 2018, including OCREVUS royalties for approximately $152 million. MS revenues in the fourth quarter of 2018 decreased 1% versus the prior year without OCREVUS royalties and increased 2% including OCREVUS royalties.

In the U.S. MS revenues in the fourth quarter 2018 benefited from channel inventory build for approximately $115 million, compared to a build of approximately $15 million in Q4, 2017.

Our U.S. business continued to show signs of stabilization in the fourth quarter, continuing the trends of improving year-over-year performance we saw throughout 2018.

Full year MS revenues were $9.1 billion including OCREVUS royalties of approximately $478 million, representing a decrease of less than 1% versus the prior year. Excluding OCREVUS royalties, MS revenue decreased 4% versus the prior year. Full year 2018 MS revenues benefited by approximately $86 million versus the prior year due to changes in foreign exchange rates, net of hedging.

Global fourth quarter TECFIDERA revenues were $1.1 billion, a 3% increase versus the prior year. This included revenues of $856 million in the U.S., an increase of 3% versus the fourth quarter 2017 and $254 million outside the U.S., an increase of 4% versus the fourth quarter of 2017.

TECFIDERA benefited from increase in channel inventory in U.S. of approximately $65 million in the fourth quarter 2018 compared to an increase of approximately $40 million in Q4 2017. We were pleased to see continued relative stability in new prescriptions in U.S. as we have now anniversaried the launch of OCREVUS.

Outside the U.S., we performed very well in Q4 2018 with double-digit volumes increases in Europe and Japan versus the prior year. Somewhat offset by pricing pressures in several European countries. For the full year, worldwide TECFIDERA revenues were $4.3 billion, an increase of 1% versus prior year. This included $3.3 billion in the U.S. and $1 billion in sales outside the U.S.

The Interferon revenues including both AVONEX and PLEGRIDY were $597 during the fourth quarter, a decrease of 7% versus of Q4 2017 due to continued shift from the injectable platforms to oral or high-efficiency therapies. This included $4.31 million in the U.S. and $166 million in sales outside the U.S. Within the U.S.

AVONEX and PLEGRIDY benefited from the channel inventory build for approximately $40 million compared to a build of approximately $10 million in the fourth quarter of 2017. For the full year, worldwide Interferon revenues were $2.4 billion, consisted of $1.7 billion in the U. S. and $695 million in sales outside the U.S.

TYSABRI worldwide revenues were $464 million this quarter, stable versus the fourth quarter of 2017. This included $257 million in the U.S. and $208 million outside the U.S. In the U.S. revenues increased 2% versus of the prior year. Within the U.S. TYSABRI benefited from a channel inventory build of approximately $10 million compared to relatively stable inventory levels in the fourth quarter 2017.

Within the fourth quarter, we saw continued improvement in TYSABRI performance in the U. S. with the highest new prescription share since the launch of OCREVUS. Outside the U.S. TYSABRI revenue increased 1% versus the prior year. For the full year, worldwide TYSABRI revenues were approximately $1.9 billion, a decrease of 6% versus the prior year, primarily due to the launch of OCREVUS. We recorded U.S. revenues of $1 billion in the U.S. and $839 million internationally.

As expected across our MS business, we saw an increased discounts and allowances in the U.S. in the fourth quarter, primarily due to seasonality. Throughout 2019, we expect another couple hundred basis points of pressure on discounts and allowances with a typical seasonality in the first and fourth quarters.

Overall, we were very pleased with the performance of our MS business in 2018 and are focused on maintaining the resilience of this franchise in light of new competition entering the market. We expect the rate of change in full year global MS product revenues excluding OCREVUS to be similar in 2019 versus 2018, mostly offset by expected growth of OCREVUS royalties. Additionally, we expect a potential inventory draw down in the first quarter of 2019.

Let me now move on to SPINRAZA. Global fourth quarter SPINRAZA revenues were $470 million, a $30 million increase versus the prior year and relatively flat versus the third quarter. This included revenues of $236 million in U.S., an increase of 5% versus the third quarter and $234 million outside the U.S. a decrease of 4% versus Q3.

For the full year 2018, worldwide SPINRAZA revenues were nearly double to $1.7 billion. This included $854 million in the U.S. and $870 million in sales outside the U.S. The number of patients on therapy in U.S. increased by 9% as compared to the end of third quarter of 2018 and discontinuations remained relatively low.

