FDA Approves First in a New Class of Immunotherapies

After much deliberation, the FDA today approved a new type of immunotherapy for the treatment of advanced melanoma. Called talimogene laherparepvec (T-VEC, trade name Imlygic™), and made by Amgen, the immunotherapy is an oncolytic virus therapy. This is a genetically engineered virus that has been tweaked to preferentially kill cancer cells. In the case of T-VEC, the virus is a modified version of the herpes simplex virus I, the virus that causes cold sores.

The approval of T-VEC comes six months after an independent advisory panel voted 22-1 to recommend approval of the therapy. Initially, the FDA had appeared unlikely to approve T-VEC, based on questions about which patients would definitely benefit, but the recommendations of the advisory panel apparently helped to change some influential minds.

“There are clearly patients in my clinic I’d like to use this for,” said Patrick Hwu, MD, of MD Anderson Cancer Center and the advisory panel, who voted in support of T-VEC.

The FDA’s approval was based on results from a phase III trial that included 436 patients with inoperable stage III and IV melanoma. Patients were randomized to receive either T-VEC or another immune-stimulating drug called GM-CSF. The primary endpoint of the study was durable response rate (DRR), meaning the percentage of patients who experienced an ongoing benefit from the treatment. The DRR for patients receiving T-VEC was 16.3% versus 2.1% for those getting GM-CSF. The trial’s secondary endpoint, improvement in overall survival, was not met, although there was a trend in the direction of improved survival for patients receiving T-VEC.

Oncolytic viruses kill cancer in two ways: first, they preferentially infect and replicate inside cancer cells, causing them to burst, or lyse. Then, they act as a kind of vaccine, releasing a payload of cancer antigens that are taken up by cells of the immune system, which is prodded into mounting a body-wide attack against cancer cells bearing those same antigens. T-VEC also contains a gene for an immune-boosting molecule called GM-CSF that aids in this process.

Watch an animated video below that explains how oncolytic virus therapy works:

As of today, T-VEC is approved as solo treatment of advanced melanoma that has relapsed after surgery and is inoperable. The immunotherapy is administered as an injection directly into tumor sites. Side effects are usually mild, and most commonly include fatigue, fever, chills, nausea, and pain at the injection site. Because T-VEC is made from a live herpes virus, herpes virus infection is also a possible side effect.

T-VEC may help some patients who have localized disease in the skin or lymph nodes, or who have not responded to other therapies such as checkpoint inhibitors. In addition, T-VEC is currently being tested in several different clinical trials that combine the virus therapy with other immunotherapy drugs. It may be as part of such combination regimens that T-VEC will have its greatest impact on patients.

Despite the impressive, cure-like responses that some patients have experienced with individual immunotherapies, not everyone responds in the same way. The challenge in the field now is to increase the percentage of people who respond. Many experts argue that the best way to boost responses is to combine several agents that work in complementary fashion, each targeting a different part of the multi-step immune response. By releasing cancer antigens, T-VEC may act at the very beginning of an immune response, helping to jumpstart it into action. Other drugs that “take the brakes off” the immune response may help to keep that response chugging along for long enough to successfully kill the cancer everywhere it is hiding in the body.

Through its Clinical Accelerator, the Cancer Research Institute is leading efforts to conduct innovative clinical trials of promising combinations of immunotherapies, including oncolytic viruses.