You know the drill. Your nose starts running, you start coughing and sneezing, and suddenly you're in the grip of a nasty cold. To rub salt in the wound, all that big-time misery is from a tiny invader -- a living thing called a virus. You know exactly what it feels like.
But have you ever realized that same virus could be harnessed to kill cancer? In fact, that's exactly what is happening in Canada. In a clinical trial funded by the National Cancer Institute of Canada, a common cold virus, AdMA3, and a virus isolated in Brazilian sandflies (perhaps even more odd) are being used to directly kill cancer and stimulate the patient's immune system.
The study is in very early stages, but other virus-based therapies that are further along have shown extremely promising results. Research institutions, such as the Mayo Clinic Cancer Center, are harnessing diverse viruses -- measles, polio, and vaccinia (cowpox) virus -- to treat a wide variety of cancers. The results are creating quite a stir in oncology circles because these treatments have incredible potential in treating metastatic cancers otherwise considered untreatable.
Making a deal with the devil
Viruses make the ideal therapeutic agent to target cancer on the molecular level because they're such precise and efficient killing machines. In fact, since way back in the 1800s, physicians have noticed that some viruses have a natural ability to kill cancer cells. Even today, there are sporadic reports of cancer patients making remarkable recoveries after viral infections. But therapeutic viruses, called oncolytic viruses, didn't start breaking out until recently, thanks to advances in the field of genetic engineering.
Genetic engineering is being widely used to modify the body's own cells to target malignant ones. But scientists have also discovered they can manipulate viral genes. By doing so, viruses can be turned into supercharged cancer killers that attack tumors directly and then signal the immune system to come in and mop up the residue.
While early stage work focused on stand-alone treatments, that approach faced significant challenges since the body's natural defenses rapidly weakened viral agents. Today, most researchers working in the field of oncolytic viruses believe their greatest potential may be in combination with other types of immunotherapy, such as checkpoint inhibitors, which work by blocking certain proteins that prevent the immune system from attacking cancer.
One combo that's particularly intriguing comes from the world's largest biotech, Amgen (NASDAQ:AMGN). The biotech is combining its virus-based therapy, called T-Vec, with Merck's (NYSE:MRK) Keytruda, and anti-PD-1 therapy (which targets programmed cell death protein 1). T-Vec designed to stimulate the immune system, while Merck's Keytruda functions by taking off the immune system's brakes.
Keytruda was the first PD-1-directed monotherapy to enter the market in the United States. But, like many other immunotherapies, the focus is rapidly switching from stand-alone treatments to what could be possible with duo-immunotherapies. With two mechanisms of action in synergy, duo-immunotherapies can bring much higher response rates.
In terms of T-Vec and Keytruda, Amgen and Merck have expanded their collaboration to include studies for patients with recurrent head and neck cancer.
Amgen amps it up -- out of the clinic and headed to a pharmacy near you
While Amgen's duo-immunotherapies are still in clinical trials, that's not true about T-Vec as a monotherapy. The FDA gave Amgen the thumbs-up six months ago for T-Vec's injection into tumors that cannot be surgically removed. The European Commission followed suit earlier this year, and the vaccine is now being commercialized.
As a monotherapy, T-Vec battles melanoma and relies on the effects of a genetically modified version of the cold sore (herpes simplex) virus. Like many other viral therapies, the treatment is more effective in later-stage cases of cancer, where tumor cells have dislodged from the primary tumor. In T-Vec's phase 3 trial, the highest level of durable responses were seen in patients with stage 3 melanoma, although the goal of statistically significant increased survival was not met. Still, T-Vec caused long-lasting responses, even in tumors that were not injected. In short, T-Vec has some limitations, but it also has promise.
Early days for investment -- but stay tuned
Thus far, analysts have paid scant attention to oncolytic viruses, likely because immediate investment opportunities are limited. Current research is mostly confined to academic institutions or volatile micro caps, which often lack the financing to keep pushing development through later-stage trials.
The T-Vec program was originally started by BioVex, a small company later purchased by Amgen. Even with Amgen's fairly deep pockets behind it, T-Vec faces formidable competition in melanoma, including Novartis', Mekinist and Tafinlar, as well as Merck's lambrolizumab. Still, at least one analyst has estimated peak sales of $500 million for T-Vec.
While T-Vec won't have a huge impact on Amgen's top or bottom line in the near future, it's a field that is likely to grow extremely rapidly. In fact, BCC Research, in its report "Cancer Immunology and Oncolytic Virology," claims the global market for cancer immunotherapies should reach nearly $67.9 billion by 2018. BCC expects a global five-year compound annual growth rate (CAGR) of 14.7%. The North American market's slightly higher 15% CAGR should take it to $30 billion by 2018.
Oncolytic viruses currently represent a tiny segment of the overall market, but these treatments have an important characteristic that distinguishes them from other immunotherapies: a lack of side effects. Because viruses are so highly specific, they tend to have excellent safety and tolerability profiles. T-Vec, for example, invades both cancerous and healthy cells, but is unable to replicate in healthy cells, so they are unaffected, and side effects are mild.
"Viruses are professional gene delivery vehicles," says Dr. Stephen Russell, leader of the Gene and Virus Therapy Program at the Mayo Clinic Cancer Center. "We are now able to harness that." It's something to think about the next time a nasty virus lays you low. Maybe someday you will reap a lifesaving benefit from being infected by a genetically engineered form of the common cold. Even today, virus-based treatments are offering hope to patients facing the bleakest prognosis.