In the U.S., we continue to make strong progress with adults. In the fourth quarter more than 50% of new starts were adults, increasing the total number of adult patients on SPINRAZA to nearly 1,000, an increase of approximately 20% versus the third quarter of 2018.

We saw a continued increase in the revenue contribution from maintenance doses this quarter. In the U.S., approximately 65% of SPINRAZA units in the fourth quarter were attributed to maintenance doses as compared approximately 60% in the third quarter.

In the fourth quarter, approximately 15% of U.S. SPINRAZA units were dispensed through our pre-drug program, similar to the third quarter and a decrease from approximately 20% a year ago.

Outside the U.S., the number of commercial SPINRAZA patients increased approximately 18% versus the prior quarter and there are approximately 260 patients active in the expanded access program.

We recorded revenue from over 40 international markets in the fourth quarter. Despite overall -- excuse me, despite strong overall patient growth, fourth quarter ex-U.S. SPINRAZA revenue increase slightly versus the third quarter due to combination of lower volumes in certain markets due to lowing dose dynamics, the timing of shipments in certain distributor markets, and pricing dynamics in certain markets.

In 2019, we expect global SPINRAZA revenues to grow in the mid to high-teens and we expect growth in both the U.S. and outside the U.S. We expect global SPINRAZA revenue to be relatively stable in Q1 2019 versus Q4 2018 due to seasonality followed by quarter-over-quarter growth.

Outside of the U.S., we expect continued patient growth in 2019, although at a slower pace in 2018. Overall, we were very pleased with both the performance and outlook for SPINRAZA as we continue to believe it has delivered the best launch from an orphan drug ever and continue to deliver strong growth for the company.

Let me now move to our biosimilars business, which generates $156 million revenue this quarter, an increase of 28% versus the prior year. Full year biosimilar revenues were $545 million, an increase of 44% versus the prior year.

BENEPALI continue to be the market leader in countries such as U.K., Denmark and Norway, and became the market leader in the Germany in the fourth quarter.

TYSABRI revenues grew 24% quarter-over-quarter. In October 17th, we launched IMRALDI, our biosimilar referencing HUMIRA. While it is too early to comment on specific share data, we can say that we are very pleased with IMRALDI sales performance in the first quarter in the market, in many cases surpassing the initial rate of uptake from BENEPALI

With the launch of IMRALDI, Biogen became the first company to offer all of the three main anti-TNF biosimilars across Europe. In 2019, we expect double-digit revenue growth from a biosimilars business, primarily driven by the launch of IMRALDI.

Turning to our anti-CD20 revenues, we recorded $535 million for the fourth quarter, an increase of 29% versus the prior year, primarily driven by OCREVUS royalties. Full year anti-CD20 revenues were $2 billion, a 27% increase versus 2017. Within anti-CD20 revenues our estimated OCREVUS royalties were $152 million for the fourth quarter and $478 million for the full year. We expect a slight decline in anti-CD20 revenue in 2019, driven by the expected launch of RITUXAN biosimilars in the second half of the year.

Total other revenues were $166 million in the fourth quarter, a decrease of 8% versus the prior year. Other revenues were $586 million for the full year, an increase of 63% versus 2017.

In 2019, we anticipate a modest increase in these revenues with revenue heavily loaded in the first quarter due to the affected timing of sales of approximately $200 million of remaining inventory associated with the Bioverativ’s spinoff, which carries a lower gross margin.

Let me now turn to gross margin performance. Q4 2018 gross margin was 86% of revenues versus approximately 86% in the fourth quarter of 2017, driven by unfavorable net mix of revenue in Q4 2017. Gross margins for the full year of 2018 were approximately 86%, relatively flat compared to the full year 2017.

In 2019, we expect gross margin compression due to sale of remaining Bioverativ inventory just discussed were substantially all the impact anticipated in the first quarter.

Q4 GAAP R&D expense was 17% of revenue or $612 million. Q4 non-GAAP R&D expense was also 17% of revenue or $602 million. Q4 R&D expense includes $35 million opt-in payment we made to Ionis related to BIIB067 for ALS and $17 million related to our collaboration agreement with C4 Therapeutics.

