One of the world’s biggest drugs might not exist if its research hadn't flopped in a major way

Photo courtesy Peter Hurley

In 1998, a drug called Remicade made history for becoming the first of its kind to get approval.

Remicade, which was designed to treat autoimmune diseases like Crohn's disease and rheumatoid arthritis, made $9.4 billion in sales in 2014.

But getting there wasn't easy.

Business Insider spoke with Dr. Jan Vilcek, the scientist credited with discovering Remicade, about how the drug went from a failed cancer treatment to a groundbreaking drug. Vilcek, a microbiology professor at New York University, wrote a memoir about his life and work called "Love and Science" that will be available in February 2016.

A promising protein

In the 1970s, scientists made a fascinating and promising discovery.

They found a protein called tumor necrosis factor, or TNF. The body makes TNF as part of an immune response to foreign organisms in the body, including bacteria and tumor cells. 

"Initially TNF was discovered during studies of the growth of tumors, specifically some transplant-able tumors in animals," Vilcek said. "It was found that TNF can block the growth of these tumors and in some cases it can even produce a complete cure from these cancers. That created a lot of excitement and interest in trying to develop TNF as a therapeutic agent for cancer."

So they moved forward, trying out the use of TNF in human trials. Soon, they got the attention of several drug companies, like Centocor (now Janssen Biotech) and Genentech that saw potential in using it as a way of supporting the body's own immune system to treat cancer. This was revolutionary: Harnessing the immune system to fight cancer was so far nothing more than a pipe dream in the oncology community.

Within a few years, however, their hopes were dashed: The protein, they discovered, was way too toxic to be used in people — even at low doses that wouldn't help fight the tumor

Photo courtesy Peter Hurley

Not a cancer cure, but something else

But not all researchers gave up. 

Some, like Vilcek and his colleagues, began studying TNF more closely. And rather than looking specifically at cancer patients, they studied how it worked in healthy people and in people with other diseases. That's when they noticed that in healthy people, TNF worked as a mediator for bacterial and viral infections. In the body, when TNF senses a foreign invader, it sends signals to the immune system to attack the invaders and keep the body healthy.

But they quickly discovered that, as the idiom goes, there could be too much of a good thing with TNF.

In people with autoimmune disorders, the TNF signaling process goes awry, and the immune system begins attacking its own healthy cells rather than those of invaders, causing painful symptoms like inflammation.

By blocking the TNF, Vilcek realized, you could suppress the symptoms of the autoimmune disorder.

"As a result of other studies, it was found that TNF plays a role in inflammation in autoimmunity," Vilcek said. "If you can block TNF, you can prevent the symptoms of autoimmunity and inflammation."

It wasn't exactly the TNF-boosting cancer treatment he'd had in mind. But it turned out that inhibiting the TNF protein was incredibly useful in treating the symptoms of people with autoimmune disorders such as rheumatoid arthritis, psoriasis, and Crohn's disease. So, Vilcek focused on finding a treatment to keep TNF at bay. 

"We developed an antagonist to TNF ... that binds TNF and thereby prevents its action in the body," he said. "That's what became Remicade."

The first drug of its kind

Remicade, which is owned by Johnson & Johnson's biotech arm Janssen, was officially approved to treat severely active Crohn's disease in 1998, becoming the first TNF inhibitor on the market. It's given through an intravenous infusion that needs to be administered by a doctor every eight weeks. Since its first FDA approval, it's gone on to be approved to treat other autoimmune disorders including ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.

That research also paved the way for other TNF inhibitors, such as blockbuster drugs Enbrel and Humira, which are also used to treat autoimmune disorders. Of the best-selling drugs in 2014, Humira came in first with $12.54 billion in sales and Enbrel rounded out the top five with $8.54 billion in sales.

According to Remicade's website, the drug has been used to treat more than 1.8 million people in the world. 

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