Crohn's disease drug effective in phase 2 trial

Reuters Health Information: Crohn's disease drug effective in phase 2 trial

Crohn's disease drug effective in phase 2 trial

Last Updated: 2015-03-18

By Gene Emery

NEW YORK (Reuters Health) - Researchers testing an experimental drug for Crohn's disease say they saw remission rates as high as 65% for people with the chronic inflammatory illness in a phase 2 study.

The drug is mongersen, previously called GED-0301. An oral drug, it is designed to be released in the terminal ileum and right colon, an area that tends to be the focal point for Crohn's inflammation.

"It's nothing like anything that's currently being used to treat Crohn's disease," Dr. Amar S. Naik, a gastroenterologist at the Loyola University Health System in Maywood, Illinois, who was not involved in the research, told Reuters Health by phone "The proposed mechanism of action is completely novel."

He said the study, which involved only two weeks of treatment, was essentially a test of induction therapy. The important question of how the drug might perform as a maintenance therapy remains to be seen.

About a third of patients do not respond to standard care with immunosuppressive drugs and anti-tumor necrosis factor alpha antibodies. The effectiveness of treatment can also diminish over time.

The double-blind, placebo-controlled, phase 2 test at 17 centers in Italy and Germany involved 166 adults with moderate-to-severe Crohn's. Three doses were tested in addition to placebo. Treatment was given daily for two weeks, and patients were evaluated at days 15, 28 and 84.

The findings appear in the March 19 issue of the New England Journal of Medicine.

The two-week time period "was selected taking into account results of the phase 1 study showing that the majority of the hospitalized patients had clinical response/remission following one-week treatment," the chief author, Dr. Giovanni Monteleone of University Tor Vergata in Rome, told Reuters Health in an email.

"The effect was rapid in onset and durable in many patients," the research team reported.

By day 15, remission rates were 65% with 160 milligrams daily, 55% with 40 milligrams, 12% with 10 milligrams and 10% in the placebo group.

By day 28, the number of patients who had seen a decline of at least 100 points on a 601-point scale measuring the severity of Crohn's symptoms was 72% in the 160 mg group, 58% in the 40 mg group and 37% in the 10 mg group -- all significantly greater than the 17% in the placebo group.

"Such an improvement indicates that patients feel clinically better even though some Crohn's disease-related symptoms/signs persist," Dr. Monteleone said.

"All three groups receiving mongersen had a significantly greater rate of clinical response than did the placebo group, which suggests that even a dose of 10 mg per day may be therapeutic in a subset of patients," the researchers wrote. "Direct head-to-head studies are required to ascertain the benefit of mongersen relative to other currently available drugs in inducing and maintaining remission in Crohn's disease."

Dr. Naik said he was struck by the response rate among placebo recipients, which was unusually low for a Crohn's study.

The overall rate of adverse events was 5%. The serious adverse events usually involved complications or symptoms of Crohn's. About 65% of the side effects were mild.

"Is it too good to be true? Should we be guarded and be cautiously optimistic? I probably fall into the cautiously optimistic pool," said Dr. Naik. One issue will be the long-term durability of the therapy, which is a problem with established treatments.

"We strongly believe that further studies are needed to optimize the dose and duration of the treatment in both induction and maintenance phase as well as to study the long-term risk/benefit profile of mongersen," Dr. Monteleone said.

Giuliani, the Italian pharmaceutical company, paid for the study under contract to the privately-held Dublin-based Nogra Pharma Limited. In April, Nogra entered into a global licensing agreement with New Jersey-based Celgene Corporation to develop and commercialize the drug. Celgene paid for editorial assistance in writing of the paper.

Where mongersen would fit in with the various therapies for Crohn's isn't known. "As of right now there are no head-to-head trials with any treatments for Crohn's disease -- nothing," said Dr. Naik.

A spokeswoman for Celgene said enrollment in a phase 3 trial is expected to begin sometime this year.

"If the phase 3 results are along the line of the phase 2 results, this is a big deal," said Dr. Naik. "It's a game changer."


N Engl J Med 2015.

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