Full year GAAP R&D expense was 19% of revenue or $2.6 billion. Full year non-GAAP R&D expense was 18% of revenue or $2.4 billion. We expect Q1 2019 R&D expense to include approximately $35 million, related to our collaboration agreement with Skyhawk.

Q4 GAAP and non-GAAP SG&A were both 17% of revenue or $591 million. Full year GAAP and non-GAAP SG&A were both 16% of sales or $2.1 billion. Both GAAP and non-GAAP SG&A increase versus the prior quarter, due to the timing of spend as well as certain investments across sales and marketing, worldwide medical and G&A. In 2019, we expect total OpEx per quarter to be slightly above $1.1 billion, as we continue to invest in our pipeline and prepare for the potential launch of aducanumab.

GAAP other net expense which includes interest was $29 million in Q4 and GAAP other net income was $11 million for the full year. Non-GAAP other net expense was $16 million in Q4 and $117 million for the full year. We expect other net expense to be lower in 2019 due to higher interest income resulting from larger cash balances and higher interest rates versus 2018.

In Q4, our GAAP tax rate was approximately 33% as we booked a GAAP tax charge of $136 million related to the initial recognition of deferred taxes on the GILTI tax of international earnings, a component of U.S. corporate tax reform by this legislation.

In Q4, our non-GAAP tax rate was approximately 21%. For the full year, our GAAP tax rate was approximately 24% and our non-GAAP tax rate was roughly 21%. In 2019, we expect the underlying run rate for our tax rates to benefit by approximately 200 basis points as a result of U.S. corporate tax reform.

Our weighted average diluted share count was approximately $200 million for the fourth quarter and $205 million for the full year. We repurchased approximately 1.3 million shares in the fourth quarter at an average price of $311.24 for a total value of approximately $1.4 billion, which now brings us to our diluted earnings per share.

In the fourth quarter, we booked GAAP EPS of $4.73 compared to GAAP loss of $1.40 per share in the fourth quarter 2017 and non-GAAP earnings of $6.99 per share, a 33% increase versus the prior year. For the full year, GAAP EPS was $21.58, an 81% increase versus 2017 and non-GAAP EPS was $26.20, a 20% increase versus 2017.

As a reminder, fourth quarter and full year 2017 GAAP EPS was negatively impacted by $5.51 due to U.S. corporate tax reform. We generated approximately $1.9 billion in net cash flows from operations in the fourth quarter and approximately $6.2 billion for the full year. We ended the quarter with approximately $4.9 million in cash and marketable securities and $5.9 million in debt.

Let me now turn to our full year guidance for 2019. We expect revenues of approximately $13.6 billion to $13.8 billion assuming current foreign exchange rates. We anticipate gross margins of 85% to 86%, driven by the unfavorable mix issues I discussed earlier.

We anticipate R&D expense between 16% and 17% of revenue. Of note, guidance does not include any impact from potential acquisitions or large business development transactions as both are hard to predict. We expect SG&A expense to be approximately 16% to 17% of revenues, as we expect to begin meaningful investments in launch preparation activities for aducanumab.

We anticipate our GAAP tax rate for 2019 to be between 18.5% to 19.5% and our non-GAAP tax rate to be between 18% to 19%. We anticipate full year GAAP diluted EPS results of $26.65 to $27.65 representing growth of 23% to 28% and non-GAAP diluted EPS to be $28 to $29, representing growth of 7% to 11%. From a quarterly perspective, it's important to recognize that we had a large business development expense in Q2 2018 effecting the year-over-year comparison for Q2 2019.

I'll now turn the call back over to Michel for his closing comments.

[Michel Vounatsos, Chief Executive Officer]

Thank you, Jeff. We closed 2018 with strong commercial performance, double-digit earnings growth versus a year ago and strong execution of our strategy. We opened 2019 with the announcement of two business development deals. We have enhanced our neuroscience pipeline and broaden our capabilities across multiple modalities as we prepare for multiple upcoming important readouts.

Biogen's vision and strategy are clear. As a pioneer, we aim to capture the significant unmet medical need in neuroscience with a goal of bringing potential new therapies faster and more efficiently to patients. For 2019, we aim to continue our momentum and achieve our guidance.

