IN BRIEF

A Watershed Moment for Cancer Virotherapy

May 11, 2015

A recent decision may define the future of virotherapy’s role in the clinical treatment of cancer.

At 4:50 pm on Wednesday, April 29 2015, the votes were cast: 22 in favor, 1 against. With this overwhelming majority, an advisory committee sent a clear message to the FDA recommending the first marketing approval for a live virus cancer therapy. It was a metaphorical shot in the arm for cancer patients, doctors and scientists heard around the world.

The FDA won’t make a final decision for several months, and the advisory committee’s recommendation is not binding, but this vote has been a long time coming.

Virotherapy: From Humble Beginnings

The idea of using infectious agents to infect and kill cancer cells or elicit an immune response against cancer cells first grew out of case reports from the 1800s. Back then, no anticancer, antibiotic or antiviral therapies were available, and physicians watched helplessly as some patients developed cancer and others suffered from infections like influenza. Occasionally, patients contracted both simultaneously.

As if it were a quirky experiment of nature, some of these dually affected patients were observed by their doctors to experience cancer remissions following infections. With the advent of virus and bacterial isolation at the turn of the 1900s and the subsequent discovery of tumors in rodents, the 1920s began an era of testing and confirming the idea that directly injecting tumors with infections could induce cancer regression and even remission.

In the 1940-1970s, cancer patients were injected with live viruses. Some had their tumors shrink or disappear, but they also usually suffered from rampant infections. At the same time, chemotherapy showed considerable promise, and virotherapy was all but forgotten.

Modern-Day Virotherapy

In the modern age of gene splicing, we have figured out how to cripple viruses so they no longer cause disease, but they retain their ability to infect and kill tumor cells.

Over the past 15 years, there has been an explosion of interest in cancer virotherapy, with numerous preclinical studies and clinical trials being published on a wide variety of cancer types using many different types of viruses.

Companies have also been popping up, including BioVex outside of Boston. Their virus is derived the cold sore virus, HSV1, and they’ve been injecting it into patients’ melanoma lesions in various clinical trials for about seven years. They caught the eye of Big Pharma in 2010, and the pharmaceutical giant Amgen scooped them up for a mere billion dollars.

In July 2014, Amgen submitted a Biologic License Application for their virus, called T-VEC, to the FDA. Though it took nine months for the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee and Oncologic Drugs Advisory Committee to convene, the group was sufficiently impressed with the results.

I have the pleasure of serving on the committee, and I enjoyed the debate. The data showed clear benefits, and several in-person testimonials given by melanoma survivors treated with T-VEC were compelling. The committee’s one dissenting vote was based on the fact that the virus seemed to do best in patients with lower-stage disease; that individual advocated for restricting approval only to those patients, making the vote essentially a conditional “yes.”

The Future of Virotherapy for Cancer

If the FDA follows through on the committee’s recommendation, I believe it will usher in a new era of cancer therapy.

For some patients, viruses may be a cure. For most, though, viruses will likely represent, as one committee member put it, “another arrow in the quiver” that physicians and patients can consider using on a case-by-case basis. Of course, this first approval will only be for a specific virus for a specific indication (melanoma).

Having seen glimpses at meetings and in the medical literature of the pipeline of viruses in development in labs and companies around the world, and having seen results in animal models and some early phase clinical trials, I am confident the T-VEC story is just the beginning. I believe over the next few years we will see the quiver get filled with arrows of all shapes and sizes (still in the nanometer range, though!).

We still need to figure out which viruses are best for which patients, at what doses and dose schedules and in what combinations with other therapies (surgery, radiation, chemotherapy, targeted therapy, other immunotherapies). We have some agents showing promise that need more testing, but I believe that virotherapy in 2015 is akin to chemotherapy in 1950: full of promise and sure to benefit from many future advances.

There is a lot of work ahead — both in the laboratory and in the clinic — to learn how to fully turn one human scourge (viruses) against another (cancer). For over a century, the idea has only been a dream shared by small, scattered groups of scientists and doctors as they cast around for something better for their patients. With the FDA vote, that dream took an important leap toward becoming reality.

 

Join the conversation. What do you believe to be the primary challenges still facing the field of cancer virotherapy?

 

Timothy Cripe, MD, PhD, is chief of the Division of Hematology, Oncology and Blood and Marrow Transplantation at Nationwide Children’s Hospital. His clinical interests include gene and viral therapies for solid tumors in children, including brain tumors, neuroblastoma and bone and soft tissue sarcomas. Dr. Cripe’s current research focuses on developing and testing new therapies for pediatric solid tumors and translating those findings into clinical studies. He was among the first in the country to launch clinical trials of attenuated oncolytic viruses in children.