Actinic Keratosis (AK) is a pervasive and serious pre-cancerous condition, being the third most common complaint treated by dermatologists. As a precursor of non-melanoma skin cancer, including both basal (BCC) and squamous cell carcinoma (SCC), and with nearly 1.3 million diagnoses annually in the United States; it is responsible for thousands of preventable cancer deaths. In the US, SCC is the second most common form of skin cancer, afflicting 200,000 people per year. SCC results from abnormal keratinocyte growth in the epidermis and invasion into adjacent tissues. Without curative local treatment to achieve disease-free pathological margins, SCC disseminates into subcutaneous space, draining lymph nodes, and perineural capsules. Recurrent lesions carry high risk of metastatic disease (25-45%) and significant morbidity and mortality (25% have 5-year survival). Therefore the most effective clinical management is early detection plus highly-curative initial therapy. Front-line procedures are associated with local recurrence rates of ~15%, while Mohs Microsurgery reportedly reduces this rate to ~3%. Thus, 6,000 patients per year experience local recurrence, and 1,500-3,000 harbor metastatic disease, creating a medical need for topical chemotherapy as an adjunct to initial procedures to reduce rates of local recurrence.

Several surgical and pharmaceutical treatment options are available, including retinoids, which are the synthetic and natural analogs of vitamin A. These formulations are active in several types of pre-malignant skin lesions such as keratocanthoma, xeroderma pigmentosum and epidermodysplasia verruciformis; and have been successful as topical treatments. One such analog grouping, NSAIDs, for example, has been steadily gaining importance as a chemo-preventive agent in recent years as evident by a topical diclofenac preparation (Solaraze®) which entered the US market in January 2002.  Topical products containing 5-fluorouracil are also used as treatment. However, no treatment is ideal due to undesirable side effects like unsightly pigmentation, painful erosions and inflammatory reactions, long treatment periods, and high relapse rates. For example, Efudix™ 5% is a cream of a cytotoxic anticancer agent (5-fluorouracil) that applied for several weeks often clears in situ SCC. However, its stinging and burning, and inflammatory reaction/contact dermatitis at the site of application, result in ulcers and scars. Such adverse events not only limit patient compliance, but more importantly prevent long-term maintenance therapy. Hence, there exists an explicit need for an effective and well-tolerated treatment for both BCC and SCC that will improve patient acceptability and compliance.

SciTech’s R&D goal, in this area, is to create better tolerated and more efficacious topical products based on our proprietary retinoid delivery expertise. A key element of this strategy is development of products that combine retinoid and non-retinoid therapeutic classes to achieve reduced dose regiments and improved long-term tolerability.

SciTech received product development rights for three topical formulations of an investigational anticancer drug, previously known to possess anti-inflammatory properties, developed for oral and IV therapy of solid tumors. A published clinical study of daily topical application of the oral formulation in pre-malignant actinic keratosis reported responses in all patients but no cases of inflammation, despite the sub-optimal formulation. SciTech pilot studies identified two topical formulations with physical and chemical stability of >1 year in storage. Using human epidermis, in vitro application of either cream achieved tissue levels that are known to induce cancer cell apoptosis in other models by hours, yet epidermal flux was undetectable (predicting for very low systemic absorption in man). This project studied effectiveness and human safety in an in vitro disease model, suppression of inflammatory properties common to Efudix™ when used in combination, identified a lead product, and obtained a commitment from an experienced pharmaceutical partner for manufacturing and proof-of-principle clinical trials.

Actinic Keratosis (AK) is a pervasive and serious pre-cancerous condition, being the third most common complaint treated by dermatologists. As a precursor of non-melanoma skin cancer, including both basal (BCC) and squamous cell carcinoma (SCC), and with nearly 1.3 million diagnoses annually in the United States; it is responsible for thousands of preventable cancer deaths. In the US, SCC is the second most common form of skin cancer, afflicting 200,000 people per year.

SCC results from abnormal keratinocyte growth in the epidermis and invasion into adjacent tissues. Without curative local treatment to achieve disease-free pathological margins, SCC disseminates into subcutaneous space, draining lymph nodes, and perineural capsules. Recurrent lesions carry high risk of metastatic disease (25-45%) and significant morbidity and mortality (25% have 5-year survival). Therefore the most effective clinical management is early detection plus highly-curative initial therapy.

Front-line procedures are associated with local recurrence rates of 15%, while Mohs Microsurgery reportedly reduces this rate to 3%. Thus, 6,000 patients per year experience local recurrence, and 1,500-3,000 harbor metastatic disease, creating a medical need for topical chemotherapy as an adjunct to initial procedures to reduce rates of local recurrence.

Several surgical and pharmaceutical treatment options are available, including retinoids, which are the synthetic and natural analogs of vitamin A. These formulations are active in several types of pre-malignant skin lesions such as keratocanthoma, xeroderma pigmentosum and epidermodysplasia verruciformis; and have been successful as topical treatments. One such analog grouping, NSAIDs, for example, has been steadily gaining importance as a chemo-preventive agent in recent years as evident by a topical diclofenac preparation (Solaraze®) which entered the US market in January 2002. 

Topical products containing 5-fluorouracil are also used as treatment. However, no treatment is ideal due to undesirable side effects like unsightly pigmentation, painful erosions and inflammatory reactions, long treatment periods, and high relapse rates. For example, Efudix™ 5% is a cream of a cytotoxic anticancer agent (5-fluorouracil) that applied for several weeks often clears in situ SCC. However, its stinging and burning, and inflammatory reaction/contact dermatitis at the site of application, result in ulcers and scars. Such adverse events not only limit patient compliance, but more importantly prevent long-term maintenance therapy.

Hence, there exists an explicit need for an effective and well-tolerated treatment for both BCC and SCC that will improve patient acceptability and compliance.

SciTech’s R&D goal, in this area, is to create better tolerated and more efficacious topical products based on our proprietary retinoid delivery expertise. A key element of this strategy is development of products that combine retinoid and non-retinoid therapeutic classes to achieve reduced dose regiments and improved long-term tolerability.

SciTech received product development rights for three topical formulations of an investigational anticancer drug, previously known to possess anti-inflammatory properties, developed for oral and IV therapy of solid tumors. A published clinical study of daily topical application of the oral formulation in pre-malignant actinic keratosis reported responses in all patients but no cases of inflammation, despite the sub-optimal formulation.

SciTech pilot studies identified two topical formulations with physical and chemical stability of 1 year in storage. Using human epidermis, in vitro application of either cream achieved tissue levels that are known to induce cancer cell apoptosis in other models by hours, yet epidermal flux was undetectable (predicting for very low systemic absorption in man). This project studied effectiveness and human safety in an in vitro disease model, suppression of inflammatory properties common to Efudix™ when used in combination, identified a lead product, and obtained a commitment from an experienced pharmaceutical partner for manufacturing and proof-of-principle clinical trials.