To deliver on our aspirations, we remain focused on executing well on our strategic priorities to fortify our core business in MS and SMA. And also, allocate capital to expand and progress our neuroscience pipeline while opportunistically returning capital to shareholders.

Biogen will continue to actively pursue business development and M&A. Within the next 12 to 18 months, we expect further progress as we aim to build a multi-franchise neuroscience portfolio including data reduction Alzheimer's, including the final Phase 3 data for aducanumab as well as MS and PSP. Up to five new assets advancing into the clinic and potentially regulatory approval in the U.S. for VUMERITY in MS.

Finally, I want to reiterate our commitment to maximizing return to our shareholders and bringing innovative strategies to patients 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 return from the investment we make.

Once again, I would like to thank our employees around the world, who are dedicated to making a positive impact on patient’s life and all of the physician, caregivers and participants in our clinical development programs, our past and future achievements could not be realized without the passion and commitment.

With that, we will open the call for questions.

[Operator]

Certainly. [Operator Instructions] Your first question comes from the line of Geoff Meacham with Barclays. Your line is open.

[Geoff Meacham, Barclays]

Hey, guys good morning. Thanks a lot for the question. Michel, when I look at 2019 guidance, it reflects a slower growth profile for both revenue and earnings. So, the question is from a strategy perspective, does this alter your view on BD, your capital allocation, or do you look at 2019 growth as more of a temporary trend?

And then Mike or Al, real quick, I just wanted to ask you guys on the new Phase 3 study for aducanumab in earlier stage Alzheimer's. Was this informed at all from ENGAGE, EMERGE or PRIME or something else? Thanks.

[Michel Vounatsos, Chief Executive Officer]

Thanks for the good questions. So, the strategy as you know is clear and simple and very usable. There’s three main reasons to believe; first, we have a strong underlying momentum, solid base, value proposition, improving with the offer of biosimilars and we are working on the operating model.

Second, we have a strong and stronger engine for growth with all the enhanced pipeline that Mike spoke about, and we have very important landmark study readouts in the coming period, so this is a very exciting place to be.

Third, we have financial strengths. So concerning the BD and M&A, the drive first will be to continue to accelerate the buildup of our modalities and pipeline. This will be the key driver, scientific and strategic alignment.

We will not go for bridging a potential gap because we are not on a burning platform. The team is building up very well; the management team is spending a lot of time on those activities. We have a broad range of targets and we are working on that but with pace and calm.

[Al Sandrock, Chief Medical Officer]

So, hi Jeff, this is Al. On your second question, we've been considering doing this preclinical study, we call it, for a few years now and it's part of our broader life cycle management strategy.

I'd say the reasons why we're doing it are that many of our advisors and investigators have been encouraging us to do it for some time, and I would say also that the BAN2401 results that we got roughly six months ago increases our level of confidence in aducanumab, and then finally as you know FDA put out guidance recently that contemplates how you might get approval for early AD. So we believe one day, the standard of care will be to treat with amyloid-lowering drugs as early as possible and this trial will go a long way toward informing that.

[Operator]

Your next question comes from the line of Michael Yee with Jefferies. Your line is open.

[Michael Yee, Jefferies]

Thanks, good morning. Congrats on the good quarter. I know everyone is focused on interim analysis, so I’m asking if there will be an interim analysis on aducanumab? Just asking actually, it feels like the street would like to know if you had one or if you had a futility analysis whether that would be disclosable if you passed either of those?

I think Roche talks about the futility and how that's a material piece of information, so I just wanted to understand your view on whether you took either of those of if they will be on futility and whether that’s disclosable? Thanks so much.

[Al Sandrock, Chief Medical Officer]

Mike, this is Al. I am really sorry, but we continue to have a policy here that we don't talk about interim analysis.

[Operator]

Your next question comes from the line of Terence Flynn with Goldman Sachs. Your line is open.

[Terence Flynn, Goldman Sachs]

Hi. Thanks for taking the question. With respect to SPINRAZA ex-U.S, I was just wondering if you can give us a little bit more detail on the impact in the fourth quarter from pricing versus loading dose, and then maybe help us think about the pacing going into 2019? And ex-U.S. reimbursement progress, any new countries that you guys are expecting to come on board in 2019? Thanks.

