Good morning. My name is Carmen, 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 2019 Financial Results and Business Update. All lines Please be Thank you. I would now like to turn the conference over to Mr.
Joe Mara Vice President, Investor Relations. You may begin.
Good morning, and welcome to Biogen's 4th quarter 2019 earnings call. Before we begin, I encourage everyone to go to the Investors section of the Biogen dot 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 12 and 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've also posted our 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 in 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, Michelle Vanazzos, Doctor.
Al Sandrock, EVP Research And Development and our CFO, Jeff Capello. Now, I will turn the call over to Michel.
Good morning, everyone, and thank you for joining us. First, let me start with some financial highlights. Biogen closed 2019 with quarterly revenues of $3,700,000,000, an increase of 4% compared to the same period a year ago. For the full year 2019, Biogen generated $14,400,000,000 in revenues, representing growth of 7% year over year. Full year 2019 GAAP earnings were $31.42 a share, a 46% increase versus full year 2018.
Full year 2019 non GAAP earnings were $33.57 a share, a 28% increase versus full year 2018. We are pleased with the strong year over year growth as we continue to execute on our strategy for long term leadership in neuroscience. Now let me review the $1,000,000,000, an increase of 2% versus the prior year. The number of patients on our MS products globally increased 3% versus the prior year, driven by strong patients growth in emerging markets as well as all of the large mature European markets and our business demonstrated resilience in the U S. Our team has executed well, demonstrating our ability to compete in an increasingly crowded market.
We launched VUMERITY in the U. S. As an important neural treatment option. It remains early in the launch, but so far, we are pleased with the level of interest from patients and physicians. 2nd, SPINRAZA generated full year global revenues of $2,100,000,000, a 22% increase versus the prior year.
This blockbuster performance was driven by strong year over year expanded access program and clinical trials over 10,000 patients are now being treated with SPINRAZA. 3rd, Full year biosimilars revenue were $738,000,000, which represents 35% growth year over year, driven primarily by Imhaldi. We estimate that our biosimilars generated approximately 1,000,000,000 of savings to the European Healthcare Systems in 2019. Which we expect will continue to increase in 2020. This is critical as we work to create financial headroom for innovation and contribute to the long term sustainability with a new transaction with Samsung BioAPIS.
This provides us access to 2 new potential biosimilars in ophthalmology with a significant market opportunity in major markets worldwide, including for the first time in the U. S, as well as commercialization rights, to our anti TNF biosimilars in China. 4th, this was an historic year for R&D Organization, we are inspired by what the positive implications of the aducanumab data may mean for patients, physician and the broader scientific community have been waiting decades for therapy that can reduce the clinical decline of Alzheimer's disease. We are actively engaging with the FDA well as regulators in Europe and Japan, and we look forward to completing regulatory filing in the U. S.
As soon as possible. In addition, There has been important progress related to the redosing study as we have successfully submitted the protocol to the FDA, and we are currently working with the sites and ASIC committees towards study initiation. 5th beyond aducanumab, we continue to expand and progress our pipeline with approval for VUMERITY in the U. S, a positive data readouts for BIIB059 and adding 7 new clinical programs in MS, ALS, Parkinson's disease of thalmorology and brain confusion. 2019 was one of our most productive years in R&D, and we believe we have multiple opportunities for near term value creation as we prepare for multiple potential launches in the early 2020 6, our cash flow generation remains strong and continue to provide us with significant optionality and flexibility to allocate capital.
In 20 we generated approximately $7,100,000,000 in cash flow from operations, an increase of approximately 14% versus the prior year. Throughout the year, we repurchased approximately 24,000,000 shares for a total value of approximately $5,900,000,000. As we have stated previously, we do share repurchase as an important element of thoughtful and value creating the financial flexibility and capacity to continue to evaluate potential external business development M and A opportunities. Over the past 3 years, we have executed 15 business development transaction, which have contributed to the significant expansion of our pipeline. We executed 4 deals over the past 3 months alone, including our proposed transaction with Pfizer for a potential symptomatic therapy with potential application in both Alzheimer's disease and Parkinson's disease.
As we have demonstrated in the past, we are committed to maximizing return to our shareholders, while continuing to bring innovative therapies to patients something that demands a thoughtful approach towards all our investment over both the short and the long term. In summary, 2019 was a very productive and successful year for Biogen as we executed on our strategy and continued to deliver noticeable progress. Our core MS business continued to demonstrate resilience with growth in both patients and revenues, and we are excited to be launching VUMERITY. SPINRAZA continued to grow in the U. S.
And even more so outside of the U. S. As we continue to expand into new geographies. With over 10,000 patients on therapy and the largest body of clinical data in SMA, SPINRAZA remains a foundation of care in SMA. We grew our biosimilars business and we expanded our portfolio and geographic presence.
We are preparing to lead in the fight against Alzheimer's disease as we plan for a U. S. Fighting for aducanumab. Beyond aducanumab, we expanded and progressed our pipeline with 7 new clinical programs and the positive data readouts in lupus. And we generated ample cash flow as we focused on strategically allocating capital to maximize shareholder return over the long term.
I will now turn the call over to Al for a more detailed update on our recent progress in R&D.
Thank you, Michelle, and good morning, everyone. Before I begin, I would like to welcome back Doctor. Maha Radna Krishnan as the new Chief Medical Officer at Biogen. Maha brings more than 16 years of experience across multiple geographies in a broad range of therapeutic areas, She previously worked with us here at Biogen as Vice President, Europe And Canada Medical And Vice President U. S.
