Our review sought to put the laudable goal of having a cure or meaningful treatment for Alzheimer’s disease approved by 2025 into the perspective of contemporary drug development. There are two main points from this paper:
- To be approved by 2025, a compound has to be in Phase 2 or 3 (possibly late Phase 1) now. This means that any drug available by 2025 already exists and is making its way – slowly – towards a 2025 target. It seems as though the public have little appreciation for how complex or time consuming drug development is. If few or no drugs are approved by 2025, the public may feel that neuroscience has failed a contractual agreement, whereas in reality we are simply seeing drug development exposed for its current slow progress.
- There are ways to shorten drug development timelines and the field should be addressing them urgently. Shortening recruitment time is the most obvious means of accelerating drug development. This is the most common neurodegenerative disease on planet earth and yet it often takes 24 months (or more) to recruit for an 18-month trial – many agree that this is ridiculous. Shortening recruitment to 6 months for Phase 2 and 3 trials should cut more than 2 years off the total development time. There are many tactics to accomplish this and we should be investing in them all:
- Raise the level of public awareness on the importance and availability of trials.
- Raise the level of public awareness about the availability of specific Alzheimer’s trials and how to get to them.
- Optimize trial site performance for screening, processing and randomizing trial participants.
- Broaden the inclusion criteria to make more Alzheimer’s patients eligible for them; this will also have the effect of making trial results more generalizable.
- Simplify trials to make them more acceptable to patients; patients and caregivers should help to design trials to get their insight into this aspect of trial construction.
- Provide transportation to trial sites.
- Provide portable screening unit to go to neighborhoods and doctor’s offices to screen patients and assess them close to home.
- Broaden the use of technology to assess patients and improve compliance.
- Engage caregivers in programs with trials to make trial participation a rewarding experience.
- Develop registries of well-characterized patients that can be referred to trials as soon as they are available.
- Work with large-scale patient organizations such as insurance companies and Medicare to develop incentives for trial participation.
- Work with physician groups to develop incentives for referring patients to clinical trials.
- Use adaptive designs, futility analyses, combined phase approaches (1/2, 2/3) and other strategies to shorten trial duration and optimize the use of patient and financial resources.
- Advance the cultural competence of Alzheimer’s trials to become attractive to populations of currently under-represented patient groups.
In addition to abbreviating recruitment times, other approaches such as creating a central, efficient Research Review Board (RRB) for multi-site trials would decrease redundancy and shorten time currently devoted to Institutional Review Board (IRB) review and approval.
Advocacy groups and Congressional and Presidential candidates are lobbying for increased NIH funding including substantial new funds for Alzheimer’s disease. This is terrific and we should be fully behind the groups and candidates that share our passion as scientists to find new truths and new treatments. At the same time, we need to educate the public that basic science advances take more than a decade to result in new treatments and cannot produce a drug by 2025 – only 9 years away!
Progress is being made in advancing new science and achieving some of the goals articulated above. The Global Alzheimer’s Platform (GAP) is promoting site optimization, use of trial registries, and development of a central RRB. Registries including the Brain Health Registry (BHR), Alzheimer’s Prevention Initiative registry (endalznow.org), and the Cleveland Clinic Healthy Brains Initiative (healthybrains.org) are all learning how best to educate the public and enlist eligible participants in trials.
2025 is an elusive goal and it is very unlikely that we will have more than a few new therapies for Alzheimer’s disease by then. It is even possible that no drugs will prevail in that time frame; so far we have a 100% failure rate of developing disease-modifying therapy for neurodegenerative diseases.
What can and must occur is a transformation of the drug discovery and development process to provide better agents based on an improved understanding of Alzheimer’s biology, faster means of testing agents, better biomarkers to get early read-outs on drug effects, more efficient trial sites with optimized processes and central RRB, and faster, more responsive regulatory review. New treatments are important, necessary and possible regardless of the timelines in which they are achieved.