[Michael Ehlers]

Thanks for the question. So just to reiterate, we're very pleased with the performance of SPINRAZA, both in the U.S. and outside the U.S. and think it has a very strong growth profile. It was up 60% year-over-year although down a little bit sequentially.

As I mentioned, really there are three factors that drove the sequential decline and that was; one, a shift from loading to maintenance doses in some of the more mature markets in Europe, the timing of shipments in certain distributor markets which are hard to predict, and then pricing dynamics including unfavorable country mix.

So as we look forward in 2019, we expect for that franchise to resume growth. We expect that to come from several sources. Number one, in the mature markets, just like we saw the dynamic of the shift in the U.S., we expect some of these larger markets to return to growth in 2019. Second, although the IPM, or International Partner Markets, will continue to be lumpy, they are a good source of growth for us, so we expect that to grow as well.

And then if you look at new markets, either entry into new markets for expansion into markets that we've just recently entered, there's a number of kind of interesting things that are happening. If we look at Europe first, we expect to enter the U.K. at some point in 2019 which would be a good size opportunity. In Turkey, we've been very successful in Type 1. We expect to kind of get Type 2 and Type 3. Saudi Arabia, Poland, and Portugal are all markets we expect to enter as well from a European perspective.

Moving around the world, Canada, we just recently got approval in the fourth quarter of 2018. We expect that to be a good growth opportunity for us and a good market. And then, if you look across the rest of the world, in Asia Pacific, South Korea, we expect to get reimbursement in that market in 2019. Taiwan is another good sized market, Hong Kong. And then, in China we expect to get in on a self-pay basis.

And then, Latin America, Brazil could be a sizable country. Today it's on a one-off approval basis. We expect to get reimbursement from the epidemiology is in the thousands in Brazil. So there's ample opportunity for us to grow. It's diversified regionally and by country. That's a real testament to both the effectiveness and reception of SPINRAZA worldwide.

[Michel Vounatsos, Chief Executive Officer]

So we expect to grow SPINRAZA during 2019 in the U.S. and ex-U.S. Remember, in the U. S. one year ago we're not sure by the ability of the organization to penetrate the large adult segment of the prevalence and we add 15%. This has driven more than 50% of the new starts in Q4. There is still a very long way to go. The organization is ready, working on that and beyond the U.S. just give some color.

[Operator]

Your next question comes from the line of Geoffrey Porges with SVB Leerink. Your line is open.

[Geoffrey Porges, SVB Leerink]

Thank you very much and I appreciate all the information on the call. I had a question on BIIB067. Mike, could you talk a little bit about the data? When we might see it? Whether you've had a chance to discuss it with the FDA? The size of the cohort? And how quickly this could advance? You seem quite excited about the signal. And then, perhaps you could just address what the general principles you take away from this finding are for the rest of your program? Thanks.

[Michael Ehlers]

Yes. Thanks, Geoff, for the question. A few things, hopefully I'll touch on each of these points. We will plan to present the data at an upcoming scientific meeting. We haven't quite yet determined that, but that will be in the coming months where we'll be able to talk about it some length.

We wouldn't really comment on our regulatory strategy at this point, I guess, what I would say is that we know this is a very severe disease. It's really little to nothing for these patients. So our anticipation here is that there would be good receptivity for the kind of efficacy that we think that we can see here.

Just on the data itself, so this is a Phase I study, keep in mind it was designed to be a safety study as primary endpoint of this patients largely, but we incorporated a number of biomarker pharmacodynamic and clinical endpoints in this.

And as I describe, it has been the collection of these both the lowering of SOD1 and the CSF has statistically significant a trend towards lowering in CSF neurofilament as well as three separate clinical outcomes, the ALSFRS, the slow vital capacity for respiratory function, the handheld dynamometry for muscle strength, and the concordance between these endpoints that have led to our excitement for these program.

And I would say the general takeaways you're asking about it’s really two dimensions. One, is this is very, very encouraging to us across our ASO platform, I would say. This is our second foray after SPINRAZA. We've got many other clinical programs, new molecule as we get to the clinic. It shows us that in adult onset neurological disease we're targeting an RNase H-dependent mechanism that we are seeing signs of clinical efficacy.

I believe it will be the first demonstration of proof-of-clinical concept in adults with an RNase H mechanism per se. So we're excited about that. That's one dimension. The other is that the promise that this holds broadly speaking for us in ALS, and neuromuscular disease in general.

