By Mary Welch

Repligen Inc. officials reacted strongly to a preliminary study by the National Institutes of Health (NIH) suggesting that a single dose of secretin failed to benefit children with autism, a report that also caused its stock to drop significantly.

The Needham, Mass., company's stock fell Tuesday on the NIH news, which was embargoed for distribution until after the stock market closed Wednesday. Nevertheless, Repligen's stock (NASDAQ:RGEN) closed Tuesday at $3, down $1.406, or 32 percent. The stock gained 18.75 cents Wednesday to close at $3.187.

The study, published in the Dec. 9 issue of the New England Journal of Medicine, was sponsored by the National Institute of Child Health and Human Development, an NIH affiliate.

"If you give one dose of [the cancer drug] Taxol you won't get a benefit, either," Walter Herlihy, Repligen's CEO, told BioWorld Today. "We have consistently maintained that a single dose would not produce significant results in a general group of autism spectrum patients."

The NIH study involved 56 children with autistic disorders. Of those, 28 received a single intravenous dose of synthetic human secretin, the others a saline solution. Behavioral tests were administered at intervals of one day, one week and four weeks after the treatment.

The children were evaluated by 16 different measures of behavior and, according to the study, the secretin treatment did not result in statistically significant improvements in behavior. Although improvements were seen on six of the behavioral measures, the improvements were not significant.

The study's lead investigators said the study had several limitations, including that improvement may have come after the last behavioral update of a month after treatment. In addition, they said that possibly more than one injection might be required before noticeable results could be seen.

"We have been unable to show any benefit from the secretin treatment," Adrian Sandler, of the Center for Child Development at Thoms Rehabilitation Hospital in Asheville, N.C., and one of the two lead doctors in the study, said in a statement. "This suggests that secretin should be avoided as a treatment for autism until more information is available."

James Bodfish, of the Western Carolina Center and the University of North Carolina at Chapel Hill, N.C., was the other lead doctor in the study. He told BioWorld Today a single dose was given "because we were trying to replicate the anecdotal stories from parents whose children improved after a single dose. This is a valuable first step. We originally planned to do another study after this one with multiple doses."

"We're talking about an early Phase I study done with a few patients with a single dose," Herlihy said. "I can't believe the attention this study has received and the reaction - especially a study that is lacking in several key aspects. I understand that you have to go slow and walk before you can run but to dismiss secretin as not showing any benefit because of this study is the same as giving a dose of Taxol to five patients with five different types of cancers. The authors made no attempt to select a set of potentially responsive patients. Since autism has many different causes, no single treatment is likely to work for all patients."

Bodfish said the study looked at multiple subgroups and "found no difference in regard to patients who had or did not have gastrointestinal issues or dysfunctions."

Repligen will file an investigational new drug application this month to start its own trials. "I promise you there will be more patients, more dosing and we' ll target subsets of autism," Herlihy said. "If we can find that secretin helps 20 percent of autism patients then that's a major step."

Secretin is a hormone produced by a part of the intestine called the duodenum, which acts upon the pancreas to assist in digestion.

Repligen acquired the patent to use secretion for the treatment of autism from Victoria Beck, a New Hampshire mother who discovered the potential secretin-autism connection when her autistic son was treated with the hormone for severe gastrointestinal problems, and the Autism Research Institute of San Diego. (See BioWorld Today, March 11, 1999, p. 1.)