The results of RedHill Biopharma Ltd.'s (Nasdaq: RDHL); TASE: RDHL) Phase III trial of its drug for treatment of Crohn's Disease have aroused great interest among investors, doctors, patients, and the medical community in general. Especially interested in the results were the people being tested in the trial, who rushed to find out whether acting as test subjects had helped humanity and their fellow Crohn's Disease patients, or whether it was all in vain.

The trial, the results of which were published last week, met its main endpoints (an absence of attacks after 26 weeks) and most of the secondary endpoints (the proportion of subjects without no attacks after 16 weeks). RedHill's share price has nevertheless plunged 27% since the results were published for several reasons: the company has an open shelf prospectus and the market believes that it will raise capital soon; the share price was affected by gamblers who bought before the results were published in order to sell afterwards, regardless of whether the results were good or bad; and the trial failed to achieve one of the secondary endpoints - the number of subjects still suffering from an attack after a year.

RedHill said that this figure was not significant for an assessment of the drug's long-term performance, because the long-term measure of importance to medical science is the number of patients who reached a state of no attacks in the 16th week and remained in that state until the 52nd week. There was a significant difference on this measure between the trial group and the control group. The company's clarification did not affect its share price. RedHill's market cap is NIS 557 million. The market is now waiting for the company's second quarter financials.

"Disillusionment comes only at the end of the trial"

A talk with one of the trial subjects exposes a little of what goes on behind the scenes of the clinical trial industry. We are not telling you what he said in order to express any opinion about this specific trial and its results; we want you to understand how people really arrive at the numbers that are afterwards translated into success or failure. The interviewed patient is obviously just one case.

"I have been suffering from Crohn's Disease for many years already," he says. "I take both drugs to repress the immune system and a biological drug, but I don't really feel any improvement in my situation. When I heard about RedHill's trial, I was very optimistic and hurried to sign up."

The test subject quickly concluded that he was part of the treatment group, not the control group. "I turned orange," he says. "People looked at me strangely and said, 'You got a tan, right?' My teeth became orange. I needed treatment by a dental hygienist, which was paid for by the company that conducted the trial (the contract research organization - G.W.)." The payment was part of a clause in the trial agreement that stated that the company would pay any medical expense required by a patient as a result of participation in the trial.

The patient says that his urine also became orange. "So that the test subjects wouldn't know immediately that they had received the drug and not a placebo and the principle of a double-blind test would be preserved (in which neither the subject nor the doctor knows which test subjects are from the treatment group and which are from the control group, G.W.), the company also put material that colors urine orange into the placebo," the patient explained. This protocol, of course, was coordinated in advance with the US Food and Drug Administration (FDA), which approved it.

"Globes": How long did you stay orange?

Patient: "As long as I took the drug, all of my body fluids remained orange. When we stop taking the drug, it passed after a few months, or maybe a year."

After 26 months, the patient filled out a form on which the trial results were based. "I felt well after the treatment, so I gave positive answers on the form, but there was no change in my clinical data - blood tests and such," the patient said.

The test subject says that he got a very strong feeling from the research coordinator about what he should write in the questionnaire. This bias of trial subjects towards saying what the party conducting the trial wants to hear, whether or not it is a conscious bias, a recognized phenomenon in clinical trials, is exactly what double-blind trials are designed to avoid, because the same pressure is applied to both groups. This method, however, depends on it being impossible to distinguish between the trial group and the control group.

You stopped taking the drug even though you had good results on paper in the 26th week.

"It's true that my results in the 26th week were such that I could be counted as a patient whose treatment was successful. I felt later that the treatment didn't help me and stopped it, and in the 52nd week, I was counted as an unsuccessful case. I think that my belief in the drug made me feel better. Disillusionment came only at the end of the trial when I saw that there was no change in any objective measure.

"Today, I don't regard this treatment as effective for me, but there are patients in forums of Crohn's Disease patients who say it did work for them."

Published by Globes [online], Israel business news - www.globes-online.com - on August 7, 2018

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