[Operator]

Your next question comes from the line of Cory Kasimov with JPMorgan. Your line is open.

[Cory Kasimov, JPMorgan]

Great, good morning. Thanks for taking my question. So, Al, I know you won't comment on any potential internal interim analysis. But I'm curious to get your thoughts around the expected upcoming interim readout for Roche’s crenezumab in Alzheimer's, and so far as what you see as some of the kind of the key similarities and differences between your drug and Roche’s drug? And also whether you see much of a read through to aducanumab based on these pending results?

[Al Sandrock, Chief Medical Officer]

Hi, Cory. I be cautious about too much read through. First of all these are not the same antibodies, crenezumab binds to sort of a mid-domain in A-beta42 peptide, aducanumab and BAN both are in terminal.

Aducanumab and BAN are highly selective for aggregated forms of A-beta both soluble oligomers as well as insoluble fibrils, crenezumab doesn't have that same level of specificity. I think it's important to note that crenezumab is an IgG4, which doesn't have full effect or function, whereas, BAN and adu both have full effect or function.

And finally, we just saw the results published recently on crenezumab Phase 2 where even their high dose IV arm, they did not show statistically significant lowering of amyloid plaque whether you use subcortical white matter or cerebellum as a reference region.

So that's another important difference between aducanumab and BAN, both of which show substantial reduction in amyloid plaque burden in human. So I think there are some notable differences, and I'll be cautious about too much of a read through.

[Operator]

Your next question comes from the line of Chris Raymond with Piper Jaffray. Your line is open.

[Chris Raymond, Piper Jaffray]

Hey, thanks. Just a couple of financial questions. Just on the tax guidance, I think you're guiding to 200 to 300 bps lower year-on-year, and I know you cited corporate tax reform as the driver. But can you just maybe talk about the step down from 2018 or even the Q4 rate, which presumably should have benefited in tax reform? And is that number sustainable beyond 2019?

And then just on the inventory, I think last year you guys had $50 million Q4 inventory build for the MS franchise. This year I think it looks like it more than double, can talk about what's driving that difference? Thanks.

[Jeff Capello, Chief Financial Officer]

Yeah, so on the tax rate, if you back up to 2017, when we -- when U.S. tax reform got passed, we dropped the tax rate about 300 basis points and at that point we said that there was a further reduction in the tax rate due to tax reform that because of the way our legal structure works from an international perspective, there was inventory that would turn to the system and that would be for the reduction of the race.

So that 200 basis points is really kind of the higher simplistically think about is higher priced inventory from a tax perspective return to the system in 2018. So now in 2019 that inventory is gone, another raise is dropped. So I'm not able to kind of give you a long-term tax rate at this point.

We don't know long-term guidance, but we're comfortable with the rate going down 200 basis points from 2018 to 2019. And then thereafter, it will depend on a lot of things including the distribution of earnings and other things. But for now, I think, the guidance for 2019 is something you can rely on.

With regard to inventory, yes, so we built about $115 million worth of inventory in the fourth quarter compared to a build of roughly $50 million in the fourth quarter of last year, a lot of that’s outside our control. We distribute our product through distributors and they decide to either build inventory or not and we'd recognize revenue on shipment into the channel, which is different than kind of the flow through or consumption of that inventory, which is what we highlighted for people so they can normalize.

So it's just beyond our control. It's not something that we have control over. So it's driven by external factors and we do our best to kind of manage through those and make sure it's clear to people in terms of what's driving demand.

[Operator]

Your next question comes from the line of Umer Raffat with Evercore. Your line is open.

[Umer Raffat, Evercore]

Hi, guys. Thanks for taking my questions. First on aducanumab. My question is, and I have fully acknowledged and I don't think I ever asked about that interim. But my question is this. I realized there's a policy of not commenting on it, but once you do get a notification from the DSMB, given the sheer materiality of this, will you not put out a statement? And I guess that's really what I'm trying to get at, like, for example, trials continues as planned, like, will that happen or not happen once there is a notification to the management?

