New Atopic Dermatitis Drugs Show Promise, But Safety Concerns Emerge Over Kaposi Sarcoma Risk
Three leading dermatologists recently gathered for a virtual roundtable discussion about atopic dermatitis (AD), the most common form of eczema. The conversation, which took place after the American Academy of Dermatology (AAD) annual meeting, focused on the safety of a new class of treatments called OX40-targeted therapies.
The panel included moderator Dr. Peter A. Lio from Northwestern University Feinberg School of Medicine in Chicago, Dr. Sarina B. Elmariah from the UCSF Center for Itch and Neurosensory Disorders in San Francisco, and Dr. Jennifer Soung, a dermatologist and director of clinical research at Southern California Dermatology in Orange County.
The main topic was the safety signal surrounding OX40-targeted drugs after cases of Kaposi sarcoma (KS) appeared during clinical trials. Kaposi sarcoma is a rare type of cancer that affects the skin and other organs. One drug in this class, rocatinlimab, an OX40 blocker, has already been dropped from development. Another drug, amlitelimab, also showed KS cases in its program.
Dr. Soung shared her firsthand experience as an investigator in these trials. She noted that her patients showed real improvement, and the late-breaking data presented at the AAD meeting confirmed what she saw in her clinic. One key finding: the treatment responses had not yet peaked at the six-month mark. This means patients might continue to get better over time. Dr. Soung expressed hope that this next generation of biologics could deliver faster and deeper results — meaning clearer skin and near-zero or minimal itch.
However, Dr. Soung also voiced caution. She explained that OX40 targets T cells, which are a critical part of the immune system. Because T cells play many roles in the body, blocking them could have unintended consequences. She pointed out that in phase II trials, researchers are still figuring out the best dose. Older patients who receive higher doses may need extra monitoring.
The two cases of Kaposi sarcoma — one in the amlitelimab program and one in the rocatinlimab program — came as a surprise to researchers. Dr. Soung predicted that the U.S. Food and Drug Administration (FDA) will likely require a warning label on any approved drug in this class. That could make it harder to explain the risks to patients, especially when compared to existing treatments like dupilumab (Dupixent) and lebrikizumab (Ebglyss), which have very clean safety records.
Dr. Elmariah agreed that the potential benefits of OX40-targeted therapy are real, but she emphasized that the AD patient population is very diverse. Different patients will need different treatments depending on their age, health history, and other factors. She noted that the KS cases occurred in patients who already had risk factors for the cancer. So doctors may need to be especially careful about who receives these drugs.
Still, Dr. Elmariah sees a role for these agents. She described them as offering durable control — though she hesitated to call it remission. She said that having more options allows doctors to tailor treatment to each patient’s specific needs.
Dr. Soung added that clinical trials are teaching researchers more about the disease itself. For example, nemolizumab (Nemluvio) targets interleukin-31 (IL-31), a molecule involved in itch. The drug is very effective at stopping itch, but it does not clear skin lesions as well. Dr. Soung admitted she had assumed that breaking the itch-scratch cycle would allow eczema lesions to heal on their own, but the data showed otherwise.
On the topic of remission, Dr. Soung referenced a lebrikizumab study. In that trial, patients who achieved clear or almost-clear skin (measured as a Psoriasis Area and Severity Index [PASI]-75 or an Investigator Global Assessment [IGA] score of 0 or 1) at week 16 were taken off the drug. About 40% to half of those patients maintained their response for a period of time without treatment. This suggests that some drugs may offer lasting benefits, possibly even disease modification. A recent study from last fall found that lebrikizumab could potentially be dosed every eight weeks, further supporting the idea of long-lasting control.
The panel concluded that while OX40-targeted therapies hold promise, the safety concerns — especially the Kaposi sarcoma risk — mean doctors and patients will need to weigh the benefits carefully. If approved, these drugs may be best suited for patients who have not responded well to other treatments and who do not have risk factors for KS. As always, more research will help clarify who benefits most and how to minimize risks.
Source: MedPage Today