Medical and subsequently held senior positions in medical affairs at Bioverativ and Sanofi. Maha's extensive background will be crucial as we prepare for future pipeline launches, including the potential launch of aducanumab. As Michelle discussed, 2019 was an historic year for Biogen. In addition to announcing positive results on aducanumab, we made significant progress on building a multi franchise portfolio by receiving approval for pumority, adding 7 clinical programs and advancing 2 programs to phase 3, reflecting our modality agnostic approach Our neuroscience pipeline now includes small molecules, antibodies, other advanced biologics, antisense oligonucleotides and gene therapy. Let me now turn to the advances we made in the fourth quarter starting with Alzheimer's disease and dementia.
At the clinical trials on Alzheimer's disease, or CTAD annual meeting held last month in San Diego. We presented top line results from the phase 3 studies of aducanumab in early Alzheimer's disease. Final analysis of these data showed that IMerge was a positive on both the pre specified primary endpoint of CDR Summit boxes, as well as on all three pre specified secondary endpoints. On the other hand, data from to high dose aducanumab and engage support the findings of IMerge. Please note that we do not expect to present additional data on aducanumab prior to FDA, we are working to initiate the open label aducanumab redosing study as soon as possible.
We have successfully submitted the protocol to the FDA, and we are currently working previously enrolled in our clinical studies, including patients previously treated with either aducanumab or placebo will be titrated to 10 milligrams per kilogram aducanumab infusions every 4 weeks. In addition to aducanumab, we continue to advance a broad Alzheimer's disease portfolio, including the phase 3 study of BAN2401. BIIB080 at tau targeted anti solicunucleotide in phase 1, BIIB076 and anti tau antibody in phase 1, and Gosuranumab a distinct anti tau antibody in phase 2 for which we expect data next year. As we continue to develop our Alzheimer's portfolio, we aim to expand into even earlier patient populations to potentially prevent the clinical onset our collaboration partner Eisai, along with the Alzheimer's clinical trials consortium, plans to initiate the AHEAD-three forty five program. AHEAD-three forty five is comprised of 2 studies termed A3 and A45.
The A3 study will evaluate low dose BAN2401 versus Placebo and cognitively normal individuals who are currently below the threshold for amyloid positivity but are at high risk for further amyloid accumulation. The A45 study will evaluate high dose BAN2401 versus placebo. In individuals who are amyloid positive, but show little to no cognitive impairment. Together, these studies will evaluate whether it administration of BAN2401 can slow amyloid accumulation or cognitive decline in the very early stages of Alzheimer's disease. Turning to MS and neuroimmunology.
This quarter, we were pleased to announce that Vumerity, a novel oral fumarate, was a approved by the FDA for the treatment of relapsing forms of MS. Detailed results from the phase 2 EVOLVE MS2 study which directly compared and published in the journal CNS Drugs earlier this month. Specifically, on the primary endpoint, These data showed that patients treated with Verity self reported 46% fewer days with intensity scores of at least 2 on the individual gastrointestinal symptom and impact scale compared significant with a P value of 0.0003. Consistent with these data, the proportion of patients who discontinued the study due to GI adverse events was 0.8% for VUMERITY and 4.8% for TECFIDERA. Together, these data indicate that VUMERITY offers a clinically meaningful improvement in GI tolerability compared with DECFIDERA.
Across our MS portfolio, we continue to advance BIIB-ninety one and oral BTK inhibitor in phase 1, BIIB-sixty one an oral remyelinating agent in phase 1 and opicinimab, a phase 2 anti lingo antibody for which we expect data in people living with lupus, including both cutaneous and systemic forms. Treatment options for lupus are limited and new medicines are needed to manage builds on a long history that Biogen has in immunology, including both homegrown assets and collaborations We were very excited to report positive data this quarter from the phase 2 lilac study of BIIB59. A potential 1st in class antibody approximately 800,000 individuals in the G7. This 2 part study evaluated BIIB059 versus Placebo and individuals with active cutaneous lupus erythematosus or CLE with or without systemic manifestations, and in individuals with systemic lupus erythematosus or SLE with active joint and skin manifestation with a P value of less than 0.001, the CLE part of the study met its primary endpoint by demonstrating a statistically significant response of 559 on the percentage change from baseline in the Cloughesy A Score at week 16. The SLE part of the study also met its primary endpoint of reducing disease activity as measured by chain from baseline in the total number of tender or swollen joints at week 24.
In this study, patients treated with 450 milligrams of 9 experienced a statistically significant reduction of 3.4 total active joint counts compared to Placebo. In addition, improvements in skin disease and overall disease activity were consistently observed across multiple secondary endpoints. The safety and tolerability of BIIB059 59 supports this continued development, and we are planning to move forward to phase 3. We believe that the BIIB059 program exemplifies important elements of our broader approach to R and D at Biogen. For example, by implementing biomarkers of target engagement and a measure of clinical efficacy early in clinical development, we were able to generate compelling proof which were subsequently confirmed in a well controlled phase 2 study.
We believe that such de risking strategies may serve to increase the probability of success of other programs across Last month at the International Symposium on ALS motor neuron disease, Biogen, Ionis, Pharmaceuticals, and our collaborators were awarded at Massachusetts General Hospital. This award recognized our contributions to the discovery and development of Dofersen, our antisense oligonucleotide for SOD1 ALS. At this meeting, we were pleased to present the final data from the Phase III study of Tafersen, which demonstrated a statistically significant decrease in CSF SOD1 protein levels and trends towards slowing to first and reduce levels of neurofilament in both plasma and CSF. We are encouraged by the concordance across data generated in the study, including target engagement, clinical and neurofilament data, and the broad potential of antisense oligonucleotide to target genetic drivers of neurodegenerative disease. We expect data from the phase 3 valor study of Tuherstin next year.
