Relief in sight with FDX104?

REHOVOT, Israel & BRIDGEWATER, N.J.—Clinical-stage specialty pharmaceutical company Foamix Pharmaceuticals Ltd. closed the year with the release of top-line results from its Phase 2 clinical study of FDX104, a topical foam containing 4 percent doxycycline. The compound is being advanced for the prevention of moderate-to-severe skin rashes in patients treated with epidermal growth factor receptor antibody inhibitors (EGFRI) cetuximab (also known as Erbitux, marketed by Eli Lilly) or panitumumab (Vectibix, marketed by Amgen) for head and neck and colon cancers, among others.

 

EGFR is often overexpressed or dysregulated in several types of solid tumors, including gastrointestinal tumors, and therapeutics targeting the EGFR-mediated signaling pathway are becoming a leading tactic for treating advanced lung, head and neck and colorectal carcinoma. However, even though EGFR inhibitors have been shown to be effective in treating a variety of cancers, the most common side effects, occurring in between 49 and 95 percent of patients, are severe acne-like rashes on the face and upper trunk.

 

So far, there are no approved treatments for this issue, also known as acneiform rash, though some benefit has been seen through treatment with minocycline and doxycycline, as well as topical therapies. These can also result in systemic side effects, however, and potential drug-drug interaction with the primary oncology treatment.

 

“Acneiform rash is the most noticeable side effect of EGFRI drugs. In many cases, it is necessary to interrupt treatment to manage these side effects,” said Dr. Einat Shacham-Shmueli, head of the Gastrointestinal Oncology Unit at the Sheba Medical Center in Israel and a principal investigator in the study. “The ability of FDX104 to reduce the incidence and severity of such rash is impressive and promising. We currently don’t have an effective treatment for this side effect, which is especially disturbing and disruptive to this population.”

 

This study, consisting of 24 patients, focused on assessing the safety and efficacy of FDX104. The patients acted as their own control, treating one side of their face with FDX104 and the other with the matching foam vehicle (placebo). The results demonstrated a statistically significant effect of the foam in reducing the severity of the acneiform rash, with the FDX104-treated side displaying a lower severity of the rash than the placebo-treated side. Severity was assessed in two ways: one, photos were taken at each study visit for an independent dermatologist to grade at the end of the study; and two, study investigators assessed severity using a modified MASCC EGFR Inhibitor Papulopustular Eruption Grading Scale. The foam appeared to be safe and well tolerated, with no drug-related systemic adverse events. While local reactions presented in six patients, all six cases were mild, and five resolved before the end of the study.

 

“There is a significant unmet need for a safe and effective treatment for EGFRI-induced rash, and we are pleased with the results of this clinical study,” Dr. Dov Tamarkin, CEO of Foamix, commented in a press release. “FDX104 has the potential to improve patients’ quality of life and help maintain patients on their optimal anti-cancer treatment. We are dedicated to developing best-in-class medicines that can have a positive impact on patients’ lives.”

 

Brian Orelli of The Motley Fool remarked that the next step for FDX104 will likely consist of a Phase 3 program before it will secure regulatory approval, noting that “Like all small Phase 2 trials, the biggest risk is that the efficacy difference between FDX104 and placebo isn’t seen in a larger trial.” He adds that there is a potential for side effects to be identified in a larger patient population, but pointed out that FDX104’s active ingredient, doxycycline, “is a common antibiotic that’s sometime use as an oral off-label treatment for the rash, so it’s probably a low risk.”

“Investors in Eli Lilly and Amgen should keep an eye on the development of FDX104, because the companies will obviously benefit if FDX104 can help keep patients on their drug longer,” he concluded.