Overview of DERBY and OAKS Studies


Medical experts recap the DERBY and OAKS studies.

Ryan Haumschild, PharmD, MS, MBA: We have an exciting agent that’s newly FDA approved. I know a lot of patients and providers are excited. Dr Lally, I want to hear your thoughts on pegcetacoplan, as it’s now approved as a complement inhibitor. Could you discuss the clinical trial evidence for this emerging therapy? How are the studies designed? I know there are the DERBY and OAKS trials, maybe give us your impression of the significance of these clinical end points and your impressions of the results.

David Lally, MD: Absolutely. This is a landmark time in our field, as this is the first treatment, with pegcetacoplan, that has been FDA approved for the treatment of geographic atrophy [GA]. We’ve never had this tool in our tool belt to help our patients, as Dr Khanani mentioned previously. It’s a big deal that we have our first FDA-approved therapy ever. The pegacetacoplan trials were 2 very large global multicenter, randomized double-masked trials that were parallel, one called OAKS and one called DERBY. They randomized over 1200 patients all over the globe. These patients were randomized in the trial in a 2:2, 1:1 fashion to receive either pegcetacoplan as a monthly intravitreal injection, once a month for 24 months. Or they could have been randomized to a once every other month intravitreal injection for 24 months. Or they could have received sham monthly injections, or sham every other month injections for 24 months. The primary end point of these studies was the same, which was the change in the area of GA based on what’s called the fundus autofluorescence photograph from the baseline to month 12.

What we saw in the OAKS study, the primary end point was met, where there was a significant reduction at month 12 in the speed of growth of GA. However, in the DERBY study, the primary end point was not met. It was just missed on its P value. But as these patients continued to receive treatment in the second year, and we looked at the month 24 results, we saw that treatment with pegcetacoplan was capable of reducing the area of GA growth in both of these studies. It was statistically significant, although I should mention it’s a nominal P value because it was at month 24. The encouraging thing we saw was that the effect of the treatment appeared to increase over time. That’s what we would expect and what we would want to see. The patients who were enrolled in these trials were patients with advanced GA. They had to have a certain area of atrophy to be included in the trials. That area of atrophy was between 2.5 and 17.5 mm squared at baseline, so that’s a very large size of atrophy, meaning that these patients have pretty advanced disease.

As Dr Khanani mentioned, the hope someday is to be able to intervene earlier in the stage of disease before they get to this advanced stage. The other thing is that these patients live with this disease for the rest of their lives. Our clinical trials were able to show 1- and 2-year data, but these patients are going to be showing up to our offices for the next 10, 15, 20 years. If we can see after 24 months that these curves of growth are diverging for patients who received sham vs active treatment, that’s very encouraging. We hope that as the years progress, those lines continue to diverge and we see greater treatment effects of reducing progression over time. There is an extension study going on with both of these trials. It’s a 3-year extension trial, so we are going to hopefully have much longer-term data coming over the years. It’s encouraging to see that the FDA approved this therapy because of the strong month 24 data showing there was a statistically significant reduction in growth with both the monthly treatment of pegcetacoplan and the every other monthly treatment of patients.

Ryan Haumschild, PharmD, MS, MBA: It’s great to see that clinical improvement. Even like you said, a lot of us are looking for patients to have statistical significance within 1 year, but even seeing it out to 24 months is meaningful to a lot of these patients, especially how the disease continues to progress. I think a lot of the payers need to be thinking about that as well. A lot of times we might think about a 1-year snapshot in time, due to maybe a retail patient population that has high turnover in the plan, but you have other plans like employer groups where you look out to 3 years. So seeing that improvement definitely adds clinical value. Dr Khanani, I know you’re treating a lot of patients and you’re excited about these treatments as well, and we’ll talk about a few more. What is the impact of the DERBY and OAKS outcomes on your practice, and how do you see it transforming the treatment of GA?

Arshad Khanani, MD: I think Dr Lally did a great job overviewing the data. I think what we have learned from DERBY and OAKS is that the more you treat, the longer you treat, and the better effect you see in terms of separation when you look at the treated group vs the sham group. When we are offering this treatment to our patients, obviously, whenever we have an FDA-approved treatment, our responsibility as a physician is to offer it to our patients. Then talk about the risk and benefit of the treatment, and figure out if they are the right candidate for it. Patients need to be committed to their treatment. Obviously, the payers have to pay for the treatment, and I don’t see a reason why they wouldn’t pay for treatment because they have nothing right now. Nobody wants their patients or their workers to go blind. I think if you can preserve vision longer, it benefits everybody, society, the payers, and whatnot. None of the treatments we have come without any adverse events. Dr Lally talked about the efficacy data. When you look at safety, there are certain risks associated with complement inhibition, especially pegcetacoplan. We look at the label, there’s an increased risk of choroidal neovascularization, some risk of intraocular inflammation, as well as…neuropathy. I think we discuss the risk and benefits with the patients and then offer the treatment. If patients are willing to adhere to treatment, then it is our responsibility to offer it.

I think once it’s commercially available—it just got approved, but it’s not commercially available yet—then I think my conversation will be with all the patients with GA. Then we know that the patients who don’t have central involvement may respond better based on the post hoc analysis of the DERBY and OAKS data. That may be a patient population ideally to treat, but we’ll see. As a physician, I see myself talking about a potential [treatment] once the treatment is available to all my patients with GA.

Ryan Haumschild, PharmD, MS, MBA: That’s exciting. I think this is going to be an emerging area, having the first medication on the market. Let’s see how things go. Maybe we can do some real-world evidence evaluation, and look at the extensions of these studies, and utilize that in practice as we move forward. And it’s the first to come to market, but that doesn’t mean there are not others coming, as you both alluded to.

Transcript edited for clarity.

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