In addition, we continue to advance the phase 1 studies of BIIB078 and ASO for C9orf72 mediated ALS and BID100, a small molecule inhibitor of XP01 for sporadic ALS. Turning to ophthalmology. This quarter, we completed enrollment in the phase 3 STAR study of BIIB-one hundred and eleven in choroideremia. A rare X linked inherited retinal disorder that inevitably leads to blindness and currently has no approved treatments. Coroideremia affects approximately 15,000 individuals in the G7 and is caused by loss of function mutations in the gene encoding RAB S Corp protein 1 or REP-one hundred and eleven is a gene therapy aimed to address the underlying cause of this disease by expressing a higher rate of maintained vision compared to natural history.
In addition, a subset of patients treated with BIV-one hundred and eleven in phase 1two studies demonstrated a meaningful improvement in visual activity as defined sorry, in visual acuity as defined by a gain of at least 15 letters corresponding to 3 lines on the eye chart. Specifically, 21% of patients treated with BIV-one hundred and eleven demonstrated an improvement of at least The Phase III studies also demonstrated that BIV-one hundred and eleven was generally well tolerated profile. We are encouraged by these early signs of efficacy and safety and look forward to data from the phase 3 study of BID-one hundred and eleven toward year. In stroke, we continued to advance the Phase 3 study of BIIB093 or IVglobanklamide for cerebral edema caused by large hemispheric infarction or LHI. In a Phase 2 study, treatment with BIIB093 was associated with 46% reduction in mid line shift, an imaging measure of cerebral edema and reduced mortality by over 50%.
We look forward to In addition, the phase 2 study of TMS-seven continues to progress. TMS-seven is a small molecule modulator of plasminogen that has the potential to become a best in class thrombolytic drug candidate for patients following an acute ischemic stroke. Data from this study are expected by the end of this year. Within movement disorders, we continue to advance synpanaumab or BIIH54, an anti alpha synuclein antibody for Parkinson's disease, with phase 2 data expected in the second half of this year, as well as the phase 1 study for BIIB094 and antisense oligonucleotide targeting LORC2. Last month, we reported top line results from the phase 2 Passport study of Gosuranumab for PSP.
The primary endpoint was not met and we therefore discontinued the development of Gosiranumab for PSP and other primary tauopathies. While we were disappointed in this result, we chose to continue the phase 2 study of Gosuranumab in early Alzheimer's disease given the potentially significant differences in disease pathophysiology. In neurocognitive disorders, we continued to advance a Phase 2 study of BIV-one hundred and four, an AMPA receptor potentiator for cognitive impairment associated with schizophrenia. We now expect data from this study in the second half of this year of next year. Finally, we had a productive quarter on the business development front.
Building further depth in ophthalmology, last month, we entered into an agreement with Catalyst Biosciences, to develop and commercialize pegylated CV2782 for the potential treatment of geographic atrophy or GA. GA is an advanced form of dry age related macular degeneration or AMD that leads to blindness, has no approved therapies, and affects approximately a million individuals in the U. S. Alone. This molecule is a novel protease that selectively cleaves C3.
A genetically validated target in AMD, and we are encouraged by preclinical data demonstrating that a single intravitreal injection of this protease eliminated over 99% of C3 from the vitreous humor for at least 28 days. In addition, this quarter, we initiated collaboration with Camp IV Therapeutics to leverage their gene circuitry platform to potentially identify a suite of druggable targets in microglial signaling pathways already known to play a causal role in neurological disease. And most recently, we announced an agreement to acquire a novel CNS penetrant small molecule inhibitor of pacine kinase 1, or CK1 from Pfizer. CK1 is a key regulator of circadian rhythms, which can become disregulated and contribute to irregular sleep wake rhythm disorder or ISWRD in Parkinson's disease, as well as sound downing in Alzheimer's disease. ISWRD is a non motor symptom of Parkinson's disease characterized by fragmented sleep, severe fatigue and difficulties with activities of daily living.
SUNDounding affects approximately 20% of AD patients and causes patients to become confused anxious and agitated later in the day. In a phase 1 study, phase 1a study, this molecule demonstrated an acceptable safety profile and proof on in concentration, a marker of circadian phase modulation. We believe this may represent an innovative symptomatic treatment for both AD and PD is subject to customary closing conditions and we expect it to close in the first quarter of 2020. Overall, Biogen R and D delivered significant progress in 2019. We believe we are in a strong position today with 27 clinical programs including 6 programs in Phase 3, 12 in phase 2 and 9 in phase 1, with a deep preclinical pipeline across multiple modalities.
With our plan to file aducanumab in the U. S. And multiple additional near term opportunities opportunities ahead of us, We believe that no other company is as well positioned to develop potentially breakthrough medicine for patients living with devastating neurological diseases I'll now pass the call over to Jeff.
Thanks, Al. Good morning, everyone. Let me now provide more detail on our financial performance for 2019. And share with you our guidance for 2020. Across all of our core business areas.
Total revenues for and grew 7% for the full year to $14,400,000,000. Overall, our MS business delivered revenues of $2,400,000,000 in the fourth quarter of 2019 including OCREVUS royalties of approximately $205,000,000. MS revenues in Q4 2019 decreased 1% versus prior year without OCREVUS royalties and increased 2% including OCREVUS royalties. U. S.
MS revenues in the fourth quarter of 2019 benefited from an increase in channel inventory of approximately $135,000,000 compared to an increase of approximately 105,000,000 in Q4 twenty eighteen. Based on historical results, we typically see a decrease in channel inventory in the first quarter following a year end build of inventory. Full year MS revenues were $9,200,000,000, including OCREVUS royalties of approximately 688,000,000 Full year MS revenues decreased 1% versus the prior year without OCREVUS royalties and increased 2% versus the prior year, including OCREVUS Royalty Global 4th quarter TECFIDERA revenues were $1,200,000,000, a 5% increase versus the prior year. This included revenues of $877,000,000 in the U. S, an increase of 2% versus Q4, twenty eighteen and $284,000,000 outside the U.
