MedicalResearch.com Interview with:
Luis Squiquera, MD
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Squiquera: Ranpirnase is a small peptide that has a characteristic enzymatic activity against double stranded RNA (dsRNA). As a drug it has been extensively tested intravenously in high concentration for oncology in over 1000 patients with different types of malignancy, especially mesothelioma, with minimal side effects and mainly a transient increase of serum creatinine level observed.
In the last year we started a comprehensive antiviral program and obtained encouraging results in several RNA and DNA virus families. Several research groups have already studied the anti HIV activity. HPV was one of many viruses that showed a high selectivity index in our antiviral screening (the relationship between efficacy and cytotoxicity). We were encouraged by the low concentrations (nanomolar range) needed to stop virus reproduction in cell cultures. We performed in vitro analysis of two of the main HPV types that cause human disease (HPV 11 and 16). HPV 11 was highly sensitive to ranpirnase; and since this is one of the main virus type responsible for inducing genital warts, we decided to focus our efforts in bringing the drug to a new route of administration.
We set out to obtain and did obtain a formulation that was extremely stable, even at high temperatures. Before using it in patients, we performed testing for irritation using standardized Draize animal models. Even though we ran these tests in high concentrations (1 mg/ml) the final product was not irritant and was deemed safe to use in a clinical setting.
With these safety data on hand – plus extensive experience in IV dosing and non-irritation in animal models – we decided to make the formulation available as a compassionate use for patients with genital warts.
As we reported in our presentation in San Francisco, all cases that completed an 8-week treatment showed clearance of the lesions. Some of the cases were cleared in as soon as two weeks and the average time for clearance was 33 days. One of the patients had to be discontinued due to an eczematous skin reaction. We will be studying the characteristic of this effect in our trials.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Squiquera: Even though we are in early stages of development, the use of an antiviral to treat warts is a completely new approach. Our initial results are very encouraging but there are many issues to be optimized including the right concentration and dosing schedules. We also need to study the antiviral effect with several other types of HPV. We were asked whether we knew the effect of this formulation on high risk HPV such as the ones involved in squamous cell carcinoma – this effect needs to be studied.
We are ready to start a phase I/II clinical trial and are finishing details for a larger proof of concept study to be conducted in Colombia and/or Mexico. In addition, we are looking to study ranpiranse as a preventive treatment for viral infections in the US. A proof of concept study will give us information on how ranpirnase performs against other drugs in the market. So far we can only compare the clinical performance with published results but we need direct input from large clinical trials.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Squiquera: We have a drug that has interesting characteristics, it has a very strong antiviral effect and induces cell death of transformed cells while being non-toxic for normal cells. All of these mechanisms interplay in the effect against HPV. We know that HPV interferes with the cell cycle and that this is the cause of unchecked cell division observed in warts.
This is an initial and important step in a drug that can deal with the basic mechanisms involved in the pathogenesis of warts.
HPV is widely prevalent, with about 50% of sexually active individuals coming in contact with this virus, causing a high degree of morbidity and interfering enormously in the lives of the patients.
We are postulating a more rational approach to treatment of warts rather than the elimination of the visible lesions, which is the current standard of care. We know that there is a lot of work to be done but we are confident that we could be a leading case in the development of effective anti HPV treatments.
American Academy of Dermatology
The study of ranpirnase was supported by Tamir Biotechnology.
Squiquera is an employee of Tamir Biotechnology
MedicalResearch.com Interview with: Luis Squiquera, MD (2015). First Antiviral Medication For HPV Infections Shows Promise