On December 19, 2023, the FDA expanded approval of tralokinumab-ldrm (Adbry; LEO Pharma) to patients aged 12 to 17 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.1
The approval expanded on the previous 18 years and up indication.
To break down this expanded approval, Contemporary Pediatrics spoke with Weily Soong, MD, chief innovation officer, Allervie Clinical Research, who was part of the tralokinumab-ldrm investigative team.
The full interview transcript is below:
- Tralokinumab-ldrm is a fully human monoclonal antibody indicated for moderate to severe atopic dermatitis in pediatric patients aged 12 to 17 years.
- The FDA-approved dosing for tralokinumab-ldrm in this age group is 150 milligrams every 2 weeks, administered through a single injection.
- Clinical trials, including ECZTRA 6, demonstrated the efficacy of tralokinumab-ldrm in improving atopic dermatitis symptoms. The trials showed significant reductions in Investigator's Global Assessment (IGA) scores, Eczema Area and Severity Index (EASI-75) scores, and Numeric Rating Scale (NRS) scores compared to placebo.
- The safety data for tralokinumab-ldrm is favorable, with most side effects being site injection reactions. The study emphasized that these results were achieved without the use of topical steroid creams.
- Tralokinumab-ldrm provides a new treatment option for adolescents with atopic dermatitis, offering improved efficacy and safety, with the potential for achieving almost complete or completely clear skin.
Can you explain how the biologic functions for pediatric patients aged 12 to 17 years whose disease isn’t adequately controlled with topical prescription therapies? What are dosing indications for this age group? How is it administered?
Weily Soong, MD:
Tralokinumab-ldrm is a fully human monoclonal antibody that specifically neutralizes interleukin (IL)-13, and IL-13 is a key direct a key driver of inflammation in atopic dermatitis. Therefore, it is now indicated as we talked about, for moderate to severe atopic dermatitis. Il-13 has always an interesting cytokine. It's always been known to be one of the main driver of atopic dermatitis and then tralokinumab-ldrm is designed to neutralize IL-13. So, that's the reason why it's been very effective in atopic dermatitis. For ages 12 to 17 its FDA-approved dosing is 150 milligrams every 2 weeks, which is 1 injection every 2 weeks.
Can you explain why tralokinumab-ldrm was FDA approved and what was demonstrated in clinical trials (design, trial name, objectives and results)?
We were part of the ECZTRA 6 trial, the one that looked at the adolescents indication. Tralokinumab-ldrm was approved in the adult indication and from 18 years and up several years ago. It's was very much a natural progression to go into the pediatric indications. Atopic dermatitis is very prominent in children and a lot of atopic dermatitis, patients developed their disease at childhood. That's why it's very important to go down to the lower indications to try to reach that childhood level indication.
In the primary data that was used for the FDA filing, which was the efficacy and results of tralokinumab-ldrm-and it was monotherapy, so there was no topical steroid creams-the endpoint was 16 weeks. There were 98 subjects in the tralokinumab-ldrm 150 milligram every other week group. There were 94 subjects in the placebo group.
The main points were IGA which is an investigator assessment of 0 to 1 and 0 is completely clear and 1 is almost clear. IGA of 2 is mild, IGA 3 is moderate, and IGA 4 is severe. At the start of the study, these patients were IGAs of 3 and 4. One of the endpoints is to go from 3 to 4, to 0 to 1, and 21% of these patients achieved within 16 weeks and IGA of 0 to 1 versus 4% in placebo.
There's also another score called the EASI-75. What it does is it takes the different body parts like the head, the neck, the body, the trunk, the arms and the legs, and you individually score them. Then you look at their lesions and the severity, and it creates a composite score called the EASI. In EASI-75, it is the 75% reduction in that score and that is one of the endpoints in the tralokinumab-ldrm group. There was a 29% reduction in the EASI-75 as compared to the 6% and placebo. There were other endpoints like looking at the purity scores and reduction and daily itching scores or purity scores, and that's called the NRS score, and that was, in the tralokinumab-ldrm group, 23% had a greater than 4-point reduction in the NRS score as opposed to 3% in placebo. So, they all met their standard endpoints.