S. An increase of 12% versus the fourth quarter of 2018. Tecfider benefited from an increase in channel inventory in the U. S. Of approximately $100,000,000 in fourth quarter of 2019 compared to an increase of approximately $60,000,000 in Q4 2018.
Throughout 2019, we were pleased to 4 consecutive quarters, a relative stability in our share of total prescriptions for TECFIDER in the U. S. In addition to strong performance from TEC Bedera, we launched VUMERITY in late Q4 in the U. S. And recorded $5,000,000 of revenue, all of which we attribute to channel loading, Outside the U.
S, TECWIDER again performed very well in the fourth quarter with strong patient growth in all major European markets and approximately 50% patient growth in Asia Pacific And Latin America versus the prior year. For the full year, Worldwide Tecadero revenues were $4,400,000,000, an increase of 4% versus the prior year. This included $3,300,000,000 in the U. S. And $1,100,000,000 were $516,000,000 during the 4th quarter, a decrease of 14% versus Q4 2018 due to a continued shift from the injectable platforms to oral or high efficacy therapies.
This included $359,000,000 in the U S and $157,000,000 in sales outside the U S. Interferon revenues outside the U. S. Were negatively impacted by channel dynamics and timing of shipments. Within the U.
S, Avanix and Plagrady benefited from an increase in channel inventory of approximately $30,000,000 compared to an increase of approximately 35,000,000 q44 2018. For the full year, worldwide interferon revenues decreased 11 percent to $2,100,000,000, consisting of $1,400,000,000 in the U. S. And $675,000,000 in sales outside the U. S.
Tysabri worldwide revenues were $473,000,000 this quarter, an increase of 2% versus the fourth quarter of 2018. This included $270,000,000 in the U S and $203,000,000 outside the U S. In the U. S, revenues increased 5% versus the prior year, representing the 4th consecutive quarter of improved performance on a year over year basis. Within the U.
S, inventory levels for Tysabri were relatively stable compared to an increase of approximately $10,000,000 in the fourth quarter of 2018. Throughout 2019, we were pleased to see relative stability and Tysabri share of both new and total prescriptions in the U. S. Outside the U. S, Tysabri revenues decreased 2% versus the prior year as revenues were negatively impacted by channel dynamics and timing of shipments.
For the full year, worldwide to 70 revenues were approximately $1,900,000,000, an increase of 2% versus prior year. We recorded U. S. Revenues of $1,850,000,000 internationally. Overall, we were very pleased with the performance of our MS business in 2019 and are focused on maintaining the resilience of this franchise in light of new competition entering the market.
Let me now move on to SPINRAZA. Global 4th quarter SPINRAZA revenues were $543,000,000, a 16% increase versus the prior year, and relatively flat versus the 3rd quarter. In the U. S, SPINRAZA revenues for the fourth quarter of 2019 were 243,000,000 an increase of 3% versus both Q4 2018 and Q3 2019. The number of patients on therapy in the U.
S. Increased 2% compared to the end of third quarter of 2019, with growth coming from both the pediatric and adult patient segments. We continue to make strong progress with adults as more than 50% of the new starts in Q4 were adults and growth in adults exceeded our overall patient growth. As a reminder, the adult population is the largest segment of the market. We have continued to see an impact from gene therapy within the infant population, which represents approximately 5% of the total SMA market.
Outside the U. S, SPINRAZA revenues in the fourth quarter of 2019 were $300,000,000, an increase of 28% versus the prior year and a decrease of 3% versus the prior quarter. Outside the U S, we saw strong growth in patients across all regions, with broad growth from both existing and newly launched countries. The number of commercial SPINRAZA patients increased approximately 10% versus the third quarter of 2019. Despite strong overall patient growth, 4th quarter ex U.
S. SPINRAZA revenues decreased slightly versus the third quarter this year due to a combination of loading dose dynamics country mix, the timing of shipments in certain markets and pricing dynamics. Overall, we were very pleased with SPINRAZA's performance again this quarter, as we saw continued patient growth across the large mature markets and strong uptake in the emerging markets. Additionally, more than 50% of our revenue came from outside the U. S.
And there remains significant opportunity to reach additional patients, particularly outside the U. S. For the full year, worldwide SPINRAZA revenues increased 22% to $2,100,000,000, driven by 9% growth in the U. S. To $933,000,000 34% growth outside the U.
S. To 1,200,000,000 Let me now move on to our biosimilars business, which generated revenues of $196,000,000 this quarter, growing 25% versus the prior year. We estimate that we have more than 200,000 patients receiving treatments with our 3 anti TNF biosimilars, which is a significant increase of approximately 70 70% versus the prior year. Bene Poly is the leading Enbrel biosimilar in Germany, the UK and Italy. Klatsabi is the most prescribed to REMICADE biosimilar in Italy.
And IMRALDI is the leading HUMIRA biosimilar in major markets, such as Germany and UK, For the full year, Biosimilars revenues grew 35 percent to $738,000,000. Turning to our anti CD20 revenues, we recorded $601,000,000 for the 4th quarter, an increase of 12% versus the prior year, primarily driven by OCREVUS royalties. Full year anti CD20 revenues were $2,300,000,000, a 16% increase versus 2018. In the 4th quarter, we saw the 1st entry of in biosimilar. We expect additional biosol entrants in 2020, which we expect will put further pressure on Rituxan revenues.
Also as a reminder, our royalty rate on U. S. Sales of OCREVUS resets every calendar year. Total other revenues were $146,000,000 in the 4th quarter, a decrease of 12% versus the prior year due to the timing of shipments. Other revenues were $708,000,000 for the full year, an increase of 21% versus 2018.
