Priya Singhal
Interim Head of Research and Development at Biogen
Thank you Michel, and good morning, everyone.
As Michel mentioned, we're enhancing our focus on dynamic R&D prioritization with the goal of ensuring a sustainable pipeline that can deliver on Biogen's vision of a multi-franchise portfolio. We will continue to invest in R&D in a disciplined manner, including pursuing new and in external opportunities with a potentially different risk-reward profile, encompassing those within our core neuroscience therapeutic areas as well as select investments in therapeutic adjacencies. This approach will be informed by emerging scientific data, as well as internal and external readouts. As part of our overall prioritization strategy, we may choose to accelerate, dominate, divest or partner certain programs.
In addition, we will continue to advance key capabilities such as functional genomics, patient identification, novel modalities, biomarkers and clinical outcome measures, the goal being to reduce risk, accelerate clinical development and increase the probability of success in achieving positive proof-of-concept. I will now share the R&D highlights of the quarter.
Starting with Alzheimer's disease, in addition to continuing the progress with lecanemab US filing in the Phase 3 study, Eisai presented data at the annual AD/PD meeting this past March, showing that lecanemab treatment in the core Phase 2b study resulted in a dose and time dependent reduction of brain amyloid, as measured by PET SUVr, and that the reduction of brain amyloid was correlated with changes in two important peripheral biomarkers of amyloid and tau pathology. Specifically, an increase in plasma A beta [Phonetic] 42/40 ratio and a decrease in plasma p-tau181, respectively.
Furthermore, these biomarker changes were correlated with clinical benefit, as assessed by the change from baseline in the Clinical Dementia Rating Scale-Sum of Boxes. Notably, however, these peripheral biomarkers gradually began to reverse upon discontinuation of lecanemab treatment at the end of the core study, suggesting that stopping dosing prematurely may allow re-accumulation of Alzheimer's disease pathology.
Eisai also presented additional information on ARIA from the lecanemab Phase 2b study. This included the incidents of [Technical Issues] in the open label extension where ARIA-E was observed in less than 10% of participants receiving 10 milligram per kg lecanemab biweekly, and a symptomatic ARIA rate of less than 2%, consistent with the core study. We look forward to further defining the safety and efficacy of lecanemab through the larger Phase 3 Clarity AD study.
Biogen and Eisai are currently evaluating subcutaneous dosing in the sub-study of the Clarity AD Open Label Extension, which will evaluate subcutaneous injections compared to IV infusion. This is in addition to the ongoing AHEAD 3-45 study evaluating lecanemab in people with preclinical Alzheimer's disease or prior to cognitive impairment, which was initiated back in 2020.
Beyond lecanemab, Biogen continues to pursue new treatments across molecular targets in Alzheimer's disease. This includes actively planning for the Phase 2 study of BIIB080 our Tau ASO, and initiation of dosing in the Phase 1 study of BIIB113. BIIB113 is a small molecule inhibitor of O-GlcNAcase or OGA, an enzyme believe to catalyze the removal of O-GlcNAc post-translational modification of the tau protein. By inhibiting OGA, we aim to increase the O-GlcNAcylation of tau to potentially inhibit tau aggregation, and thereby slow clinical decline. As Michel mentioned, with Aducanumab we are also continuing to collect data in our EMBARK re-dosing study, and working towards the initiation of ADUHELM Phase 4 post-marketing requirement study ENVISION.
Moving to neuropsychiatry, Biogen and Sage recently announced that we initiated the rolling submission of a New Drug Application to the FDA for zuranolone in MDD. We expect to complete the filing in the second half of this year. We were also excited to announce that is zuranolone Phase 3 CORAL study in major depressive disorder met the primary endpoint and key secondary endpoint. The CORAL study was a randomized blinded trial designed to assess rapidity of response, when zuranolone 50 milligrams is co-initiated with an open label standard of care anti-depressant or ADT, versus placebo co-initiated with ADT. As measured by the change from baseline on the 17-item Hamilton Depression Rating Scale.
Top line results showed that zuranolone co-initiated with ADT resulted in a statistically significant reduction in depressive symptoms at Day 3, the primary endpoint and the earliest time point measured, as well as over the full 2 week treatment period as compared to placebo co-initiated with ADT. Zuranolone was generally well tolerated with most treatment-emergent adverse events reported as mild to moderate.
In MDD, zuranolone has now delivered four positive randomized controlled trials in total, as well as important insights on repeat treatment from the SHORELINE Study, a large prospective naturalistic study in MDD. While these trials were designed to address different questions, we see a consistent profile of zuranolone that include: rapid reduction in depressive symptoms compared to the standard of care anti-depressant; a consistent tolerability profile with a low discontinuation rate due to adverse events, and without observed weight gain, sexual dysfunction or suicidal ideation; a short course of treatment that can be potentially taken as needed, and a flexible treatment approach that may provide optionality to HCPs and patients. This is an addition to positive data from the Phase 3 ROBIN Study of zuranolone at postpartum depression. We look forward to the Phase 3 SKYLARK Study readout in PPD expected by midyear, with an associated filing for PPD anticipated early next year. We look forward to potentially bringing a rapid onset, well-tolerated, oral antidepressant with sustained effect and a new mechanism of action to patients suffering from depression.
Moving to ALS, we previously reported that while the Phase 3 VALOR study of tofersen in SOD1-ALS, a rare genetic form of ALS did not achieve the primary endpoint of a statistically significant change on the ALSFRS-R at week 28 versus placebo, we did observe signs of reduced disease progression across multiple secondary and exploratory endpoints. We plan to present integrated data from the Phase 3 VALOR study and a new interim analysis of its ongoing open label extension at the upcoming ENCALS meeting in June. This interim analysis includes data from participants with SOD1-ALS who had the opportunity for at least one year of follow-up from the start of VALOR. Long-term data on measures of function, strength, quality of life and survival will be presented.
We also continue to recruit for ATLAS, a study evaluating tofersen in pre-symptomatic participants with a confirmed SOD1 mutation, while also supporting the global tofersen expanded access program, which includes approximately 120 people with SOD1-ALS to-date. For more than a dozen countries, we also remain engage with regulators on potential next steps of tofersen.
As you can see, 2022 is an important year for Biogen R&D with several important milestones expected as we continue to advance a diversified pipeline that contains a total of 32 clinical programs with 10 programs in either Phase 2 or being filed. These milestones include key regulatory filings mid-to-late stage readouts in both Alzheimer's disease and neuropsychiatry, initiation of late-stage studies in Parkinson's disease and starting a pivotal study in cutaneous lupus erythematosus, in addition to ongoing recruitment for two Phase 3 lupus programs in SLE, as well as planning next steps for BIIB131 stroke program.
In summary, we are taking actions that we believe will enable delivery of a number of potential first-in-class and best-in-class molecules to patients suffering from diseases with significant unmet needs.
I will now pass the call over to Mike.
