Advancements in Skin Rash Prevention: The Role of OQL025 Topical Cream in Mitigating EGFR Inhibitor-Induced Dermatological Reactions

Epidermal growth factor and its receptor are found in various cells, including skin cells, and play a role in skin healing by promoting cell growth. However, mutations in the receptor can lead to cancer. Inhibitors targeting this receptor are used to treat certain cancers but can cause skin inflammation. A new topical cream formulation, OQL025, which contains a prodrug OQRC184 that releases a JAK inhibitor tofacitinib, is being tested to prevent this skin reaction.

The prodrug is formulated to improve its ability to penetrate the skin and release the active ingredient into the tissue. The potency of OQRC184 and tofacitinib on JAK enzymes was tested in vitro. The absorption and distribution of the prodrug in minipigs were studied, with blood samples taken at various intervals to measure the levels of OQRC184 and tofacitinib.

A preclinical study in rats was conducted using the cream to prevent skin reactions caused by EGFR inhibitors. The rats were divided into groups, some receiving the cream with different concentrations of OQRC184 and others a control cream, while all were exposed to a medication causing skin rash.

The results showed that OQRC184 had significantly less inhibitory activity against JAK enzymes compared to tofacitinib. After application, the plasma levels of both the prodrug and the active ingredient were found to be low. The incidence of severe skin rash was reduced in rats treated with the cream, especially with the higher concentration of OQRC184. The average severity of the rash in the treated groups was significantly lower than in the control group.

In conclusion, the prodrug OQRC184, designed to release tofacitinib into the skin, showed minimal systemic exposure and was effective in reducing skin reactions caused by EGFR inhibitors in the tested models.