Basal cell carcinoma treatments on the horizon

June 13, 2019

In this pipeline report, Dermatology Times presents insights into Hh pathway inhibitors currently in phase 2 and phase 3 for the treatment of basal cell carcinoma. 

In this pipeline report, Dermatology Times presents insights into two drugs currently in phase 2 and phase 3 for the treatment of basal cell carcinoma. 

Basal cell carcinoma (BCC) is the most common type of human skin cancer, accounting for 80% of non-melanoma skin cancers.1 Although most BCCs are curable by surgery, locally advanced and metastatic BCC represents a clinical challenge.

BCC is driven by the aberrant activation of Hedgehog (Hh) signaling and characterized by mutations in patched or smoothened genes. Recent advances in the understanding of the Hh signaling pathway in the pathogenesis of BCC has fueled the discovery of Hh pathway inhibitors in locally advanced and metastatic BCC patients.

Below are two Hh pathway inhibitors to keep on your radar. 

1. PATIDEGIB TOPICAL GEL 2% BY PELLEPHARM
Patidegib is an investigational topical treatment designed to mitigate the tumor burden in patients with Gorlin Syndrome and Basal Cell Carcinomas (BCCs). It is an inhibitor of the Hedgehog (Hh) pathway that binds to and inhibits the cell membrane-spanning G-protein coupled receptor SMO, which results in the suppression of Hh pathway signaling and a decrease in tumor cell proliferation and survival. 1,2,4

A phase 2, double-blind, placebo-controlled, randomized, clinical trial evaluated a patidegib topical therapy. Seventeen patients participated in the trial and were self-treated with topical patidegib for six months. There was a statistically significant difference in complete response between treatment and vehicle groups in the per protocol analysis with complete response demonstrated in 12 tumors across both treatment arms compared with zero tumors in the vehicle arm.

Other study results:

  • Complete responses were correlated with a meaningful reduction of a biomarker for hedgehog signaling (GLI1).

  • Partial responses were also demonstrated in both treatment groups.

  • Importantly, there were zero detectable levels of patidegib in plasma after topical application of patidegib gel.

  • Patients treated with this topical gel had none of the devastating class-specific systemic side effects observed with oral hedgehog inhibitors.

A phase 3 multicenter, randomized, double-blind, vehicle-controlled, efficacy and safety study in patients with basal cell nevus syndrome began in February of 2019 and will enroll 150 patients with an estimated completion of May 2020.3

Patidegib is the first topical Hedgehog inhibitor to be developed.

2. SUBA-ITRACONAZOLE BY HEDGEPATH PHARMACEUTICALS AND MAYNE PHARMA
SUBA (super bioavailability) technology is designed to improve the bioavability of orally administered drugs that are poorly soluble, such as itraconazole. SUBA-itraconazole is a patented oral formulation developed by Mayne Pharma, which is characterized by improved absorption and reduced variability compared with generic itraconazole and a more predictable clinical response.

Itraconazole is a Hedgehog (Hh) pathway inhibitor that is distinct from its anti-fungal action.2,5 A Phase 2b, multi-center, open-label study of oral SUBA-itraconazole (SUBA-Cap) in subjects with Basal Cell Carcinoma Nevus Syndrome (BCCNS) and non-metastatic BCC was initiated. The study will include 38 patients treated with 300mg daily until disease progression.6

Interim results of 13 patients and 167 analyzed lesions demonstrated:

  • 25% of the lesions disappeared.

  • 25% were reduced by more than 30%.

  • 42% were stable and 8% increased by more than 20%. 

  • No grade 2 or higher toxicities were reported for 90% of enrolled patients.7

SUBA-Cap appears to be a potential alternative to the repeated surgeries and associated scarring that characterizes BCCNS.

References:

The data from this article were compiled from the Pharmaceutical Research and Manufacturers of America 2018 Medicines in Development for Cancer Report; NIH www.clinicaltrials.gov; corporate websites, and Pubmed.

1. Tay E, et al. Hedgehog Pathway Inhibitors and Their Utility in Basal Cell Carcinoma: A Comprehensive Review of Current Evidence. Dermatol Ther 2019;9:33-49.

2. Peer E, et al. Next-Generation Hedgehog/GLI Pathway Inhibitors for Cancer Therapy. Cancers 2019,11;538:1-20.

3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). NCT03703310. Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal CellCarcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome. Avialable: https://clinicaltrials.gov/ct2/show/NCT03703310. Updated May 9, 2019.

4. Pellepharm.com

5. Hedgepathpharma.com

6. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). NCT02354261 Open-label Trial of SUBA-Itraconazole (SUBA-Cap) in Subjects With Basal Cell Carcinoma Nevus Syndrome (BCCNS). Available: https://clinicaltrials.gov/ct2/show/NCT02354261. Updated February 22, 2019.

7. HedgePath Pharmaceuticals announces positive interim data in its phase 2b cancer trial. PR Newswire. http://prnewswire.com/news-releases/hedgepath-pharmaceuticals-announces -positive-int4rim-data-in-its-phaseiib-cancer-trial-300308347.html. Updated August 3,2016.

download issueDownload Issue : Dermatology Times, June 2019 (Vol. 40, No. 6)