As a reminder, other revenues in the first quarter of 2019 benefited from our large one time In addition, note that other revenues are variable and difficult to predict. Let me now turn to gross margin performance. Q44 2019 gross margin was 88 percent of revenues versus approximately 86% in the fourth quarter of 2018. The improvement in gross margin was percent relatively flat compared to full year 2018. Q4 R and D expense includes $63,000,000 related to the transaction with Samsung BioEPis, the $45,000,000 opt in payment we made to Ionis related to BIIB080 and $30,000,000 related to our collaboration agreements with KemPhore Therapeutics And Catalyst Biosciences.
Full year GAAP and non GAAP R And D Expense was 16% revenue Q44 non GAAP SG and A expense was 18 percent of revenue or $662,000,000. Both GAAP and non GAAP SG and A increased versus the prior quarter primarily due to increased commercial and medical investments as well as the timing of spend on G And A. Full year GAAP SG and A was 17 percent of sales or $2,400,000,000. Full year non GAAP SG and A was 16% of sales or 2,300,000,000 GAAP other expense, which includes interest, was $49,000,000 in the 4th quarter and GAAP other income was $83,000,000 for the full year. Non GAAP other expense was $50,000,000 in the 4th quarter $110,000,000 for the full year.
The difference between these GAAP and non GAAP results is driven primarily by gains on strategic investments, GAAP and non GAAP tax rate was approximately 16%. Compared to the prior year, GAAP and non GAAP tax rates for both the full year and the fourth quarter of 2019 benefited from a nonrecurring change in the company's tax profile in 2019 and the sale of the remaining portion of higher tax inventory in 2018 due to intercompany effects. Furthermore, the GAAP rate also benefited from the unfavorable prior year effect of U. S. Tax reform in 2018.
Our weighted average diluted share count was approximately $178,000,000 for the 4th quarter $187,000,000 for the full Throughout 2019, we repurchased approximately 24,000,000 shares at an average price of approximately $2.49 for total value of approximately $5,900,000,000, including approximately 7,700,000 shares in the 4th quarter for a total value of approximately $2,100,000,000. As of the end of the year, we had a total of approximately $6,300,000,000 in share repurchase authorization outstanding, including the new $5,000,000 plan approved by the board in December of 2019, which now brings us to our diluted earnings per share, In the fourth quarter, we booked GAAP EPS of $8.08, an increase of 71% versus the fourth quarter of 2018. And non GAAP earnings per share of $8.34, a 19% increase versus the prior year. Was $31.42, a 46% increase versus 2018 and non GAAP EPS was $33.57, a 28% increase versus 2018. We generated approximately $2,000,000,000 in net cash flows from operations in Q4, and approximately $7,100,000,000 for the full year, marking the final year where cash flows are impacted by payments to Fumaphar.
We ended the quarter with approximately 5,900,000,000 in cash and marketable securities and 6,000,000,000 in debt. Let me now turn to our full year guidance for 20 20. We expect revenues of approximately $14,000,000,000 to $14,300,000,000. We anticipate GAAP and non GAAP R and D expense to be between 15% 16% of revenues. We expect GAAP and non GAAP SG and A expense to be approximately We anticipate our GAAP and non GAAP tax rates for 2020 to be between 18% to 19%.
And we anticipate full year 2020 GAAP diluted earnings per share results of $29.50 to $31.50 and non GAAP diluted earnings per share to be between $31.50 to $33.50 It's important to note that this guidance does not include any impact from potential acquisitions or large business development transactions as both are hard to predict. This guidance does assume our proposed transaction with Pfizer closes. Our guidance also assumes a stable share count 18 and no change to foreign exchange rates. Importantly, our guidance also assumes no generic competition in the U. S.
For TECFIDERA in 2020. And assumes additional commercial and R and D expenses related to aducanumab. This guidance reflects our best assumptions as of now as a reminder, we will provide an update mid year on our 2nd quarter earnings call. I'll now turn the call back over to Michelle for his closing comments.
Thank you, Jeff. We delivered strong performance in 2019 with growth across all of our core business areas, double digit earning growth versus a year ago and strong execution across each pillar of our strategy. For 2020, we aim to continue our momentum by executing well on our strategic priorities across MS, SMA biosimilars and our pipeline with a priority focus on the U. S. This includes implementing the thorough go to market model, hiring the sales force, building out our medical teams and preparing for market access.
In addition, we are actively engaging with regulators outside of the U. S, including Europe and Japan. Beyondadalupe Mabbo, our pipeline is maturing. We now have 6 programs in Phase III and 27 clinical programs overall, an increase from 17 just 3 years ago. We have multiple near term opportunities for value creation, including in Alzheimer's disease, ALS, stroke, lupus ophthalmology and biosimilars as we aim to build a multi franchise portfolio.
Between now and the end of 2021, we expect 11 mid to late stage data readouts, including phase 3 readouts for Topasen in ALS, BIIB-one hundred and eleven in Corrideremia and BIIB093 in large hemispheric infraction. And 8 Phase II readouts across MS Alzheimer's disease, Parkinson's disease of thalmorogy, schizophrenia, acute neurology and neuropathic pain. As the leader in neuroscience with asymmetric core capabilities, we believe that no other company is better positioned to continue to deliver breakthrough therapies for diseases of the center of the nervous system to address a significant and growing unmet medical need. We'll continue to execute on our core strategy to build a multi franchise portfolio across our core and emerging growth area, I want to reiterate our commitment to maximizing returns over shareholders and bringing innovative therapies to patients over the long term. These demands that we continue to locate 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 investment we make.
I'd like to take a moment to discuss our broader purpose as an organization as we aim to pioneer science for the betterment of humanity. This includes doing the right thing for patients, our employees, the environment and the community, all of which we believe contributes to a long term sustainable shareholder value. I am proud of what Biogen stands for, and I believe this approach positions us well to be a sustainable organization over the long term as we remain focused on being the leader in neuroscience to address the tremendous societal needs in this space. Finally, I would like to thank our employees around the world for their dedicated to making a positive impact on patient's life and all of the physicians caregivers and participants in our clinical development programs, our past and future achievements could not be realized without a passion and commitment We will now open the
Your first question comes from the line of Jeff Porges with SBB Leerink. Please go ahead.
