Recent Developments

A picture is worth 1,000 words, maybe more when it comes to identifying dermatologic manifestations of disease across skin tones. Not knowing what you are looking at or for can result in missed or delayed diagnoses which can have severe consequences for patients.

The tell-tale sign of Lyme disease is its bulls-eye rash, but this may not be recognized in Black patients. This is the main finding of a new study by Dan Ly, MD, PhD, an assistant professor of medicine at the David Geffen School of Medicine at University of California, Los Angeles. The study appears in the Journal of General Internal Medicine. Dr. Ly spoke to Practical Dermatology® magazine about the findings, their implications, and what is needed to better educate physicians.

Why is this topic important to study?

Dan Ly, MD, PhD: Lyme disease presents first on the skin with a “bulls-eye” rash. But such rashes in Black patients aren’t well-represented in medical textbooks or even online. This may lead to physicians not recognizing such rashes in Black patients, which may lead Black patients to develop later complications of Lyme disease.

Describe the research and your findings.

Dr. Ly: I examined patients on Medicare and compared Black and white patients living in the same state. I found that Lyme disease is diagnosed later in Black patients than in white patients, so when it is first diagnosed, Black patients are much more likely to have later neurologic complications than are white patients. About 34 percent of Black patients showed neurologic signs of Lyme disease when they were first diagnosed, compared to only nine percent of white patients. Most tickborne infections occur during the summer, but Black people were also more likely to be diagnosed outside of the typical Lyme disease season.

What is the next step?

Dr. Ly: There have been greater efforts, particularly through online resources, to show what dermatologic conditions look like in patients with darker skin. This will hopefully help physicians better recognize what the rash of Lyme disease looks like in all skin types.

Many patients with psoriasis, atopic dermatitis (AD), and other common dermatoses are not adequately controlled. The majority of patients aren’t candidates for novel therapeutics, because they have less extensive disease. Enter Arcutis Biotherapeutics, a company focused on late-stage development of treatments aimed at unmet needs in psoriasis, seborrheic dermatitis, and AD. Their lead candidates include topical roflumilast, a PDE4 inhibitor, and ARQ-252, a topical JAK inhibitor. President and CEO Frank Watanabe, a dermatology industry vet, talks to Practical Dermatology® about Arcutis.

Arcutis is Focused on Meaningful Innovation

“With the massive consolidation of dermatology over the last 15 years, a lot of innovation in the dermatology space dried up. Yet, a lot of unmet need remains. Diseases like seborrheic dermatitis are being completely ignored by the drug industry.

“The founders of Arcutis saw an opportunity to build an innovation-focused medical dermatology company to start addressing some of the unmet needs that really weren’t being addressed.

“We saw a number of inflammation-driven diseases that needed better treatments. Additionally, there was exciting science going on in inflammation, which we knew we could leverage into dermatology. We don’t do drug discovery; we’re a drug development company. That pool of interesting science and new molecules was a key part of our strategy.”

Topicals: A Starting Point, Not the Sole Focus

“At the moment, our pipeline are all topicals, and we have some unique development capabilities in the topical space. The benefits of topicals are multiple. One is that you have generally less systemic exposure, you’re able to target the drug at the area of greatest need, so you tend to have better safety and tolerability.

“Our lead program is a good example of that. PDE4 inhibitors are very effective immunomodulating agents, but given systemically, they cause diarrhea, nausea, and vomiting. We’re able to get very high levels of PDE4 inhibition locally in a psoriatic plaque, seborrheic dermatitis, and atopic dermatitis lesions without that high level of systemic exposure.

“There are real concerns about the safety of systemic JAK inhibitors. Topical JAKs should have less systemic exposure and consequently fewer safety issues. However, we believe that AD is not the best place for a topical JAK inhibitor, as large body surface areas and impaired barriers in children can lead to substantial systemic exposure. We’ve been very careful about where we are investigating JAK inhibitors to try to minimize any systemic exposure, such as in vitiligo or hand eczema.

“The stratum corneum, over millions of years of evolution, is designed to do one thing—keep stuff out. It’s very difficult to develop topicals that effectively deliver drugs to the skin in the amounts you need. That’s where our formulation expertise has been a key part of our success.”

Drug Design Has Three Pillars

“We focus on designing drugs that are aesthetically pleasing for patients, because we believe that has a dramatic impact on patient adherence. We have three pillars to our strategy. The first one is a focus on biologically validated targets—things that have already been shown to work in dermatology. We’re not going after totally novel targets, because the probability of success is so low. The second pillar is finding best-in-class molecules. We always look for a molecule that’s better than what’s currently out there, because otherwise, why do it? The third is building a team with deep expertise, specifically in dermatology. For example, we now have six employees at the company who are dermatology clinicians, either MDs or NPs or PAs who are trained in dermatology; that’s a very high number. I don’t know of another drug company that has anything close to that.

“Once we’ve identified a target and a molecule, then the next step is designing a vehicle that is optimized for that drug. Because we have such deep formulation expertise, we can design each formulation around what that molecule wants.”

They’re Innovating Clinical Research

“The focus on biologics over the last 20 years has led dermatologists to think about efficacy in terms of PASI. It is fairly widely known that PASI is not very accurate when you have very low body surface areas involved. Dr. Kim Papp in Toronto pointed this out to us and he came up with his idea for the PASI-HD, where from zero to nine percent, rather than using an integer, we use a fraction. This enables us to measure a change from nine percent to one percent BSA.

“We helped develop and validate PASI-HD to give doctors a more accurate picture of what’s happening in low BSA subjects, which are the vast majority of psoriasis patients. Probably 75 percent of psoriasis patients have less than 10 percent BSA on their whole body.”

New Developments are Anticipated

“In the next year, hopefully we’ll launch roflumilast cream for psoriasis. Then we should have readouts from our Phase 3 studies in atopic dermatitis, seborrheic dermatitis, and scalp psoriasis, with the latter two studies investigating our foam formulation of roflumilast.

“Our guiding principle is that dermatology patients deserve better options than what they have currently. I’m confident with the team that we’ve put together, that there’s going to be a steady stream of innovative new products coming. By that, I mean innovation that solves a real problem for a doctor or a patient.”