Coronado Biosciences Inc of Burlington, Massachusetts, is developing what it hopes will be the first in a new class of treatments for autoimmune conditions.
The treatment is based on a pig parasite. Each dose of the drug consists of thousands of microscopic parasite eggs, culled from pig faeces, 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 haepatology at Tufts-New England Medical Center in Boston and an adviser to Coronado.
How the study will work
The company is preparing to enrol 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 product, known as trichuris suis ova (TSO), in Europe. The two companies plan to share data when filing for marketing approval in 2016 or 2017.
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".
"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.
Yet, today in many parts of the world these organisms are kept at bay with an array of antibacterial soaps, detergents and sanitising gels.
Problem with standard treatments
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 hypothesise 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, which include injectable drugs that block tumour necrosis factor, depress the immune system and increase a patient's risk for infection.
"With the pig whipworm, there is no permanent infection, no real possible side effects," said Coronado's chief executive officer, Bobby Sandage Jr.
Sandage said about a third of patients experience some gastrointestinal discomfort, such as diarrhoea 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 sceptical 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!'"
"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 II 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 US 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.
(Reuters Health, August 2012)