Biogen Inc. (BIIB) Earnings Call Transcript & Summary

Olivia, would you like to introduce?

Yes. So next, we will hear from the Biogen Group. The presenter will be Dr. Samantha Budd Haeberlein, and Dr. Carmen Castrillo will be available for Q&A afterwards. And they will be presenting on EMERGE and ENGAGE top line results, Phase III studies of aducanumab in early Alzheimer's disease.

I'm going to present top line results from EMERGE and ENGAGE: Two Phase III Studies to Evaluate Aducanumab in Patients with Early Alzheimer's Disease. Aducanumab is an investigational compound and is not yet approved in any country. The aducanumab Phase III studies, EMERGE and ENGAGE, were 2 18-month randomized, double-blind, placebo-controlled Phase III studies. We randomized 3,285 patients at 348 sites. Patients had either MCI due to Alzheimer's disease or mild Alzheimer's disease. There were 2 dosing regimens, low and high dose, which were randomized 1:1:1 with placebo. The primary end point was CDR sum of boxes at 18 months. Each of the dosing regimens was stratified by ApoE4, the low dose if ApoE4 carriers were titrated to 3 milligram per kilogram. And ApoE4 noncarriers were titrated to 6 milligram per kilogram. At the beginning of the study, ApoE4 carriers were titrated to 6 milligram per kilogram in the high dose regimen and ApoE4 noncarriers were titrated to the target dose of 10 milligram per kilogram. Partway through the study, we amended the protocol to protocol version 4 where both ApoE4 carriers and noncarriers were titrated to 10 milligram per kilogram in the high dosing regimen. By week 78 in the high dosing regimen, the target number of doses was 14. The baseline demographics was well balanced across arms and across studies. And the baseline disease characteristics were also well balanced across arms and across studies and was consistent with the inclusion criteria. The primary and secondary endpoints were met in EMERGE and had a difference versus placebo of between 18% to 40% and all were statistically significant at the high dose. In the low dose, there was a numerical difference versus placebo, although this was not statistically significant. In the amyloid PET subgroup, there was a statistically significant dose- and time-dependent reduction versus placebo in both low and high dose. In the CSF sub-study, there was a statistically significant dose-dependent reduction in phospho-tau and a numerical difference versus placebo in the total term. In ENGAGE, the primary and secondary endpoints were not met. There was a numerical difference versus placebo in the low dose group. In the PET sub-study, there was a dose- and time-dependent reduction versus placebo, which was statistically significant. However, this, in the high dose, was lower than that which was seen in EMERGE. And we also understand that the median cumulative dose was lower in the ENGAGE subgroup, 126 milligram per kilogram versus the EMERGE subgroup at 140 milligram per kilogram. To understand the difference between the studies and the impact of changing the protocol, we define the population by a randomized cohort who had the opportunity for all 14 doses of 10 milligram per kilogram, and this is termed the post-protocol version 4 or PV4 population. If we compare the ITT population with the post-PV4 population, we can see that the post PV4 population in ENGAGE is consistent with the overall ITT population in EMERGE. A small tau PET sub-study was also conducted, and these results are pulled from both studies as they were all in the post-PV4 population. In 3 prespecified regions, we can see a dose-dependent statistically significant reduction in the medial temporal composite; and in the high dose, a statistically significant reduction versus placebo in the temporal and frontal composite. Shown here are the adverse events, which were well balanced across arms and studies and which were consistent with the patient population with the exception of ARIA-E. For patients who experienced an event for ARIA-E, the majority were asymptomatic. And those who did report symptoms, symptoms included headache, dizziness, visual disturbances, nausea and vomiting. ARIA-E episodes were generally resolved within 4 to 16 weeks, and the majority of patients were able to continue their investigational treatment. In summary, following study termination, analysis of a larger dataset showed that EMERGE high dose reduced clinical decline and in sub-studies showed an effect on disease-related biomarkers. ENGAGE did not reduce clinical decline. However, in a post-hoc analysis data from a subset of patients did support the positive findings of EMERGE. The most common AEs were ARIA-E and headache. And a redosing study is currently offering aducanumab to eligible patients who were actively enrolled in the aducanumab clinical studies.

Wonderful. Thank you. It seems that we have time for a couple of questions, and I'll try to sort through the Q&A just to see which are coming through at what time. One that I see is, are there any sub analyses on efficacy in mild AD patients versus MCI due to AD patients?

Thanks for the question. Yes, we have several prespecified subgroup analysis that haven't been presented yet, but this is one of them. Yes.

And one other quick one that I think you may have addressed but would be good to answer again is what types of medication side effects have you encountered?

As in AEs of aducanumab? Or...

Yes.