Priya Singhal
Head of Global Safety & Regulatory Sciences and interim Head of Research & Development at Biogen
Thank you, Michel, and good morning everyone. First, I want to say what an honor it is to serve as Acting Head of R&D at Biogen. Biogen has a track record in developing life-changing therapies in MS and SMA. With a deep and diverse R&D pipeline, Biogen aims to bring impactful medicines to patients suffering from neurological and immunological diseases characterized by significant unmet need.
As this is my first earnings call within this role, I would like to review a few areas that I'm especially excited about. First, we believe that Biogen has a unique opportunity to lead in Alzheimer's disease. Not only because we are advancing an industry-leading Alzheimer's pipeline, but also because of the proactive focus we have placed on continued data generation for aducanumab. This includes ENVISION, the planned post-marketing Phase 4 study, the ongoing EMBARK re-dosing study and obtaining real world data through the ICARE-AD registry.
We believe data from patients treated with aducanumab in the real world settings with greater drug utilization is the best way to complement the extensive clinical data generated on aducanumab to-date in addition to the ongoing and planned clinical trials. We also continue to gain potential insights from the aducanumab Phase 3 clinical data regarding Alzheimer's disease biology and the treatment effect of aducanumab.
On this particular point, Biogen recently presented additional data from the ENGAGE and EMERGE Phase 3 trials at the annual CTAD meeting last November. The important analysis of this data showed that in addition to reducing amyloid plaques in the brain, aducanumab treatment also resulted in changes in downstream tau Alzheimer's disease biology, specifically soluble phospho-tau or p-tau as seen in both CSF and plasma. In this analysis, we evaluated over 7,000 plasma samples from more than 1,800 subjects from the EMERGE and ENGAGE Phase 3 trials to investigate the effect of aducanumab treatment on plasma p-tau181.
The results showed a time and those dependent reduction in p-tau181 over 78-weeks with aducanumab treatment in both Phase 3 trials. The reduction in plasma p-tau181 from baseline to week 78 in this analysis was significantly correlated with change in amyloid PET over the same time period, and was also significantly associated with less clinical decline across all primary and secondary outcome measures assessing cognition and function in both studies. These findings are consistent with the hypothesis that aggregated forms of amyloid may mediate soluble tau phosphorylation.
With regard to our AD pipeline, we are excited about lecanemab our other anti-amyloid antibody in Alzheimer's disease that is being developed in collaboration with Eisai. In Phase 2, lecanemab did not utilize a titration period, demonstrated rapid and robust reduction of amyloid plaques and showed an ARIA incidence of around 10%. We look forward to the Phase 3 readout expected in the second half of this year.
Beyond our programs targeting amyloid, we are also pursuing a multi-modality approach focused on other targets in Alzheimer's. First, we have BIIB080, which is an ASO that we believe facilitates tau mRNA degradation and has demonstrated both a time and dose-dependent reduction of CSF phospho and total tau in Phase 1. We anticipate starting the Phase 2 study of BIIB080 by mid-year.
Second, we are also planning for the near-term initiation of a Phase 1 study for BIIB113, a small molecule inhibitor of O-GlcNAcase or OGA, an enzyme believe to catalyze the removal of O-GlcNAC, post translational modification of tau protein. Evidence suggests that O-GlcNacylation of tau attenuates aggregation. By inhibiting OGA, we aim to increase the O-GlcNacylation of tau to potentially inhibit tau aggregation and thereby slow clinical decline.
Having developed the first FDA approved therapy to address a defining pathology of Alzheimer's, we believe that Biogen is uniquely positioned with the right expertise, experience and access to modalities to lead in Alzheimer's disease. This is a complex disease requiring a multifaceted approach and continued investment as we work to build on the scientific learnings of ADUHELM and develop the next wave of potential Alzheimer's therapies.
I would now like to talk about depression. I believe that zuranolone with a novel mechanism of action may provide an important new treatment option for patients suffering from major depressive disorder and postpartum depression. The reported clinical data generated to-date from multiple clinical trials showed the following. First, in earlier studies, an improvement in depressive symptoms has been observed as early as day three. Second, zuranolone has displayed a consistent safety and tolerability profile with no observed evidence of weight gain, sexual dysfunction, euphoria or increased suicidal ideation.
Third, the SHORELINE Phase 3 open-label study showed that approximately 80% of patients, who responded to the initial course of 50 milligrams of zuranolone needed at most one additional treatment total during their time in the one-year study. Fourth, in the WATERFALL Phase 3 study, zuranalone reduced depressive symptoms in patients suffering from MDD both with and without elevated anxiety.
