Amlitelimab Data in Eczema Indicate Potential for Disease Modification

MedPage Today brought together three expert leaders for a virtual roundtable discussion on atopic dermatitis following the American Academy of Dermatology (ADD) annual meeting: Moderator Peter A. Lio, MD, of Northwestern University Feinberg School of Medicine in Chicago, was joined by Sarina B. Elmariah, MD, PhD, of the UCSF Center for Itch and Neurosensory Disorders in San Francisco, and Jennifer Soung, MD, a dermatologist and director of clinical research at Southern California Dermatology in Orange County.

In this episode, the panel turns to trial data on the investigational OX40 ligand inhibitor amlitelimab, with discussion focused on efficacy, itch response, safety, and the potential of a disease-modifying effect.

Following is a transcript of their remarks:

Lio: So amlitelimab is a drug that is being developed by Sanofi, and this is a non-depleting anti-OX40 ligand antibody. What’s really interesting about this is, I think the hot topic is, can this potentially cause some disease modification? Will there be a remittive effect or potentially even, starting to circle around the idea, could it be towards a cure? Could we treat patients, reshape the immune system, and then potentially be able to stop it beyond just spacing out the doses?

Now, we got some data that was shown as a late breaker. We got to see the phase III trials, COAST and ATLANTIS data. And I’d love to hear your thoughts about what we saw both in terms of efficacy and safety. Dr. Elmariah, would you like to start us off first a little bit on your impressions?

Elmariah: Sure. So I mean, I think the nice thing about amlitelimab is that it’s blocking the OX40 ligand, and it blocks T-cell expansion without actually depleting it, which is really, really important. So it’s going to be reducing multiple type 2 cytokines, IL [interleukin]-4, IL-13, even IL-5, IL-22, IL-17, IL-31. And because of that, it has a lot of potential for, I think, that control as well as long-term durability in terms of bringing about clearance and improvement in itch.

Now, they looked at monotherapy in the COAST trials, also with concomitant topical corticosteroids and calcineurin inhibitors in the SHORE trials. And they explored also different dosing frequencies. And essentially what they found looking in adolescents and in adults is that 40% of patients were able to achieve an EASI 75 [a 75% reduction from baseline in the Eczema Area and Severity Index] by week 24 with no plateau compared to about 20% in placebo. And then that was also about 48% in the SHORE trials with TCS [topical corticosteroid] and TCI [topical calcineurin inhibitor].

So what I think is nice — although I will say probably not quite as strong as some of the other data for other biologics — is they got patients achieving a PP-NRS [Peak Pruritus Numerical Rating Scale], a 4-point or more improvement in their itch scores, their Peak Pruritus scores, and about 22% to 24% of patients in the COAST trials, and about 33% to 38% in the SHORE trials by week 24. So it’s a little bit underperforming from an itch standpoint. However, it’s still giving a good long-term control.

And I think one of the issues that came up early on is that there had been, from a side effect profile, very, very safe drug, generally speaking. There were two reported patients with Kaposi sarcoma, both with risk factors. This was not actually seen in the longer-term studies, so no additional cases, but important to recognize that.