Frantz Viral Therapeutics is on a mission to change the landscape of care for patients with human papilloma virus (HPV)-induced pre-cancers.  Patients diagnosed with these conditions are typically treated surgically, or with off-label topicals.  There are no approved medicinal therapies available on the US market, even though surgical treatments can carry serious physical side effects, may not always be effective, and can have high recurrence rates.

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HPV is the primary cause of cancer in many parts of the body, including the cervix, anus, and vulva.  Over time, cells infected with oncogenic high-risk strains of HPV can develop into pre-cancerous lesions, and eventually into cancers.  FVT is focused on treating pre-cancerous intraepithelial lesions grades 2 and 3, also known as high grade squamous intraepithelial lesions (HSIL).  Approximately 1 million people in the US are affected by these lesions each year, and the cost to treat them exceeds $1 billion.  Even though HPV vaccines are now available, vaccination rates in the US are < 60% and there is evidence that the vaccines may not be 100% effective.  As such, there will still be a need to treat these pre-cancerous conditions into the future.

 

Some of the main complications caused by surgical treatments include potential infertility and pregnancy issues for cervical HSIL, pain and stenosis for anal HSIL, and scarring/disfigurement and pain for vulvar HSIL.  Clearly better alternatives are needed to treat these patients.  In fact, a Director at the NCI has told FVT: “The availability of a well-tolerated, non-surgical treatment option for persons with HPV-related precancer and persistent HPV infection holds tremendous potential for changing the landscape of care for these conditions, both in the US and globally.”   This is where research at Georgetown University comes into play.

 

Dr. Richard Schlegel and his research team at Georgetown discovered that artemisinin compounds were cytotoxic to papillomavirus-expressing epithelial cells (1).  The authors’ research showed that HPV infection causes cells to increase their intracellular iron levels. When artemisinin compounds interact with these cells, the oxygen bridge in the artemisinin molecule is disrupted and an oxidative reaction takes place leading to cell death through the mitochondrial caspase pathway. As healthy cells have lower concentrations of iron, they are less susceptible to these oxidative effects.

 

FVT has licensed the patents from Georgetown to use artemisinin compounds against these HPV pre-cancers.  FVT launched three open label Phase 1/2A clinical trials studying topical artesunate as a treatment for cervical, anal, and vulvar HSIL.  These studies were carried out at prestigious medical institutions, including MD Anderson, Johns Hopkins and Cleveland Clinic, and all three studies have been published in leading peer-reviewed journals.  The rate of complete histologic regression (i.e. disappearance of the pre-cancerous lesions) was reported to be 19/28 (68%) in the cervical HSIL study. As artesunate targets the infected cells, the primary focus for treatment efficacy is the regression of the pre-cancerous lesions.  The rate of clearance of detectable HPV (i.e. resolution of the infection) was 9/19 in histologic regressors (47.4%) (2).  Clearance of the HPV infections appears to be a secondary benefit of artesunate treatment.  In the anal HSIL study, a total of 10/17 (59%) subjects had either complete (6/17, 35%) or partial (4/17, 24%) histologic response following treatment with artesunate.  Half of the complete responders also had undetectable HPV following treatment with artesunate (3).  Finally, in the vulvar study a total of 12/15 (80%) responders, 8/15 (53.3%) treated subjects underwent complete histologic regression, and 4/15 (26.7%) had a partial response.  HPV clearance was reported in 5/8 (62.5%) of those with complete histologic regression (4).  No serious adverse events were reported in any of the studies.  An important benefit for artesunate treatment is that it does not preclude surgery later on if the treatment is not successful.  Therefore, there is little to no risk to the patients in using artesunate first if they wish to avoid surgery.