Fifth, zuranolone has shown improvements in depressive symptoms in postpartum depression. For zuranolone, we look forward to two Phase 3 readouts this year, the CORAL study in MDD and the SKYLARK study in PPD.
The next area I would like to highlight is stroke. Last year, we were excited by the results from the Phase 2 study of BIIB131, formerly known as TMS-007 in acute ischemic stroke. Administration of the current standard-of-care, pharmacological thrombolytic TPA, is limited to a short therapeutic window within 4.5 hours following the acute onset of stroke symptoms. This short time window is meant to mitigate the risk of intracranial hemorrhage, which is the most concerning adverse event associated with TPA.
In the Phase 2a study of BIIB131, acute stroke patients were randomized to receive BIIB131 or placebo out to 12 hours from their last known normal. The primary objective of the study was safety. And of the 52 patients, who received BIIB131, none experienced symptomatic intracranial hemorrhage, compared to one out of the 38 patients, who received placebo. This was despite an extended treatment window where patients, on average received BIIB131 at 9.5 hours after the onset of acute stroke symptoms.
Additionally, BIIB131 showed a statistically significant improvement versus placebo on the modified Rankin Scale, or MRS, a registrational endpoint of functional independence. Furthermore, the rate of recanalization or improvement of vessel blood flow in patients, who had a visible vessel occlusion was approximately 58% at 24 hours, in those who had received BIIB131, as compared to 27% of patients who received placebo. We believe BIIB131 may have the potential to be a best-in-class thrombolytic for the treatment of acute ischemic stroke by extending the time -- treatment time window out to 24 hours with an appropriate efficacy and safety profile. We are currently evaluating the next steps in the development for BIIB131.
In addition to BIIB131, we also continue to advance a Phase 3 study for BIIB093 in large hemispheric infarction based upon the effects observed on mortality and cerebral edema in the Phase 2 study. I would now like to turn my attention to specialized immunology. We currently have two Phase 3 assets in SLE, including dapirolizumab pegol in collaboration with UCB and BIIB059, our anti-BDCA2 antibody developed in-house at Biogen. These two assets represent potential first-in-class molecules in SLE.
BIIB059 also has the potential to be a first-in-class biologic in cutaneous lupus erythematosus or CLE. CLE is a skin-based autoimmune disease that can be associated with severe scarring and dyspigmentation. In the Phase 2 LILAC study, the CLE part of the study also met its primary endpoint by demonstrating a dose response of BIIB059 on the percent change from baseline in the CLASI-A score, a standardized scale measuring CLE disease activity at week 16 in individuals with CLE. Furthermore, a higher CLASI-50 response rate or number of individuals with a 50% or greater improvement from baseline in the CLASI-A score was observed in patients, who received BIIB059 at week 16. Based upon these results, we are currently planning to also initiate a pivotal study for BIIB059 in CLE this year.
Next, I will touch upon ALS. ALS has been a very key focus area for Biogen for many years. And we remain encouraged by the data from the Phase 3 VALOR study of tofersen, where despite missing the primary endpoint of a statistically significant change from baseline to week 28 in the ALSFRS, we believe there are trends favoring to a person across multiple secondary and exploratory measures of biological and clinical activity.
We are continuing to collect data in the VALOR open-label extension, and we are actively recruiting for the ATLAS presymptomatic study. Many SOD1-ALS patients have received access to tofersen through the global expanded access program, which is available in countries where local regulations permit it and where we hope to secure long-term access. Further, we are engaged with regulators to determine the next steps for the program.
Aside from the areas I've highlighted, Biogen continues to grow and diversify the R&D pipeline, which now includes 32 clinical programs. New additions include the exercise of the option with Ionis on BIIB115, an investigational ASO with the potential for extended dosing intervals in SMA, as well as the recent initiation of a Phase 1 study in Angelman syndrome, a rare genetic neurodevelopmental disorder that affects the nervous system and causes severe physical and learning disabilities with symptoms beginning in infancy.
Importantly, I believe that 2022 will be a significant year for Biogen's pipeline given the number of important readouts expected, including the lecanemab Phase 3 in Alzheimer's disease, key readouts in neuropsychiatry for both zuranolone in depression and BIIB104 in schizophrenia and BIIB078 in ALS.In closing, I believe Biogen has assembled an extensive pipeline of programs informed by generics, a deep understanding of disease biology, specialized modality expertise and digitalization. Therefore, I believe Biogen is uniquely positioned to shape the future of therapeutics in neurology and specialized immunology and make a difference in patients' and their caregivers' lives.
I will now pass the call over to Mike.