Thank you very much, and congratulations on the quarter and the results and all the progress. Just a couple of questions, Jeff, on the guidance. Could you talk about what assumptions are built into your guidance about the effect of the the Risdiplam imminent launch on SPINRAZA. And also, just, have you incorporated the full launch costs for aducanumab, sales force and everything. You mentioned that, but is it fully budgeted in that guidance?
Thanks.
So thanks for the question, Jeff. So with regard to Risdiplam, we are assuming that that product does launch. And so we're anticipating as everyone else's to kind of see the data and kind of what it means. We just remind people that we have ten thousand people on therapy today doing very, very well with a very low continuation rate. So we'll see kind of what happens in the data and how that product is received, but certainly there's a lot of growth opportunity for us ahead With regard to aducanumab, we're not going to give specific perspective numbers in terms of to launch.
But I would just point you back to looking at the SG and A guidance, which is up quite a bit from a percentage perspective and you get a sense of the amount we're spending year over year relative to that, that we spent last year. And that is, I think, the prudent thing to do given this significant opportunity ahead of us, which we're quite excited about.
Your next question comes from the line of Terence Flynn with Goldman Sachs.
Great. Thanks for taking the question. Maybe just two for me. Just wondering if you can give us any more detail on what's gating to the aducanumab filing. And then are you expecting a priority view?
And then the outlook in terms of the ex U. S. Regulatory filings there, do you have a similar level of confidence in filing in both Europe and Japan as do in the U. S? Thank you.
Hi, Terrence. This is Al. We it's basically a matter of putting together documentation the electronic common technical document. It's an electronic document with hyperlinks, etcetera. It's a matter of assembling all that and submitting that to the FDA.
And in terms of the engagement, we've been engaged with them since last, the first Type C meeting last June. And it's been very constructive. It's I've never, this is a unique situation to me. It's pretty unusual, I think, across the industry. But I'll say that it's, it's been there's been a high level of constructive engagement ever since, last June.
And with respect to the other regions, we have started our engagement with them, but it's still early days, but we do anticipate that we will be filing at some point in those other regions as well at some point.
Your next question comes from the line of Ronnie Gao with Bernstein. Please go ahead.
Good morning. Congratulations on the results and thank you for taking the questions. You've mentioned you're beginning to the redosing trial. I wonder if you can just tell us a little bit about what you're trying to achieve with that trial. Essentially, now that you've got the protocol, what are the points and when what is the data that we should see from that?
And then second on VUMERITY, can you describe a little bit the launch lines here. I guess it didn't really make commercial step yet. Can you talk a little bit about whether you intend to give it the same kind of parity business model to TECFIDERA or will there be some things you do with VUMERITY that in terms of access, support and so forth? That will be better or worse than TECFIDERA?
Hi, Ronnie, it's Al. Well, the main reason for the redosing study were humanitarian reasons. You know, we had all these patients who had volunteered to be in our clinical studies. They helped us develop edgucanumab. We felt we owed something to them.
Any of them had expressed a desire to the investigators that they wanted the drugs. So, so that's the primary reason as I said on, in my notes that, in my script that, it's a single arm study. Basically, every patient gets titrated up 10 milligrams per kilogram aducanumab. And all patients who were in prior studies, including placebo patients are eligible in a single arm study, the main thing you can really look at is safety and tolerability. And we had always envisioned doing a long term extension study.
In fact, we had one in place to evaluate long term safety and tolerability. And so that's the primary, of the study. In addition, of course, we'll answer we'll take a look at efficacy as best you can in a single arm study, because we would be interested in continued if there's durable effect, obviously we'll be looking at amyloid and other biomarkers And we'll also see whether or not the treatment gap had any effect on these kinds of markers.
So Ronny, concerning the second part of your question with the superior to take GI to the high density we have the opportunity with VUMERITY to strengthen the overall Fumarate portfolio. But TECFIDERA remains front and center in our promotion, you see the performance we continue to support. And again, a key metric will be, to increase the share of the start fumarate down the road. We are pleased with the access to date that is superior to what we seen from competition a few months after launch and for some competitor 12 months after launch. So we are pleased with the access We monitor very closely the start forms and the grads.
We are pleased to see so far that there is more start forms being issued extech than tech. So this is a but it's still the beginning. It's a bit too early. We'll come back with more color when we have more data.
Your next question is from the line of Phil Nadeau with Cowen and Company. Please go ahead.
Good morning. Thanks for taking my question. It's actually on Tech Fitter in the IP. I believe we're going to get a decision in the IPR next week. Can you remind us in the case where the IP were to fall, what would be the next steps?
What is the appeal process there? Then secondarily, what is the status of the court case? Can you give us an update on the timelines there? Should the IPR actually go your way next week?
Yes, so it's Jeff. So there is a expected decision from the IPR perspective, no later the end of 1st week of February. So that'll be the 1st 3 decisions. Depending on how that goes, If it goes into our favor, that's great. If it doesn't, we plan to appeal and the appeal process typically takes 12 to 18 months.
Two other cases, West Virginia and Delaware are expected to read out some point mid year, plus or minus a month or 2. Depending on how those go, those go our way. That's great. If not, we'll plan to appeal, and the appeal period, again, tends to take 12 to 18 months. So, we'll we obviously await kind of the results of that.
We do believe we have valid patents, nonetheless these outcomes are difficult to predict. There's a number of considerations that need to be weighed. There's obviously multiple decisions that we just talked about. Does the appeal periods And then there's handicapping whether or not people, if we're unsuccessful, we'll launch at risk. So it's difficult to predict in the short term.
