If you had a chronic and potentially debilitating condition such as rheumatoid arthritis or Crohn's disease, and swallowing the eggs of a pig parasite could help, would you do it?
The team at Coronado Biosciences Inc is betting you would.
The Burlington, Mass., company is developing what it hopes will be the first in a new class of treatments for autoimmune conditions. Each dose of the drug consists of thousands of microscopic parasite eggs, culled from pig feces, suspended in a tablespoon of saline solution to be swallowed.
In a pig, the eggs would grow into mature whipworms and reproduce, without harming their host. In humans, the same eggs barely survive two weeks. Yet in that short period they appear to modulate a patient's immune system and prevent it from attacking the body's own tissues and organs.
"It has the potential not only to be a drug but to provide insight into the cause of these diseases," said Dr. Joel Weinstock, chief of gastroenterology and hepatology at Tufts-New England Medical Center in Boston and an adviser to Coronado.
The company is preparing to enroll 220 patients with Crohn's disease in a midstage clinical trial. Participants will receive either a dose with 7,500 eggs from a pig whipworm or a placebo once every two weeks for 12 weeks.
Coronado's partner, German drugmaker Dr. Falk Pharma GmbH, is conducting a midstage trial of the drug, known as trichuris suis ova (TSO), in Europe. The two companies plan to share data when filing for marketing approval in 2016 or 2017.
Tiny Coronado, with a market value of nearly $139 million, went public on the Nasdaq stock exchange last December. If the company, which also has an early-stage cancer drug in development, succeeds with TSO, it will compete against multibillion-dollar drugs from Amgen Inc and Abbott Laboratories.
Sales of autoimmune disease drugs are expected to grow in the mid-single-digit percentages through 2016, from $34 billion in 2010, according to market research firm BCC Research.
As many as 700,000 Americans suffer from Crohn's disease, a bowel disorder. An estimated 50 million Americans have rheumatoid arthritis and as many as 7.5 million suffer from psoriasis.
The technology behind Coronado's product was developed by Weinstock and researchers at the University of Iowa, where Weinstock was affiliated before Tufts. It is based on the "hygiene hypothesis," which holds that many developed countries have, in some ways, become too clean for their own good.
Millions of organisms, including viruses, bacteria and worms, enter the body through contact with dirt. Researchers believe many of these organisms are needed to train the body's immune system to recognize and fight disease.
"Microbes have adapted to us, and us to them, and we use them to stimulate our immune system," said Dennis Kasper, a professor of medicine, microbiology and immunobiology at Harvard Medical School, who is not involved with Coronado's product.
Today in many parts of the world these organisms are kept at bay with an array of antibacterial soaps, detergents and sanitizing gels.
Studies have shown that the incidence of autoimmune disease tends to be highest in the developed world, and is highest there among upper-income groups. Weinstock and others hypothesize that the elimination of certain intestinal parasites may have led to the loss in some individuals of a key mechanism for modulating the immune system.
Standard treatments for autoimmune disorders include injectable drugs that block a protein known as tumor necrosis factor. They include Amgen's Enbrel and Abbott's Humira. These depress the immune system and send its army of infection-fighting cells back to their barracks.
They also raise the risk of serious infection, including tuberculosis, and some types of cancer. Coronado's chief executive officer, Bobby Sandage Jr., says that is one reason why patients with serious conditions would choose the company's drug despite its provenance.
"With the pig whipworm, there is no permanent infection, no real possible side effects," he said.
Sandage said about a third of patients experience some gastrointestinal discomfort, such as diarrhea or cramping, after the first or second dose, though the symptoms typically go away after a day or two. He said patients need to stay on the drug indefinitely to keep symptoms at bay.
"It really does take a bit of getting used to. But once you talk to patients and they understand the theory, they accept it. We have had no trouble recruiting," said Dr. John Fleming, a professor of neurology at the University of Wisconsin who is testing the drug in patients with multiple sclerosis.
Others are skeptical about the drug's chances of gaining broad acceptance.
"This is not like taking a pill or even an injectable," said Steve Brozak, an analyst at WBB Securities who follows the biotechnology sector. "Here you are taking parasites that live in a pig's intestine, putting them into little vials and saying, 'Bottoms up!'"
Humans and their parasites have evolved in tandem for millennia. Most parasites have found ways to feed off humans without killing them, and some have become important for health.
A parasite that lives comfortably in humans may not be able to survive in another species, and vice versa. For the purpose of creating a drug, that is a good thing.
"What we know from the pig whipworm is that when you give it to people, it is destroyed in the gut," said Fleming. "It doesn't come out, so you have to keep giving it."
Initial results from early trials of the drug in patients with multiple sclerosis are promising, he said, though much more study will be needed to prove efficacy.
"I'm pretty convinced about the safety," he said.
Coronado has rights to the drug for all autoimmune conditions in North America, South America and Japan. Dr. Falk holds the rights to market the drug for gastrointestinal disorders in Europe.
By next summer, 250 people in the Phase 2 Falk study will have taken the drug for three months, and data is expected to be released around the same time. Results from Coronado's study should be released in the second half of next year.
Approval from regulators could involve an unusual set of hurdles, as there is little precedent for such a product. Sandage said conversations with the U.S. Food and Drug Administration and European regulators are going well.
"They are very well aware of what the product is, and we have been through a lot of stuff with them and they seem very happy so far," he said.
New systems have had to be introduced to clean the eggs. Traditional biologic drugs are purified using high heat or radiation, but Coronado can't do that: It needs the eggs to stay alive. So the company uses an acid wash, which the eggs can withstand because they have evolved to pass through the stomach acid of their host.
"A lot of time was spent figuring out purification techniques," Sandage said.