Please provide information on all virotherapy applications and drugs currently available or being researched.

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Please provide information on all virotherapy applications and drugs currently available or being researched.

Hello! Thanks for asking Wonder about all virotherapy applications and drugs currently available or being researched. The short version of the answer is that T-Vec, Enadenotucirev and Rigvir are the main virotherapy products being researched on or available in the market. There are, however, many other related researches and products in across the world, including (but not limited to): Telomelysin, Pexa-Vec, Gendicine, and Oncorine. On a different note, global virotherapy drugs and research is led by Asia, USA and UK, respectively, in terms of regions. Kindly find below a brief highlight of the methodology I used to arrive find my answers, followed by a deep dive of the findings.

METHODOLOGY
In my research, I took note of your resourceful comments and began my studies by preliminarily looking into any available information with regards to T-Vec and Rigvir. I then went on further to search for supplemental information from authoritative sites on other virotherapy studies and drugs in the US, Asia, UK and pretty much every continent so as to provide a comprehensive response to your question. It is based on this expansive global research that I was able to complete the report that is detailed below. Needless to say, there might be a few drugs and applications that I may have humanly missed, but I did ensure that my research was as thorough as possible in order for me to give you an all-inclusive representation of the global virotherapy picture. With that being said, let’s get to the findings.

T-VEC
Formerly known as OncoVexGM-CSF, T-Vec is a biopharmaceutical drug that is injected directly into patients with melanoma lesions that cannot be surgically removed. Once a patient’s immune system has been activated by the T-VEC treatment (which is often administered in a dose every two weeks for up to 18 months), the system reportedly develops an enhanced ability to detect and attack cancer throughout the body. T-Vec was first approved by the US FDA to treat melanoma, and this was followed by an approval by the EMA in December 2015—making it the first approval of an oncolytic virus in the West. There have been no clear-cut proofs that T-Vec helps to extend the life of people with melanoma, or even that the drug prevents metastasis. However, recent studies indicate that there have been significant results to support the use of T-Vec for patients with aggressive melanoma.

For example, in study that was led by Kevin Harrington, a professor of biological cancer therapies at the Institute of Cancer Research London; dosages of T-Vec were administered on over 400 patients with aggressive melanoma. From this trial, “1 in 4 patients responded to the treatment, and 16% were still in remission after 6 months.” The trial further reported that “10% of the patients treated had complete remission,” showing no detectable signs of cancer. Moreover, patients from the study that had stage 3 and early stage 4 melanoma lived an average of 41 months. Compared to the average survival rate of 21.5 months in the 66 earlier-stage patients who received T-Vec, it's no wonder that this control treatment warrants all the attention it gets as one of the major virotherapy applications in the market.

RIGVIR
Rigvir is an active immunotherapy in cancer treatment that works on the premise of using a virus to find and destroy malignant cells in the human body. Rigvir was first registered for melanoma treatment in Latvia in 2004, and has since been used treat approximately 75 percent of melanoma patients. Unlike most standard treatments for cancer that offer low survival rates, Rigvir has helped to offer a much better outlook in terms of better life quality and a higher survival rate, especially as a virotherapy for late stages cancer patients such as stage IV M1c, histiocytic sarcoma stage IV and small cell lung cancer stage IIIA. Reportedly, “cancer patients described [with Rigvir] were diagnosed 3.5, 7 and 6.6 years ago and their conditions have improved and have been stable for over 1.5, 6.5 and 4 years, respectively.” These encouraging observations point to the increasingly popular belief that oncolytic virotherapy using Rigvir can successfully be used in long-term treatment of late-stage cancer patients.

ENADENOTUCIREV
Enadenotucirev is a recently discovered anti-cancer therapeutic that targets cancerous tumors in the, breast, colon, lung, pancreas and bladder and lung. This vaccine—which is “administered in combination with nivolumab in subjects with metastatic or advanced epithelial tumors (with focus on CRC, UCC, SCCHN and salivary gland cancer)”—was first tested in 2015 in a clinical trial by PsiOxUs Therapeutics, a research institute in the UK. It has since been administered to quite a number of patients in the UK, particularly those not responding to standard therapy. A complete report of the findings from Phase I of the clinical trial by PsiOxUs Therapeutics is exhaustively detailed here.