So we'll, will kind of keep people apprised that kind of the developments, as we move our way through the year.
Your next question is from the line of Omar Rafatt with Evercore. Please go ahead.
Hi, thanks so much for taking my questions. Al, I just wanted to focus on Alzheimer's per minute, if I may. And it's very clear that FDA has a long history of approving CNS drugs. Which have failed and or negative trials in the past. However, every time FDA goes down that direction, I find that the pool results across every single thing.
So my question is, few pool results across Engage, IMerge and phase 1B, what does that look like? I'll be very helpful to understand. And also, how many post hoc analyses were done before you guys arrived at the protocol version 4 population? I mostly asked because I'm trying to understand how we should think about what should be the P value given all the splits that theoretically should be thought about before we arrived at the PV-four?
Omar, I mean, sorry, Omar, this Alta and Rock. I, I, we haven't disclosed the results of any other kinds of analyses, including pooling or subsets So we're not going to do that this morning. But I would say that, you know, I would not assume that, I mean, when you look back in 3 of proof drugs. I wouldn't say it's always the case that pooling is done. I think that there's, there are exceptions to that.
And so I would not assume that here. And, and let's see. Your question, the other question was how many post talk analyses You know, we did say it was postdoc, but I don't remember how many there were.
Your next question is from the line of Jeff Meacham with Bank of America. Please go ahead.
Good morning guys. Thanks for the question. Just have a few. On SMA, in clinical development, patients on Zolgensma switch back to SPINRAZA, curious if you guys have seen evidence that this is occurring in the real world. And then, Al, bigger picture question Alzheimer.
So if I assume that a beta antibody is an anchor therapy, when we looked on the road at combination approaches, is there sort of a fast path to derisk other words, do you feel like FDA? You could look at surrogate markers such as pet imaging initially and then down the road, look at cognition. Just want to get sense for looking at post aducanumab? Thanks.
Your first question was about SMA and Zolgensma. I mean, I don't really consider that switch back, if you will, because if they've had Zolgensma, arguably that they're still on it, if you will, they're getting the effect of the gene therapy. So in some ways, it's like a combination of adding SPINRAZA. We have heard about that. It does happen in the real world.
And you might want to, you might wonder why people are doing that. I think it's because the parents and the physician feel like there might be more room to improve. And so that's what I'm, that's what I hear from in the real world. But, in terms of data from that, we are starting to collect that data, but we have we don't have any conclusions at this point. But we are because it's happening in the real world, And since we're very interested in real world evidence, we are starting to collect that data.
In terms of Alzheimer's in combination, I mean, one of the reasons why we built the pipeline the way we did was that we had always envisioned combination therapy. And then first, obviously, to combine a aducanumab or BAN2401 with would be an anti tau or a tau ASO, something that affects tau. We were actually pleasantly surprised that aducanumab already affects tauco. So we'll have to keep that in mind. But nevertheless, I think the most obvious thing to do would be to combine with tau as the next step.
And it may be that there are certain stages of the disease that need the combination more than other stages. And, and in terms of a fast track, yeah, we will employ biomarkers, not only of the toxic proteins that were trying to reduce a beta and tau, but also potentially other kinds of biomarkers that look at, additive effects in a more expedient way. But, you know, I mean, ultimately I anticipate we will need to show some effect of the combination on reducing clinical decline further. I think that will still be important unless you can't do it. In other words, if you're in an early stage of Alzheimer's where there's no cognitive impairment, you may not be able to do it where biomarkers may, alone, may be the only approach.
Your next question is from the line of Michael Yee with Jefferies. Please go ahead.
Thanks for the question. You had made some comments around preparation for aducanumab, including SG and A. Could you just put a little more color around, I guess, the work being done in terms of timing of when you actually expect the sales force to be on? And maybe some comments around what are hearing from payers and what they would, how they are putting their perspective this type of drug and what type of access to that type of would get. And then just a quick one also for Al, there is a Diane II study reading out.
I'm sure people will try to make read throughs into what this means the beta amort about this? Just maybe just a comment on anything to know or your perspective on that study. Appreciate it.
So, Michael, if I can get started with the long readiness. Actually, the work started more than 2 years ago with an understanding of the patient journey, you know, from origination to diagnosis, the referral dynamic that change from market to market and even within the U. S, which is different. I understand the different types of market within the it's the different segments. We have finalized the go to market for the U.
S. This has been approved and this is founded in our budget as this test. And the hiring has started, first with medical affairs, obviously, engagement with scientific leaders also at the community level is important. And, also, the bio manufacturing needs to be stepped up and be ready for eventually a large demand with the functional support okay, to support the increase, the increased engagement and team. In terms of price, it's still it's still early, even if we are making progress, we engage with stakeholders because, as you can imagine, There is almost no drug cost today.
So we are engaged with patient association, pharmacoeconomics, close to 3rd leaders and all the customers mostly in the U S and beyond the U S. Beyond the price, it's all about the access condition and the affordability. We know that the more we wait, the more transition, the people will transition to full blown assistance and loss of dependence, which caused so much the society So basically, we start engaging, and hopefully, we'll have all the incentives in that field in order to further invest in R&D. This is our belief. So good progress step by step, but we engage broadly, and we ask for advice and we listen.
Hi, Michael, it's Al. Diane too. So Diane is the, dominantly inherited Alzheimer's network. So obviously in the patients. Amyloid is likely to be causal because most of the, damage inherited mutations that lead to all, spondylolzheimer's disease, are mutations either in APP, the amyloid precursor protein or enzymes that process it.
So, and so I think that these are very interesting studies. My understandings that solenizumab and gantenerumab are being tested. If the results are positive, I think that that would lend further support to the amyloid hypothesis. If the results are negative, I'd want to see that there is evidence of target engagement and biological changes in the brain before I make any conclusions.
