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The novel OX40 inhibitor molecule showed significant benefit for patients in new EADV 2022 data. A lead author discusses its potential.
As the treatment fields for immunologic diseases including atopic dermatitis continue to broaden, investigators are seeking patient-tailored agents that fill cracks of care and refine current standards of therapy: what treats a patient for longer, better, and with an even greater rate of benefits?
A potentially emerging option in atopic dermatitis may be rocatinlimab, a molecule designed to inhibit OX40 that is currently in mid-phase trials.
In an interview with HCPLIve during the European Academy of Dermatology and Venerology (EADV) 2022 Meeting last week, study author Emma Guttman, MD, PhD, System Chair of The Kimberly and Eric J. Waldman Department of Dermatology and Director of the Center of Excellence in Eczema and Laboratory of Inflammatory Skin Diseases at Icahn School of Medicine, discussed her team’s new research into rocatinlimab, the components of the new potential agent, and the importance of their key outcomes in assessment.
HCPLive: Before we go into the clinical data, can you talk a bit more about rocatinlimab, its makeup and composite benefit? What exactly are we hoping to observe from this molecule?
Guttman: So this is a monoclonal antibody that is exciting, because it's a novel class of drugs. The targeting is a novel way to target atopic dermatitis. OX40 is involved in memory T-cells, and particularly activated in type 2 cells. When this study was designed—and I'm actually happy that I was part of that design, and I think we designed it smartly, I want to say—we already thought about the fact that maybe because of the potential involvement of memory cells, this may lead to long term efficacy. And we thought to design it in a way that will assess disease modification.
What new data were presented at EADV 2022?
Guttman: So the study has parts 2: Part A, in which the endpoint was at week 16, and part B that started at week 18 in which the patients on placebo were also put on drugs. So the primary endpoint was at week 16 but then the secondary endpoint was at week 36, after the placebo patients also had the drug. At week 36, everybody had started treatment, and then there was another 20 weeks of follow-up to assess for that long-term efficacy. And what we saw is that while the drug achieved in all dosesthe primary endpoint versus placebo, it's a drug that continues to improve over time. There is not a plateau at week 16. In fact, the efficacy was much better at week 36. And the patients who switched to the drug from placebo also improved a lot in that time. But importantly, at week 36, we saw that the highest 2 doses maintained the efficacy in about 90% of the patients, if not a little more than 90%, in the highest dose for about 20 weeks, which is really unusual. We don't see that with other drugs—that maintenance of response. And that is very meaningful because there is this potential for disease modification.
So, it had biopsies at baseline and weeks 8, 16, 36 and most importantly at 56—which is so unusual, because it's after you stop the drug. And then we had blood-based assessment from North America. So first, the biopsy study and the blood study both showed the same thing. They showed very robust manipulation of biomarkers, and continued increase toward the end of the treatments at week 36. There was a very big differentiation between drug and placebo at week 16, very clear-cut not only in lesional skin but also in non-lesional skin. And then we saw that the placebo patients that were put on the drug at week 18 started improving until week 36. But the unique thing about this drug is that the patients that stopped the treatment still maintained efficacy in biopsies. So that, I think is unique to this drug and I'm very excited about this presentation.
What is the rationale behind assessment into head and neck dermatitis with rocatinlimab?
Guttman: Head and neck (atopic dermatitis) is an area that is very important for patients, and with existing drugs sometimes the head and neck is not fully controlled. And there are some reports also that dupilumab for example, causes head and neck rashes. And the reason being is that dupilumab targets the type 2 immunity, but may not target well type 1 immunity that is involved, for example, in contact dermatitis. And rocatinlimab, from preliminary studies, seems to target both TH2 and TH1 immune pathways. And this is why we think that while it works well on atopic dermatitis, many of the patients with atopic dermatitis may also have contact dermatitis, and it may cover that as well. So what we showed here is that patients that were under studies and have moderate to severe involvement of the face, the drug works very well and there was a delta between improvement in the drug and placebo that was significant and meaningful to the patients. And we believe that this drug may provide a very important avenue for all patients with eczema, but definitely also to patients with facial eczema.
What are next steps with regard assessing rocatinlimab? Are there other regions impacted by atopic dermatitis that you'd consider assessing? Is it a long-term assessment? Where do we go from here?
Guttman: This drug works very well on the entire party, but sometimes you want to locate areas of special interest. So, the face is a very important thing for patients. Another important place for me is the hands and feet. These are areas that are usually more difficult to treat, but particularly the face, you know, that's your business card, right?