TELOMELYSIN (OBP-301)
Oncolys, a Tokyo-based company, has been seeking approval for a Phase II trial of a drug called Telomelysin (OBP-301) in subjects with advanced melanoma that can’t be treated using surgery. This treatment is essentially designed to be injected directly into tumors like T-Vec, and then in turn infecting and killing malignant cells while also helping to stimulate the release of antigens that direct immune responses to the cancerous cells. The modified viruses that are injected on the patients are engineered to replicate only in cancer cells, hence leaving healthy cells intact. Oncolys has already set up a Japan-US subsidiary to help spearhead the necessary partnerships and developments in regards to the testing of Telomelysin. The Japanese company says it will strongly push for trials and applications of the therapy in Japan and US if its first Phase II trial comes up positive.

OBP-301 AND OBP-702
Two types of telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and OBP-702, both armed with the wild-type p53 tumor suppressor gene have been heavily undergoing research in Japan as options for oncolytic viruses. These studies are largely based on the antitumor effect of OBP-301 and OBP-702 in human colorectal cancer cells using XTT assay. Further reports indicate that Denka Seiken, a Japanese company, has decided to construct its first production facility for a virus-based anticancer drug that will be used in oncolytic virotherapy. This virotherapy will be using “a genetically-modified herpes simplex virus type-1, and the biological drug incorporating it is expected to represent an epoch-making advance as a cancer treatment that leverages the properties of the virus.” An investigative clinical trial has been going on since 2015 to help ascertain the efficiency of this latter viral therapy application from Denka Seiken.

PEXA-VEC
Formerly known as Jennerex, JX-594, Pexa-Vec is a therapy that aims at patients with advanced hepatocellular carcinoma who have failed locoregional therapies and are medically eligible for treatment with sorafenib. SillaJen, an oncolytic immunotherapeutics company with headquarters in South Korea, recently announced that an American patient has been enrolled in an ongoing multinational randomized phase III open-label study of Pexa-Vec. Going under the code name “the PHOCUS trial”, this multinational study “is designed to enroll 600 patients who have not received prior systemic treatment for their cancer, who will be randomised to sorafenib with or without Pexa-Vec.” According to SillaJen, this will be conducted at approximately 140 sites across the world, including Asia, Australia, North America and Europe.

GENDICINE
Notably, the first viral immunotherapy in China was approved 10 years ago, and it was a cold virus engineered to treat head and neck cancer. China soon became a haven for cancer patients after that with a lot of people from across the world visiting the country for a variety of viral cancer remedies. Gendecine, a recently approved drug in China for head and neck squamous cell carcinoma (HNSCC), is one of the drugs that is a direct beneficiary of the long-standing studies and trials on virotherapy in China. Essentially, Gendicine “is a replication-incompetent, recombinant, serotype 5 human adenovirus engineered to contain the human wild-type p53 tumor-suppressor gene.”

ONCORINE
This is another virotherapy that is legally approved for use in China. Oncolytic virotherapy, which is commonly known as Oncorine for HNSCC, is a classic (replication competent) Ad5 with an E1B and E3 gene deletion that is reported to help in control of cancer cells.

SENSITIZER
A small molecule known as the sensitizer has been discovered as a new way to deal with cancer cell defenses, according to a group of Canadian researchers. Based on the results from the research, the addition of the sensitizer may be the key to ensuring OV success, with the study revealing that cancer progression had slowed down courtesy of the small molecule. This discovery suggests that the addition of a small molecule could one day end up making OV a true cancer cure.

AFTERWORD ON VIROTHERAPY AND CANCER
Evidently, a lot of progress has been made in the medical world regarding virotherapy applications and drugs currently available or being researched. T-Vec and Rigvir are most popular, but the rest of the viral therapies (both in the form of drugs and research) are gaining a lot of traction, including Enadenotucirev, Telomelysin, Pexa-Vec, Gendicine, Oncorine, OBP-301 AND OBP-702, and Sensitizer. On another note, Asia and USA lead the rest of the world in terms of virotherapy research and products, followed by the UK. Even so, more research, funding and investments are required if permanent solutions are to be found in the field of virotherapy as the go-to option for curbing the global cancer pandemic. I hope this answers your question and serves the purpose you have for it. Otherwise, thanks for using Wonder; hope we can be of assistance to you once again soon.
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