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[Colin Miller]

Hello, you're tuned into SNiPs, a reoccurring special segment from our ongoing series, Fractals: Life Science Conversations. Bracken is the professional services firm for life sciences and digital health organizations. Our intelligence ecosystem fulfils consulting, regulatory, marketing and analytics, an integrated and strategic approach.

The biomarker I spent a lot of time with, as you know, is DXA and its use in osteoporosis. And it's actually got a resurgence now in the GLP-1 arena because of the body composition measurements. And it has some interesting challenges to it.

And maybe just going to the DXA side, I mean, first of all, it had to be correlated, but it's not a perfect correlation with fracture. But the FDA accepted that if you did a fracture study or future work, you could use BMD. Are you aware of anything on the body comp side and how good that is at working for prediction of fat mass and muscle continuity, if you will, muscle preservation?

[David Raunig]

A little bit. I worked on a few studies with muscle mass, and I think it's important. I think that we're going to find it's important.

Muscle mass, certainly in an ageing population, and we have an ageing population, is going to be important to preserve muscle mass as you get older and reduce the probability of fracture. Some of the other biomarkers are derived biomarker scores, like the probability of fracture score. There's a fracture score that looks at a number of different radiological biomarkers in the bone.

And people at Columbia have been doing a lot of work in that and so have others. And I think that those are interesting biomarkers, but they are not qualified for use in all clinical trials. So, there are no biomarkers that actually are qualified for use as efficacy endpoints in clinical trials.

By qualified, I mean that anybody can use them without any more studies. So, no pilot studies. You don't need any more information.

You go right to the FDA guidance document and use the guidance document to guide you in the use of that biomarker. So, there are none of those, but there are quite a few that are used, that are qualified for use in a single clinical trial or a single set of clinical trials with the same population. And that really means that if you can demonstrate to the FDA that you can use this endpoint reliably to determine a clinical outcome, you can use it in your trial, but there's not enough evidence to make a blanket broad statement that that can be used in all clinical trials with the same indication.

So, what that means is that the quite onerous process of getting a biomarker qualified through the FDA as an efficacy endpoint, you still have to follow the same basic rigor, but you don't need tens of thousands of patients to be able to do that. So, you can go to the FDA, and for the imaging group, it's the DM, they changed their name, but it's the old DMIRM, so the Department of Division of Medical Imaging and Radiological Medicine. And you can go to them with enough evidence to show that it can work in your clinical trial, and you can do that from a pivotal trial, a Phase IIa trial, or even a Phase IIb trial, and take that information to go to a pivotal trial and possibly a confirmatory trial.

So, what that means, though, is that all of these biomarkers like DEXA and the trabecular bone score and everything else that we have out there, you can use them, especially in the case where, let's face it, the low-hanging fruit's been taken. We have a lot of rare diseases now that are not low-hanging fruit, still need solving, but the old biomarkers just don't work. So, the number of fractures or the length of the fracture or the healing time of the fracture just doesn't work.

So, we want other things to be able to predict or show response to treatment that don't take eight months to heal, and then you have to measure the fracture line. You don't have to measure the length of the fracture in the fibula, for instance. A year-long process to be able to collect that data to go to the FDA is feasible.

I've done it. It's become a little bit more rigorous than it was 15 years ago, but I've done it as little as just a couple years ago. And the FDA allows those to be used when other indications are going to fail.

[Colin Miller]

Fractals: SNiPs is brought to you by Bracken and available wherever you get your podcasts. Visit us at thebrackengroup.com or reach out directly on LinkedIn. We'll be delighted to speak with you.

I’m Colin Miller wishing you sound business and good health. Thanks for listening.