And then Jeff, on inventory my question is, so the Q4 – the inventory we saw on the slide and the disclosure for last year is obviously different than the inventory numbers that were reported last year, because of the change you guys implemented in 2Q. But my question is, in 2Q that inventory slide has two different metrics and it's been a little confusing to figure out when we see the inventory disclosures now, which of those metrics are actually being reported because the numbers are different on both.

[Alfred Sandrock]

Umer, this is Al, I am sorry, but we just can’t comment on interim analysis.

[Michael Ehlers]

With regard to inventory, Umer, what we disclosed is the change within the quarter, for the beginning of the quarter to the end of the quarter, that's a number of thing we have consistently disclosed in the press releases so that is generally inventory build up by $115 million from the beginning of the fourth quarter to the end of the fourth quarter of 2018. Similarly in 2017 from the beginning of the fourth quarter of 2017 to the end, it's built by $50 million. So the change within the quarter is up $115 million in the fourth quarter of 2018 and up $50 million in the fourth quarter of 2017. So we think the relevant metric people should look at is what was the change within the quarter and if you want to know what the change was comparatively, you take the difference of the change in the change, which is $65 million I think that's pretty clear.

[Operator]

Your next question comes from the line of Matthew Harrison with Morgan Stanley. Your line is open.

[Matthew Harrison, Morgan Stanley]

Great. Good morning. Thanks for taking the question. I just want to clarify some comments you made about rebates and your outlook on the MS business, broadly can you just speak in a little bit more detail kind of like you were expecting a few hundred basis points of additional chargeback rebate pressure this year in the U.S. You thought that would be offset by OCREVUS, maybe you could just comment broadly on your outlook for the MS business in the U.S. and outside the U.S.? Thanks.

[Michael Ehlers]

So I think you're referring to two different things. I think we said we expect that our discount and allowances in the U.S. take to offer another couple hundred basis points which is very similar to what happened in 2018. And that's been driven by the mix of the business becoming more Medicaid, Medicare and 340B Hospital reliant in terms of the channel it goes through where there is higher discounts. So no different than the trend we saw from 2017 to 2018. We'll see more pressure from 2018 to 2019.

With regard to the performance of the MS business, I think we said that we expect that business globally to perform similarly excluding OCREVUS to what it did in 2018. And then for any difference would be made out by the OCREVUS royalties and the combination of both of those to be resilient which we kind of, say, flattish. So we expect the kind of the trends with regard to improvement to continue in the U.S., which is very encouraging and the outside the U.S. we will continue to see some pricing pressure and competition with OCREVUS rolling through Europe.

[Operator]

Your next question comes from the line of Ying Huang with Bank of America-Merrill Lynch. Your line is open.

[Ying Huang, Bank of America-Merrill Lynch]

Hi. Good morning. Thanks for taking my questions. A quick one for maybe Al. We know that cladribine is being in the registration with FDA. I was wondering do have any thoughts on cladribine impact on the MS market? Could we see something like OCREVUS in the U.S. dynamics?

And then secondly on SPINRAZA, from last quarter to this quarter your market share in infants and also in pediatrics have been stable about 50%. Do you see further growth in those two segments for SPINRAZA in the U.S. this year? Thank you.

[Al Sandrock, Chief Medical Officer]

Hi, Ying. This is Al. On cladribine it’s -- we welcome any new therapy for MS patients, that's good for patients and good for doctors to have multiple options for their patients because MS patients are different, every one of them.

Having said that cladribine, it's oral, it's very convenient in the sense that you can give it every six months essentially a cycle every six months if you will, and the key question early on was the safety, which in some of the Phase III data there were some signals that were concerning, which prevented it from being approved a few years ago, and some of those questions may still remain, which takes sort of -- which makes the convenience of it less optimal if you will. So I'll just stop there.

[Michel Vounatsos, Chief Executive Officer]

Concerning SPINRAZA in the U.S. for infants and children if it was your question, we do believe that it is still opportunity to improve the penetration. The reason why we are 50% for infants is that some are still too advanced, and therefore they cannot be dosed.

For children and toddlers, one of the challenge was the complex spine, and we can see that the clinicians are able to dose better nowadays that they have more experience. So, we should be able to continue to make reasonable inroads. The biggest potential again remains really adult, the 60% opportunity for, which we penetrated thoroughly 15% and now have the capability, the reach and the infrastructure in terms of dosing capability and coverage is establishing the U.S.

