IQVIA’s partnership with the European Prevention of Alzheimer’s Dementia
Nearly 10 million new cases of dementia are diagnosed each year worldwide — one new case every 3.2 seconds.1 Alzheimer’s disease is the leading cause of dementia globally. There is no cure, and success in AD clinical trials has been elusive. Current AD treatments provide minimal short-term relief, but none slow disease progression.
The European Prevention of Alzheimer’s Dementia was formed as a public-private consortium designed to improve the understanding of the early stages of Alzheimer’s disease and deliver new preventative treatments. EPAD selected IQVIA to oversee a longitudinal study of 6,000 nonidentified patients that enables researchers to track development of Alzheimer’s disease symptoms.
Lynne Hughes, VP and head of medical CNS strategy at IQVIA, provides insights on how EPAD and IQVIA are contributing to this important research.
EPAD is celebrating five years since its inception. What has it accomplished?
We have 23 European sites enrolling subjects to the longitudinal cohort study, and they have screened 1,867 research participants and 1,554 are currently enrolled into our registry. In the next few weeks, we will have 30 sites open and actively recruiting subjects. This is the largest cohort trial in the world in this subject population. Our cohort contains data from all the subjects and covers cognition, biomarkers, genetics and imaging, and we have already published a number of articles, posters and papers regarding this cohort.
The aim of EPAD is to provide a trial-ready cohort of screened and eligible subjects for participation in an adaptive proof-of-concept clinical trial. By using the registry participants, recruitment is faster and more efficient, allowing us to expedite clinical testing of potential investigational products through the PoC stage of clinical development. In addition, we are able to gather data showing the natural history of the early development of AD — characterized via the ongoing biomarker, imaging and cognitive assessments — which will aid in our understanding of the etiology of the disease. We have currently undertaken more than 20 analyses on our data set to date with more planned, and EPAD is making the data available to researchers globally.
How is IQVIA contributing to this effort?
EPAD selected IQVIA as the only CRO to project manage the EPAD longitudinal cohort study. The project management team formalized holistic and integrated stage gate reviews to optimize engagement of key internal stakeholders at pivotal points in the project lifecycle, improve up-front delivery strategy, plan development prior to study start-up, and execute according to plans during conduct. These SGRs established a formal structured review and oversight process and have become an integral part of the project culture, fostering more transparency, communication and collaboration. This has helped remediate potential roadblocks, challenge assumptions and proactively identify and mitigate risks before they can escalate into issues, thereby improving predictability and reducing surprise for stakeholders.
Our global reporting tools are also being used to drive continuing compliance with agreed schedule and quality commitments and form the basis for reporting to stakeholders on status and progress versus plan.
In addition to managing the LCS trial, IQVIA was also selected to execute all the subsequent PoC trials, which will utilize the LCS subject registry and assess the efficacy and safety of investigational products submitted through this innovative trial system. This unique design will utilize a master protocol — a ratio of 3:1 active IP: placebo — for each arm of the trial, and we will combine the placebo arms across different IOs to increase the power of the trial for each assessed IP. This design has been developed by Scott Berry, a PhD statistician and president at Berry Consultants, a statistical consulting company specializing in designing adaptive and innovative trial designs, and is a first in the field of AD clinical trials. IQVIA will be managing this entire trial for all the IOs, and we will be copying the database for each IO to ensure confidentiality while still allowing sufficient functionality for the placebo arms to be combined for each client.
What are some of the ongoing challenges of this project?
One key challenge is ensuring sustainability and continuity of the funding to allow the research sites to recruit subjects into the LCS, which will feed subjects into the adaptive PoC trial. Another challenge is ensuring that we have a clinical trial, in a reasonable timeframe, for qualified subjects to enter. If they are diagnosed with preclinical AD, we do not want to delay them from participating in a clinical trial, because they could potentially benefit.
What is the hope for the future of EPAD? What is the goal?
We are moving into EPAD 2.0, which will see the start of the first intervention owner submitting their IP for the adaptive PoC trial. All the sites will then move into clinical trial mode and will be recruiting their suitably qualified registry participants into the clinical trial, testing the first IP through the EPAD system. The first IO has already been identified, and the sites are ensuring that future registry participants are recruited who are likely to fulfill the trial entry criteria for this new trial. In addition, there are a few more pharma/biotech companies who have also submitted their IPs for review by the EPAD executive to see whether they would be suitable as the second IO for this trial.
Can this be replicated elsewhere?
This is a pan-European initiative to prove whether we can produce a characterized trial-ready cohort to expedite recruitment into clinical trials. There is a similar initiative planned in the U.S. — GAP-TRC (Global Alzheimer’s Platform – Trial Ready Cohort) — which is looking to see how EPAD works out, take any lessons learned and set up a similar approach in the U.S. The reason this is important is because the recruitment rate for preclinical AD subjects ranges from 0.15 to 0.4 psm with an 80 percent screen failure rate for amyloid-positive subjects. For preclinical subjects, the failure rate is closer to 90 percent and, thus, the sites spend a huge amount of time and resources screening subjects — for a low recruitment rate. Thus, this EPAD approach could be a game-changer in the way we conduct AD clinical trials in the future.
You’ve been involved in AD research for some time. What are you most encouraged by? What is your greatest sense of frustration?
The frustration is the continuing number of failed trials. We start off these trials with hope and, unfortunately, it gets dashed, usually at the futility analysis. Even where we have had successful Ph Ib/IIa trials, such as PRIME by Biogen, the subsequent phase III trials, EMERGE & ENGAGE, failed to meet their endpoint and were terminated at futility. The translation between the early phase trials to the later phase trials has not proven effective. However, we are continually learning about this disease from ongoing and failed trials and from subject registries. While our understanding has increased, we admittedly still have a long way to go.
The disease is receiving international recognition as being a potential global crisis and, thus, many governments are taking this seriously and implementing steps to support an aging population — many of whom could be suffering from AD. There was a G8 mandate — championed by President Barack Obama and Prime Minister David Cameron — of “Cure AD by 2025,” which has raised global awareness of this crisis. We are now seeing new IPs under clinical investigation, albeit currently in the early stages of trial development. These are targeting novel targets, different approaches, and are extremely interesting.
It is generally agreed there is not just one type of AD but many sub-types that will need personalized approaches utilizing combination therapy attacking different biochemical / genetic targets. Compared to a few years ago when we were seeing mostly amyloid- and tau-targeting IPs, today we have a greater range of cutting-edge, novel compounds under development, and this strategy is good for the global fight against this disease.