Pharmaceutical Technology

Lutris wins FDA orphan drug tag for EGFR inhibitor-induced rash candidate

LUT014 is being investigated in an ongoing Phase II trial as a first-line treatment for EGFR inhibitor-induced acneiform rash, for which there is no approved drug.

Lutris Pharma has secured a US Food and Drug Administration (FDA) orphan drug designation for its BRAF inhibitor LUT014, an investigational treatment for epidermal growth factor receptor (EGFR) inhibitor-induced acneiform rash.

EGFR inhibitors are used as cancer treatments, however dermatological side effects such as acneiform lesions, a skin condition that appears as small red bumps or pustules on the skin, seen with the treatment affect a patient’s quality of life.

Approximately 75% of cancer patients taking EGFR inhibitors develop some form of an acneiform rash, according to Lutris’ CEO Noa Shelach.

The candidate is currently being investigated in a Phase II clinical trial (NCT04759664), where 117 colorectal cancer patients with acneiform lesions receive either one of two strengths of LUT014 gel once a day for four weeks, or a placebo.

EGFR, found on cell surfaces including skin, regulates crucial cell functions such as growth and differentiation. It is overexpressed in cancer cells, so EGFR inhibitors prevent cancer cells from receiving the signals needed for growth and division, inhibiting tumour growth and progression.

LUT014 is a BRAF inhibitor that is applied topically on the skin. BRAF, a protein translated from the BRA gene, is part of the EGFR signalling pathway. LUT014 helps to shrink tumours with mutated BRAF proteins while promoting cell growth in normal cells, helpful for conditions such as an acneiform rash.

In the announcement accompanying the orphan drug designation, Shelach said: “Receipt of orphan drug designation for LUT014 is strategically important for Lutris, as it reflects the significant unmet need for patients treated with EGFR inhibitors.

“The [orphan drug designation] also qualifies us for incentives including tax credits for qualified clinical trials, exemption from user fees and potentially seven years of marketing exclusivity for LUT014, should it gain approval for the treatment of EGFRI inhibitor acneiform rash.”

In March 2023, the FDA approved Novartis’ Tafinlar and Mekinist BRAF/MEK inhibitor combination therapy to treat BRAF V600E low-grade glioma in paediatric patients starting at one year of age. Findings from the Phase II/III TADPOLE trial listed acneiform rash as one of the most common adverse reactions observed.