Your next question is from the line of Cory Kasimov with JP Morgan. Please go ahead.
Great. Good morning guys. Thanks for taking my question. I wanted to ask on capital allocation and given the company's current portfolio and pipeline considering prevailing dynamics. How do you look at the relative attractiveness between continued share repurchases considering the 6 plus 1,000,000,000 in dry powder you have there?
And business development opportunities. I guess, do you have enough bandwidth to do both in a meaningful way? And do you and how much of an appetite do you have on the acquisition front at this time? Thanks.
So, Crius, Jeff, thanks for the question. So we're in a good position from that perspective, right? We have no net debt as of the end of the year. In 2019, we generated $7,000,000,000 of cash flow, and we expect that we'll have a strong cash flow year again in 2020. So we've got the financial flexibility to do both.
And we have been doing both. Over the last 3 years, we've done 15 M and A, BD type transaction spending $3,500,000,000. And in the last year alone, we bought back 24,000,000 shares for almost $6,000,000,000. So our interest is strong in terms of building the pipeline. We've taken the pipeline from 17 clinical assets 27, significant increase.
And then of those 27, there's 11 that have important readouts in the next 2 years, 5 of which could have a meaningful impact on the company. So we feel good about that. We'd like to continue to add to those assets and build the pipeline. But at the same point, we have $6,300,000,000 of authorized share repurchase capability as well. So we'll continue to make good decisions that are in the best interest long term to shareholders and we'll have the capacity to do both.
Your next question is from the line of Matthew Harrison with Morgan Stanley. Please go ahead.
Hey, good morning. Thanks for taking the question. I had one for Al on 2 pipeline programs. Al, can you just comment why alert to ASO could be differentiated from the kinase inhibitors that we see in development. And then maybe just share your views on anti lingo NMS.
Has that changed since you initiated that study or any updated views there? Thanks.
Is a wonderful target, we believe, for Parkinson's disease, not only for this for patients with familial PD due to lork2 mutations, but also potentially even for sporadic Parkinson's disease. And, the ASO, I mean, it's another approach to, instead of inhibiting the enzyme with a small molecule, to reduce the levels of Lord 2. And it remains to be seen. One thing I will say about the ASO is that it's CNS because we give it intrathecally. It's only going to affect Lort 2 in the central nervous system, whereas a small molecule may have a effects on the enzyme and other places.
But I would say other than that, it's kind of early days for whether or not these drugs will be effective And in terms of anti lingo, the phase 2 study that we're doing now is different from the 1st phase 2 study. In the sense that we selected patients based on advanced imaging with, to be sure that they actually had the myelination based on MTR and actually had intact axons based on DTI. We also chose the dose that looked the most promising based on the 1st phase 2 study, And we're combining it with multiple different kinds of immunomodulators in the first trial. We only combined it with interferon, but now we're combining it with TechFIDERA, Tysabri as well as interferon to see whether or not the level of inflammatory disease in the brain affects remylination. And perhaps when you have less inflammation, the oligodendrocyte precursor cells may be able to, re myelinate better.
So So that's the difference and we'll find out soon whether or not the second trial is positive.
Next question is from the line of Jay Olson with Oppenheimer.
And thanks for taking the question. Could you elaborate on the rationale for studying BAN2401 in patients whose amyloid levels fall below the threshold of positivity? And is the goal here to create a complimentary positioning for BAN2401 in patient segments that would be distinct from aducanumab?
Well, we do view this we do view the 2 drugs as part of a a multi drug franchise. And we will use the drugs where they naturally fit the best. And and we'll need data for that. Just because they're not positive based on a visual read, it doesn't mean there's no amyloid accumulation. So I think that's the distinction.
And in some ways, the A3, 4, 5 study, look at between the two studies looks at both stage 1 and stage 2, both of the both stages as defined by the FDA guidance document that came out last year on the various stages of Alzheimer's disease. So I would say that those 2 studies evaluate both stage 1 and stage 2 and both are important to study, I believe.
Your next question will come from the line of Evan Siegerman with Credit Suisse. Please go ahead with your question.
Hi, guys. Thank you for taking my questions and congrats on the quarter. I'm just looking towards next week with the potential results in the IPR, if it were to not go your way, would you consider, reprioritizing re prioritizing your business development, priorities versus share repurchases? Or would you have to wait until you kind of see the results of the court cases midyear?
Thanks for the good question. We see a business development M and A opportunities as being independent from what happens next week or what happens? 6 months ago in March, we continue to remain. We are very engaged on BD opportunities, and the team continued to look at the at the opportunities to create value for the shareholders. And this will be independent from any event.
And just as a reminder, we ended the year with no net debt. And in 2019, we generated $7,000,000,000 in operating cash flow. So we've got the capacity to do both.
The final question will come from the line of Robin Carnow us with SunTrust. Please go ahead with your question.
Hi, thanks for the question. Just to give us some comfort as like investors and we think about Alzheimer's should it be approved given that you're given a huge amount of antibody. Can you give us any comfort around cost of goods and margins that it wouldn't be too harmful? I know you guys have very good manufacturing capacity, but that's still a lot of antibody. So when would we learn this And can you give us any comfort that the dollar amount to make this drug isn't extremely high that it would overburden the system?
Thanks.
Yes, so thanks for the question. So, it's obviously something we've been looking at for a while. And I'll say, I don't want to get into too much specifics with regard to that at this point in time, but we're comfortable, that given the nature of the the substance that we'll produce, there will be a fair margin, and it will do well economically.
So I'm going to turn it back over to Michelle for his closing comments.
Thank you all for being on the call. Return the page of a very strong 2019. And now the team at Biogen is ready for a very material 2020. And obviously, with a priority for a potential aducanumab, thank you for your attention.
Thank you again for joining today's conference. You may now disconnect.