Eli Lilly & Co. (LLY) Business Update on Solanezumab Conference Call June 12, 2013 9:00 AM ET
Phil Johnson - Vice President of Investor Relations
Eric Siemers - Senior Medical Director of Alzheimer's Disease Team
Morry Smulevitz - Director Lilly Bio-Medicines Communications
Anthony Ware - Senior Vice President of Product Development
Tim Anderson - Sanford C. Bernstein
Mark Schoenebaum - ISI Group
David Risinger - Morgan Stanley
Tony Butler - Barclays Capital
Chris Schott - JPMorgan
Welcome to Eli Lilly and Company's webcast. My name is Cliff and I will be your operator for today. At this time, all participants are in a listen-only mode. We will be conducting a question-and-answer session at the end of today's presentation. Please note that this conference is being recorded.
Good morning. This is Phil Johnson, Vice President of Investor Relations. Thank you for joining us. We appreciate your interest in Eli Lilly and Company and hope you find the information we provide on today's call to be helpful.
This quarter, we will begin a new pivotal trial for Solanezumab called EXPEDITION3. Soon, we will be posting the trial design on clinicaltrials.gov and shortly thereafter, we expect to begin screening patients. Given the significant media and investor interest in late stage Alzheimer's disease trials, we wanted to provide you with details on this new trial and answer questions you may have.
Joining me on today's call are Dr. Eric Siemers, Senior Medical Director of our Alzheimer's Disease Team, Dr. Anthony Ware, Senior Vice President of Lilly Bio-Medicines Product Development including our Neuroscience business and Morry Smulevitz, Director Lilly Bio-Medicines Communications. Dr. Siemers will provide some brief prepared remarks and then Morry will moderate a question-and-answer session. Instructions will be provided prior to the Q&A session but I would highlight that you will be able to ask questions via the call-in number as well as the webcast.
Please keep in mind that during this conference call, we anticipate making projections and forward-looking statements based on our current expectations. Our actual results could differ materially due to a number of factors including those outlined in our latest Forms 10-K and 10-Q filed with Securities and Exchange Commission. Also, the information provided about our products and pipeline is for the benefit of the media and the investment community. It is not intended to be promotional and is not sufficient for prescribing decisions.
Now, I will turn the call over to Dr. Eric Siemers.
Thanks, Phil. I know that many of you participating in today's call have closely followed the development of Solanezumab. However, for the benefit of those of you that have not, I will summarize the results of our initial Phase 3 trials, EXPEDITION and EXPEDITION2 before going into the details of EXPEDITION3. Solanezumab is a monoclonal antibody developed by Lilly that binds the soluble monomeric forms of amyloid beta after it is produced allowing it to be cleared before it comes together to form beta-amyloid plaques. The rationale for treating Alzheimer's disease patients with an antibody possessing these properties follows the amyloid hypothesis, which posits that the accumulation of beta-amyloid in the brain influences the pathogenesis of Alzheimer's disease.
The EXPEDITION and EXPEDITION2 trials were designed to study Solanezumab as a potential treatment to slow cognitive and functional decline in patients with mild to moderate Alzheimer's disease. Each trial enrolled roughly 1,000 patients and was powered to detect treatment differences between Solanezumab and placebo based on the entire population of mild to moderate Alzheimer's disease patients. Within this entire population, there were certain subgroups of interest.
Since each trial on its own was not tailored to look at these subgroups, we prespecified certain analyses of data aggregated that is pooled across both trials. One of the main subgroups of interest was the subgroup of patients with mild Alzheimer's disease, as many members of the scientific community had speculated the treatment with an anti-beta amyloid therapy might be most beneficial when started earlier in the disease progression.
The trials were completed in 2012 and the data were presented last fall by the Alzheimer's Disease Cooperative Study Group at the American Neurological Association and clinical trials on Alzheimer's disease meetings. The primary endpoints, both cognitive and functional, in the overall population of patients with mild to moderate Alzheimer's disease were not met in either trial. In the prespecified secondary analysis of pool data in patients with mild Alzheimer's disease, we evaluated cognitive and functional measures more specifically relevant to patients with mild Alzheimer's disease.
For cognition, this was the Alzheimer's disease assessment scale of 14 item cognitive subscale or the ADAS-Cog 14. For function, this was the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living inventory subscale or the ADCS-IADL. On the ADAS-Cog 14, the pooled analysis of mild Alzheimer's disease patient showed a statistically significant slowing of cognitive decline with a P value of 0.001. This finding represented a 34% reduction in decline. On the ADCS IADL, the pooled analysis showed a slowing of functional decline at net statistical significance albeit narrowly with a P value of 0.045. This finding represented an 18% reduction in decline.
We also presented data showing that the difference in ADAS-Cog 14 and ADCS IADL between mild Alzheimer's disease patients treated with Solanezumab versus those treated with placebo increased at a relatively constant rate over the 18 months of the studies. In terms of safety in the pooled analyses, the only adverse event with an incidence of at least 1% that occurred statistically significantly more in the Solanezumab group than in the placebo group was angina, 1.1% versus 0.2%. The incidence of vasogenic edema or ARIA-E was approximately 1% occurring in 11 patients treated with Solanezumab and five patients on placebo, which was not statistically significant.
In summary, while the primary endpoints were not met in the EXPEDITION or EXPEDITION2, we were encouraged by the data in the mild Alzheimer's disease patient population. These are the first Phase 3 data with anti-beta amyloid agent that showed a slowing of cognitive and instrumental functional decline. More importantly, we are hopeful about what these results could ultimately mean for patients and their caregivers. We have also learned a great deal from these two trials and we have incorporated these learnings into the design of the EXPEDITION3 trial.
