Partnership With Patient Advocacy Groups Is Key to Clinical Trial End Point Selection


Erika Fullwood Augustine, MD, MS, the associate chief science officer of the Kennedy Krieger Institute discussed an aspect of clinical trial design highly relevant to gene therapy development for rare diseases.

Erika Fullwood Augustine, MD, MS, the associate chief science officer of the Kennedy Krieger Institute

Erika Fullwood Augustine, MD, MS
Credit: Kennedy Krieger Institute

Currently, many companies and institutions are seeking to treat rare diseases with gene therapy. Although, selecting meaningful end points for clinical trials in these therapeutic areas can be particularly complicated.

Erika Fullwood Augustine, MD, MS, the associate chief science officer of the Kennedy Krieger Institute, recently spoke on this topic at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD. Shortly after the conference, CGTLive® reached out to Augustine to learn more.

CGTLive: Can you give some background context for your presentation at ASGCT’s 2024 Meeting?

Erika Fullwood Augustine, MD, MS: I had the opportunity to be part of a wonderful panel (a series of talks) in collaboration with patient advocacy groups about cell and gene therapy and what the role of clinical research and this kind of partnership—what does it mean for moving the field forward? It was a fantastic session.

What was your presentation about?

I think that ASGCT this year, like in many years, is really exciting because of all of these advancements that are happening. I'm a child neurologist, I have a particular interest in people who have rare diseases and providing care for people with rare diseases. What we find is that we don't have enough treatments and so I find meetings like ASGCT so exciting because I can see what's coming, I can see that we can do better. Then as a clinician-researcher, the other side of that is I have the opportunity to think about whether we're ready for where the technology is going. My interests in particular are in a group of diseases called the neuronal ceroid lipofuscinoses: NCLs or Batten diseases for short. In these conditions, we don't have many treatments to offer. My role—the work that I do—is focused on being ready for those new technologies. Do we know enough about the conditions? Do we know enough about what's important to patients and families? Can we measure benefit, if one exists, when these new therapies move into trials? That's what I spoke about during that session.

How would you summarize the main takeaway of this for the broader healthcare community?

Partnership is key. It was really fitting that the session focused on patient advocacy groups. These groups are the ones who know the conditions, who advocate, who move forward the field, who push us as scientists, and really become phenomenal partners in making those kinds of advancements. The big takeaway is to start early. As soon as there is a sense that there is going to be advancement from a therapeutic standpoint, it is probably already a little bit past the time when the work should have started. There can be impact, actually right away, just by knowing more about the disease. Over the years, it does take time to build that foundation of approvable end points and of robust outcome measures. Finding and honing in on what's meaningful really takes partnership with patient communities. Through patient advocacy groups is a key way to do that. Starting from the idea and moving into the quantitative takes time. Start early.

What are some of the challenges remaining in this field?

There are thousands of rare diseases, maybe more, maybe as many as 8,000 to 10,000. They're all unique, rare conditions affecting small samples—with some commonalities of symptoms and features—but then each with their own distinct needs in terms of measurement. I think the scale and the urgency of the need is one major challenge.

Funding to support natural history work has been very limited in the past; that is changing, and it's improving, but still in a way, we're seeing a couple of studies launch at a time, when what we really need are broad approaches where we can advance a lot of learning across many diseases at once. That's not quite there yet, but hopefully on the horizon. Then I think in terms of the actual measurement—finding those endpoints—I'll go back to the NCLs, as an example: In these conditions, they're usually childhood onset, genetically-defined conditions that share common symptoms of blindness, dementia, epilepsy, and movement disorders, all together, but in different combinations that may unfold at different rates or different paces. There may be symptoms that are burdensome or impactful for one person that don't happen in another. Then you again have a small number of people. When you're talking about a tiny trial, where each person might be a little bit different in terms of their symptoms, sometimes it's hard to say this one endpoint, or these couple of measures are going to be the most important ones and the best ways to demonstrate benefit. We're still trying to find that balance of what kind of measures work well in small samples, have deep meaning for patients and families, and are also scientifically robust in terms of the analytical approach. We're still finding that sweet spot, but making progress, and these are some of the difficulties we face.

Is there anything else you would like to share?

I think perhaps I would just reflect on what an inspiring experience this year's meeting was, especially a number of the keynote speakers. Whether they shared information about their own journey in science (their career path) or if they presented the culmination of decades of work and advancements in the way that we can have much more nuanced targeting of specific cells and specific regions that can be selected, tailored for certain patient populations. The idea that we've moved beyond just the proof of concept and now are really getting into the nuances needed for the complexity of disease that we see is really just thrilling. It was a very exciting and inspiring meeting. I'm excited to see what comes ahead.

This transcript has been edited for clarity.

Click here to view more coverage of the 2024 ASGCT Annual Meeting.

1. Clinical trial endpoints - approaches to optimize natural history studies and engage patient advocacy groups. Presented at: ASGCT Annual Meeting 2024, May 7-10; Baltimore, Maryland.
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