There were posters that were shown that went to look at the efficacy at 52 weeks, and the safety and 52 weeks and these posters were presented at the Maui Derm and Winter Clinical conferences. They showed that the IGA 0 to 1 continued to increase so that up to about 45% of patients had an IGA of 0 to 1 after 52 weeks. Then in the EASI-75 group, about 69% of patients had an EASI-75 reduction. It was also exciting to see that the EASI-90, which is a 90% clearance of your atopic dermatitis by 52 weeks, was at 43%. So, it really just shows you how the longer you stay on tralokinumab-ldrm, the more improvement you get.
When it comes to treating atopic dermatitis, how does tralokinumab-ldrm change the treatment landscape for this population?
The great thing is that we have so many more options now and especially at this age group. So, we now have 2 biologics now in this age group to treat moderate to severe atopic dermatitis, I think what's very important is that we can actually now talk to our patients and say, "Are you truly happy with your treatments?" Because I think in the past, we basically said, "Well, you really only have a couple of options in this age group and there's some pros and cons with safety and efficacy."
We really couldn't offer our patients much of a choice. Now, with tralokinumab-ldrm indicated in this age group, we now can actually say to patients, "are you truly happy? We could potentially do even better than what you're doing now". Also, as we talked about, if you have any side effects with the other treatments, or any safety concerns with the other treatment options, we've shown that tralokinumab-ldrm is very safe and very durable and the treatment effects are very sustainable well past 52 weeks. The longer you stay on this, the better your atopic dermatitis seems to get. What's been fun about looking at the results of this study, just the dramatic difference between 16 weeks and 52 weeks. It's really exciting to see that progression and how patients improve.
Another area is that we know that IL-13 plays a role in other atopic comorbidities, and we know that atopic dermatitis is associated with other comorbidities such as allergic rhinitis, allergic conjunctivitis, asthma, and food allergies. Atopic dermatitis is very much associated with these diseases. A biologic helping the atopic dermatitis could also potentially help other disease comorbidities, too.
Is there anything else you would like to add?
I would say that, again, the longer you remain on this, the better you get. It's amazing that we are now starting to talk about almost complete and completely cleared to clear skin. The IGA of 0 to 1 and the in EASI-90 are just goals that are now obtainable. I think in the past, we never talked about almost completely clear and clear. It's just been great to really reach those goals. Now. The safety data looks very good. Most side effects are site injection reactions.
The other thing that I want to also mention is that this was a monotherapy trial, so you weren't allowed to use any steroid cream. These were all results without steroid cream, so it just shows you just how tralokinumab-ldrm by itself is very effective. I think for the pediatric side of things is for general pediatricians. I hope pediatricians understand just how frustrating that disease of atopic dermatitis is. Especially for this adolescent age group, just understanding how important it is to control your atopic dermatitis. Atopic dermatitis is constantly itching, you have all these lesions, and they have profound effects on an adolescent's social life, school performance, and sleep. They also get very, very frustrated about how much skin maintenance they have to do and how many creams and lotions they have. So, I think for pediatricians, I would love them to recognize there's some wonderful treatment options now for atopic dermatitis and patients no longer have to suffer.
If pediatricians are ever worried about potential side effects of these drugs, I just tell them there is side effects of not properly treating the atopic dermatitis. There's just so many profound impacts on your social life and school performance and sleep with atopic dermatitis. Pediatricians and parents should recognize the side effects of not treating. Flares are a big part of this disease, it's not just an everyday lesion. So having flares and an exacerbations of atopic dermatitis can be just as frustrating as an everyday lesion. In fact, it may be even worse, because there are days that you're completely clear, and [the child says] "oh, my gosh, I feel good," and then out of nowhere, you get this flare, and they're just miserable for many weeks.
For some patients, they already knew what it felt like to feel good, and then all of a sudden, they're miserable again. So, I just wanted to let people know that in atopic dermatitis, you not only have to think about daily lesions, but you also have to think about the flares.
LEO Pharma Inc. announces US FDA approval of Adbry (tralokinumab-ldrm) for the treatment of moderate-to-severe atopic dermatitis in pediatric patients aged 12-17 years. LEO Pharma. Press release. December 15, 2023. Accessed January 25, 2024. https://www.businesswire.com/news/home/20231215374551/en/LEO-Pharma-Inc.-Announces-U.S.-FDA-approval-of-Adbry%C2%AE-tralokinumab-ldrm-for-the-Treatment-of-Moderate-to-severe-Atopic-Dermatitis-in-Pediatric-Patients-Aged-12-17-Years