With that background, I will now discuss EXPEDITION3, including important enhancements we have made based on the results of EXPEDITION1 and EXPEDITION2. In addition, I will provide a very brief regulatory update before turning the call over to Morry for the Q&A session.
The primary objective of the EXPEDITION3 trial is to test the hypothesis that treatment with Solanezumab will slow the cognitive and functional decline of Alzheimer's disease as compared with placebo in patients with mild Alzheimer's disease. As was the case with our EXPEDITION1 and EXPEDITION2 trials, mild Alzheimer's disease will be defined by a Mini Mental State Exam score between 20 and 26. In EXPEDITION3, we will enroll 2,100 patients between the ages of 55 and 90 who have mild Alzheimer's disease. Patients will be randomized one-to-one to receive an infusion every four weeks of either Solanezumab 400 milligrams or placebo.
Patients may also receive concomitant treatment with stable doses of approved acetylcholinesterase inhibitors or memantine as these medications are typically considered standard of care for the symptoms of Alzheimer's disease. The double-blind placebo-controlled treatment period is designed to last 80 weeks, about 18 months, after which time patients may enroll in an open label extension in which all patients will receive Solanezumab.
The coprimary endpoints are the cognitive endpoint, the ADAS-Cog 14 and a functional endpoint, the ADCS instrumental ADL or IADL. Secondary endpoints include a variety of cognitive functional and quality of life measures, as well as changes in brain amyloid burden using florbetapir PET scans, the levels of Abeta species in both plasma and in the cerebrospinal fluid and volumetric MRI.
One key difference in EXPEDITION3 is that patients will be included only if at the time of screening they have a florbetapir PET scan or CSF result that is consistent with the presence of amyloid pathology. As I will describe in a moment, we believe this is an important enhancement to EXPEDITION3 that may allow us to identify those patients most likely to benefit from treatment with Solanezumab. This inclusion criterion will, however, mean that we will need to screen more patients to achieve the targeted enrollment of 2,100 patients
Across EXPEDITION1 and EXPEDITION2, the screen failure rate was just under 25%, while our best estimate is that the screen failure rate in EXPEDITION3 is likely to exceed 50%. While subject to change, given the number of patients to be recruited and the expected screen failure rate, we currently estimate that we will complete enrollment in EXPEDITION3 in approximately 22 months placing the last patient visit near the end of 2016. While we are not disclosing the specific assumptions used to power EXPEDITION3 we are confident that the trial is sufficiently sized to demonstrate a difference between Solanezumab and placebo on each of the coprimary endpoints. Our confidence stems from the pooled data in mild Alzheimer's disease patients, which I mentioned earlier, as well as from a number of enhancements we have made to EXPEDITION3.
First, we have increased the sample size. Recall that the pooled mild Alzheimer's disease subgroup across EXPEDITION1 and EXPEDITION2 showed a statistically significant slowing in cognitive decline as measured by ADAS-Cog 14 and in functional decline as shown by the ADCS-IADL. That pooled mild Alzheimer's disease subgroup was comprised of 1,322 patients. As I mentioned earlier, we will enroll 2,100 patients in EXPEDITION3, an increase of nearly 60%.
Second, as I mentioned earlier, in EXPEDITION3 we will include patients who have evidence of amyloid pathology and exclude patients who test negative for amyloid pathology. You may recall that in EXPEDITION1 and EXPEDITION2, we tested a small subgroup of patients for amyloid pathology using florbetapir PET scan. In those patients who were tested who had mild Alzheimer's disease, 26% were negative for amyloid pathology. It is possible that treatment with an anti-amyloid agent may have little effect on patients without amyloid pathology. This could potentially have diluted the treatment effect with Solanezumab in EXPEDITION1 and EXPEDITION2
Also, data from Lilly's and other companies' trials in patients with Alzheimer's disease, suggests that patients diagnosed with mild Alzheimer's disease but that test negative for Alzheimer's pathology do not experience much decline in their cognitive and functional abilities. These patients may have dementia that is not Alzheimer's and may not be appropriate candidates for a clinical trial testing in anti-amyloid beta therapy as a potential treatment for Alzheimer's disease.
Finally, the majority of sites selected for EXPEDITION3 have participated in previous Lilly Alzheimer's studies. These are sites that were successful in recruiting patients that have experience with our protocols. We also use what we learned in our prior EXPEDITION trials to train side investigators on the various clinical measures that will be used in EXPEDITION3. These enhancements, increased sample size, screening for amyloid pathology and focused site selection and training bolster our belief that the EXPEDITION3 trial is designed for patients who are most likely to benefit from treatment and is adequate power to show the treatment with Solanezumab slows the cognitive and functional decline in patients with mild Alzheimer's disease.
Now, let me provide a very brief regulatory update. We have design EXPEDITION3 with input from regulatory bodies. Based on these discussions, we believe that, EXPEDITION3, if successful along with these substantial preclinical and clinical data generated to date, we will meet regulatory expectations for submission and potential approval. The scientific and regulatory landscape in Alzheimer's disease continues to evolve and we look forward to continuing our collaborative relationship with the scientific community and regulators as appropriate. It is currently our understanding the various regulatory agencies may accept different data for submission in potential approval. In that regard, regulators may require EXPEDITION3 to act as a single pivotal trial potentially requiring statistically significant results below a P value of 0.05. We will continue to maintain dialogue with global regulators as necessary and appropriate as EXPEDITION3 progresses.
This concludes my prepared remarks and now I will turn the call over to Morry for the question-and-answer session.
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