FDX104 for Chemotherapy-Induced Rash

FDX104 for Chemotherapy-Induced Rash

Foamix is developing FDX104, a doxycycline foam product candidate for the treatment of acne-like rash, induced by Epidermal Growth Factor Receptor Inhibitors (EGFRI) drugs. 
  
Acne-like rashes are commonplace in patients undergoing chemotherapy
 
Between 45% and 100% of cancer patients taking Epidermal Growth Factor Receptor Inhibitors (EGFRIs), such as cetuximab (Erbitux®, Eli Lilly) or panitumumab (Vectibix®, Amgen), are affected by severe acne-like rashes on the face and upper trunk. These rashes can be associated with pain, itching, and infections.  These symptoms can create compliance issues, and lead to patients modifying their dosages of EGFRI drugs or discontinuing treatment completely.
 
While there are no approved treatments for EGFRI-induced rash, oral doxycycline and minocycline are currently used ‘off-label’ to treat patients with this condition. Though oral antibiotics are often considered the standard of care, there can be significant drawbacks with these therapies, including systemic side effects and potential drug-drug interaction with EGFRI products. 

Using our proprietary technology, we developed a stable topical formulation of doxycycline (FDX104).  Doxycycline has pharmacologic attributes and physicochemical characteristics similar to minocycline. 
 
Positive results in Phase II clinical trial 
 
Twenty-four patients were enrolled and received study drug in a multicenter, randomized, double-blind, placebo-controlled, Phase 2 clinical study to evaluate the safety and efficacy of FDX104.  Each patient acted as his or hers own control by treating one side of the face with FDX104 and the other side with the matching foam vehicle (Placebo) in a blinded and randomized manner. Photographs of the front and each side of the face were taken at each study visit; these photographs were used for blinded grading of rash severity by an independent dermatologist at the end of the study.  The ratings of rash severity were:  None=0, Mild=1, Moderate=2 and Severe=3, as described by Scope et al.(3)  The key findings were:
  • In the entire study population (N=24) the severity of rash on the FDX104 treatment side of the face was overall better than in the Placebo-treated side.
  • The mean Maximal rash severity (N=24) was 1.33 and 1.71 in the FDX104- and placebo-treated sides respectively.
  • Nine of the 24 patients in the study (37.5%) developed severe (Grade 3) rash during the study on the placebo-treated side, while only 4 of the 24 patients in the study (16.7%) developed severe rash on the FDX104-treated side.
  • Comparison of the two treatments on the prevention of severe rash reached statistical significance (p<0.05, Wilcoxon Signed-Rank test). Various other exploratory analyses trended similarly.
  • FDX104 appears safe and well-tolerated.  No drug-related systemic adverse events were recorded.  Local reactions were noted in 6 patients, all were mild and 5 were resolved before the end of the study.