[Al Sandrock, Chief Medical Officer]

Just as a reminder, we've got 2,600 patients in therapy in U.S. today; we estimate the total potential is 9,000. There's a lot of room to grow from perspective interest.

[Operator]

Your next question comes from the line of Alethia Young with Cantor Fitzgerald. Your line is open.

[Alethia Young, Cantor Fitzgerald]

Hey, guys thanks for taking my question. Congrats on the progress. I guess, I want to talk a little bit more about, what you think have been impactful in your efforts with adult, SMA, and I’ve seen that you're making some progress there. So, just wanted to get some more color on that? Thank you.

[Michel Vounatsos, Chief Executive Officer]

I would like to say that it starts with the team and the capability that Biogen was able to deploy in the marketplace. It takes a little bit of time for the more urgent infant population, for which we new that was a natural history the outcome of it, and the treatment centers were well identified.

For the adult population, less symptomatic that can live with some symptoms but they can live quite long life. It was a bit more difficult and challenging to find treating centers and to mobilize them for a better quality of life.

So this is why it took a little bit more time. So we enlarge the team, we did a lot of work in terms of medical affairs, and finally we showed that for the adult population there were incremental gains in functionality and this played a very important role. Al you want to add?

[Al Sandrock, Chief Medical Officer]

Yeah, I mean, many of these patients weren't seeing a neurologist anymore. They were maybe seeing rehab specialists, but they had -- since there was no treatment, they really weren't seeing neurologist even neuromuscular neurologist weren't really seeing them.

But now that there is a treatment, they're starting to find doctors and the doctors -- and it turns out their neuromuscular doctors are the same ones that are treating ALS patients by the way that are now treating a SPINRAZA patients that plus the fact that interventional radiologists have gotten really good at finding ways to get into this -- into the intrathecal space when people with complex spine, spinal fusions and other things present, and so I think it's a combination of both.

[Operator]

Your final question comes from the line of Robyn Karnauskas with Citi. Your line is open.

[Robyn Karnauskas, Citi]

Hi, guys. Thank you for taking my question. So, because AveXis will be launching in kids, sometime people believe early for -- some time in middle of the year, in the first half of 2019, how do you view that uptake?

And do you think it's – you mentioned that some of these babies have difficulty getting the intrathecal infusions, would you think that be the area in which they'd start to take share? Or do you still believe that AVONE most likely will get a combination approach of gene therapy and SPINRAZA?

I'm just trying to get a sense of when we start to see that impact, how are you thinking about that for 2019 in your guidance? And then second question was, just on the inventory draw down, so do we still expect to have all of that inventory be taken out in the first quarter? Or do you think there'll be a higher level of inventory laying around for the year? Thanks.

[Michael Ehlers]

Okay. Robyn, this is Mike. I'll start on this and turn it over. I think our assumptions around the Novartis AVXS-101 gene therapy launch is, they've disclosed they filed in the U.S., E.U. and Japan for Type 1. Our base case is that they launch in the middle of the year and we expect that their initial label to be for Type 1 patients and mainly infants. And of course, we've been talking about it in the call, the majority of patient in Type 2 increase. So we really see this as probably being positioned for the Type 1 or the infantile SMA.

Then I think the latter part of your first question was that we do think that there is opportunity for complementarity between modalities. The NURTURE data in our mind with SPINRAZA demonstrates a nearly maximal potential efficacy in terms of normal motor development if you treat in that first six-week period with SPINRAZA.

That really I think sets the bar for the standard-of-care and it highlights the fact that at some level you really can't mess around on this. You've got a time window where maximal SMA protein expression really matters and I'd say the data that we’ve generated with SPINRAZA really sets the bar very high.

[Al Sandrock, Chief Medical Officer]

And the with regard to your question on inventory, we would expect the vast majority of the $200 million worth of inventory would get sold through in the first quarter and then there would be none left. Although, we need to manufacturing with Bioverativ but that's completely separate – distinct from the legacy inventory.

[Michel Vounatsos, Chief Executive Officer]

So for 2019 we aim to continue our momentum while we are getting ready for very important readouts. Thank you all for joining us today on our call.

[Operator]

This concludes the Biogen Fourth Quarter and Full Year 2018 Financial Results and Business Update Call. We thank you for your participation. You may now disconnect.