Hi, everyone. My name is Dr Andy Blauvelt. I’m a dermatologist and I’m a consultant, for a company that I own, Blauvelt Consulting LLC. I’ve retired from clinical trials, as of last year, but the work I’m going to be discussing today is part of work that I’ve done, over the last several years.

Q. What are the limitations of current therapeutic options for atopic dermatitis? (0:30)

Unlike psoriasis, we have a situation in atopic dermatitis where we have good drugs that have good responses, but we don’t have the level of EASI 100 or complete clearance like we have in psoriasis. If you look at the response levels, the one that’s typically looked at is IgA 01, which means clear skin or almost clear skin, and we see drugs that are in a 40% range for the biologics, which is good. So 40% of patients at that level and then up to 60% of patients at that level with the JAK inhibitors. We still need, improvements on efficacy to get even higher levels.

Then, like in all fields, fewer shots in the case of biologics is going to be better for patients. Survey after survey suggest that patients like the idea of fewer shots. That’s definitely a current goal for not only psoriasis patients, but with AD patients as well.

Q. Could you tell us about amlitelimab and its mechanism of action? (1:45)

Amlitelimab is a new novel, monoclonal antibody that targets a molecule called the OX40 Ligand or OX40L. That particular molecule is found on the surface of antigen presenting cells. When an antigen presenting cell presents an antigen to a T cell, an OX40 Ligand on the surface of the APC binds to OX40 on the surface of the T cell, and it allows for full T cell activation, that engagement.

When you have an antibody that blocks OX40 Ligand, you’re going to impair the engagement of the antigen presenting cell and the T cell,  impairing the activation of the T cell. We know in atopic dermatitis TH2 cells in particular that are found in AD are more dependent on OX40 and OX40 Ligand for their activation.

It’s attractive to think about blocking OX40 Ligand in the setting of AD. Amatilumab is now late in phase 3 studies. It is far along now. It’s been shown to be safe and effective in earlier studies and phase 2 studies. That’s the background on the molecule.

Q. What have earlier clinical studies indicated about the potential of amlitelimab in atopic dermatitis? (3:23)

What we’ve learned so far with amlitelimab, that’s been published or publicly available, is that the efficacy tends to be slower than drugs we have now. We see more of a peak response at the week-24 time point compared to earlier week 12 or week 16, like we see other drugs. That’s one thing we’ve learned.

The other thing we’ve learned is, in the early phase 2 studies, where we start patients for 24 months and then we take them off, we’ve learned that some patients have a very prolonged response off drug. So a remittive effect, if you will. So that’s another kind of key feature we’ve learned about amlitelimab.

Q. Could you summarise the aims and design of the STREAM-AD phase 2b trial? (4:24)

The STREAM-AD trial was a phase 2 study for amlitelimab. Different doses of the drug were used in the first 24 weeks, to try to come up with the best dose for the phase 3 program. For responders, meaning they had to be a responder at week 24, a small proportion stayed on drug, but the majority of responders were taken off drug. Again, to assess this long term remittive effect. Then that went out to week 52.

We have data now at week 52 of people who were on drug the whole time and then people who were on drug for 24 weeks and then off drug until week 52. That’s the interesting thing of the STREAM-AD design. It has these two phases, if you will, looking at not only short-term efficacy, what’s the best dose, but what happens when you take patients off drug.

Q. What were the key efficacy outcomes over the 52-week period? (5:34)

What I’m going to be presenting at EADV was looking at people that had a great response [to amlitelimab] at the beginning – we call that an EASI 90, so 90% of their eczema was gone. So, what happens to those patients when you take them off drug?

What I’m going to be showing is that in those super-responders, it doesn’t matter what their starting dose was, if they did great and then went off drug, nearly all the patients stayed doing great at week 52 off drug. So the numbers between those who stayed on drug and those who came off drug are just a little bit lower for the ones who came off drug. It’s very comparable across the board of the different starting doses.

The point is, if you do great on this drug with an EASI 90 in the first 6 months, you’re highly likely to stay doing great, even off drugs. I think that if if you do great at the beginning, you have a great chance of staying in remission for a long time.

Q. How did amlitelimab perform in terms of safety and tolerability throughout the study? (7:05)

It’s been a relatively safe drug so far in phase 2 studies. The week 52 safety data was published last fall in the Journal of Allergy and Clinical Immunology. There’s no new information, in terms of what I’m presenting, but it is looking to be quite safe so far from the phase 2 data.

Q. What are the potential clinical implications of these findings? (7:36)

We always are thinking about how is this is going to play out in clinical practice with dermatologists. I think it’s going to be interesting because I’m not sure exactly how it’s going to play out, because it’s a drug that has lower response rates than some of the ones we have now and it’s slower. That’s not good, we know no one wants a lower response drug or a slow response; everybody wants to get better fast.

The good parts about this drug that make it interesting for me is that you have this remittive effect, and you don’t have to keep dosing forever like you do with the other drugs that we have. It’s interesting to think about how it’s going to play out in practice and in the conversations dermatologists are going to have with with their patients. They might say, this drug may not be the best one for you in the short run, but it might be the best one for you in the long run, because you have the chance of being in remission for a long time.

I think that it definitely is going to have value and have a place, but just balancing long-term value, which is where I think the drug excels, versus the short-term inability to compete well with what we have. So how is it going to play out? I think it will be used in the right patients who are looking for that long-term remittive effect. I think we have a different mechanism with amlitelimab than what we’ve had before.

It’s also going to be important to study long-term safety with amlitelimab and drugs that are related to OX40 and OX40 Ligand, because we have not had drugs like this before. Whenever we’re dealing with a new mechanism of action like this, it is important to closely look at side effects over time and establish a long-term safety profile.