http://www.nytimes.com/2013/06/07/business/an-experimental-drugs-bitter-end.html?pagewanted=all&_r=2&
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| Holly Usrey-Roos, right, with Parker, 14, and Allison, 10. Both have fragile X syndrome. Ms. Usrey-Roos said Parker was helped by the drug arbaclofen. |
By ANDREW POLLACK
Published: June 6, 2013
Holly Usrey-Roos will never forget when her son, Parker, then 10, accidentally broke a drinking glass and said, “I’m sorry, Mom. I love you.”
Daniel Acker for The New York Times
Ms. Usrey-Roos with her son, Parker. The experimental drug he took for years, she said, “opened the lid and let Parker out.”
It was the first time she had ever heard her son say he loved her — or say much of anything for that matter. Parker, now 14, has fragile X syndrome, which causes intellectual disability and autistic behavior.
Ms. Usrey-Roos is certain that Parker’s new verbal ability resulted from an experimental drug he was taking in a clinical trial, and has continued to take for three years since then. She said she no longer had to wear sweaters to cover up the bruises on her arms she used to get from Parker hitting or biting her.
Now, however, the drug is being taken away. It has not met the goals set for it in clinical trials testing it as a treatment for either autism or fragile X syndrome. And Seaside Therapeutics, the company developing it, is running out of money and says it can no longer afford to supply the drug to former participants in its trials.
The setback is a blow in the effort to treat autism since the drug, arbaclofen, was one of the furthest along in clinical trials. And the company’s decision has caused both heartbreak and outrage among some parents.
“I waited 10 and a half years for him to tell me he loved me,” said Ms. Usrey-Roos, who lives in Canton, Ill. “With fragile X, you’re like living in a box and someone is holding the lid down. The medication opened the lid and let Parker out.”
“I don’t want to go back to the way life was,” she added.
The situation raises questions about what, if anything, drug companies owe to patients participating in their clinical trials. It also points out the difficulties in developing drugs to treat autism and fragile X syndrome. If the drug worked so well in some patients, why has it not succeeded so far in clinical trials?
One reason is that the symptoms and behaviors associated with autism and fragile X vary widely among individuals, making it hard to capture the effects of a drug by looking at any one measure, like irritability or social withdrawal. Seaside and doctors who participated in the trials said that there were improvements in some aspects of behavior in some studies, just not those considered critical to a trial’s overall success.
But could it also be that the parents are deluding themselves into seeing changes that are not there? Could improvements be the result of the children simply growing older?
“It’s kind of hard to make the argument that the company should keep providing it if it’s not working,” said Dr. Michael R. Tranfaglia, medical director of the Fraxa Research Foundation, of Newburyport, Mass., which provides money for research on fragile X syndrome.
Dr. Tranfaglia, whose son has fragile X but was not in a Seaside trial, said arbaclofen appeared to significantly help about a third of patients. It also made some patients worse. Without being able to tell in advance which patients would benefit, it would be hard for the drug to succeed in a clinical trial and win approval, he said.
Similar situations have risen occasionally in the past. In 2004, patients with Parkinson’s disease protested when Amgen stopped providing an experimental drug that some patients said had restored their lives. Amgen said the drug had failed in a clinical trial and might even be dangerous.
Two patients even sued, but a court ruled the company had no obligation to continue to supply the drug to participants in its trials.
In the case of arbaclofen, parents are appealing to Congress and have started an online petition hoping to find financing for the drug’s development. They are also organizing through social media.
Seaside executives declined to be interviewed.
Until recently, Seaside, one of the few companies pursuing autism drugs, was considered a shining light by family members of those with the condition.
The company, in Cambridge, Mass., grew out of the research of Mark F. Bear, a neuroscience professor at the M.I.T. Its co-founder and chief executive, Dr. Randall L. Carpenter, has a sister with an intellectual disability.
As of a year ago, privately held Seaside had raised about $90 million. Most of it had come from the Barony Trust, run by the family of Peter Whipp, a wealthy Briton. But it apparently never was the plan for Mr. Whipp to carry the company indefinitely.
Last year, Seaside entered a partnership with Roche, the Swiss pharmaceutical giant, which provided an undisclosed amount of money in exchange for intellectual property rights covering a different class of autism drug and an option to license arbaclofen.
But given the failures in the clinical trials, Roche says it has decided not to license arbaclofen, apparently ending financial support for studies of the drug.
“We concluded that arbaclofen wasn’t going to provide that real difference for patients,” Luca Santarelli, head of neuroscience research at Roche, said in an interview.
Dr. Bear of M.I.T. said he was hopeful new financing could be found. He said the company was started to help families, “not a play to make money.”
He added, “I think the signs are sufficiently encouraging. It would be really tragic if we abandon this now.”
On May 1, Seaside announced that arbaclofen, which is also known as STX209, had not met the main goal of reducing social withdrawal in a 150-patient midstage study of children and young adults with autism. But the drug did succeed on a different measure — the clinicians’ assessment of the patients.
The drug had previously failed in a Phase 2 trial for fragile X, which is caused by a mutation in a gene on the X chromosome and affects about 100,000 Americans.
In that trial, the main goal was to reduce irritability. While it did not do that, it appeared to ease social withdrawal. So Seaside began two Phase 3 trials for fragile X, one for young children and one for adolescents and adults. This time, social withdrawal was the main measure.
But the company said recently in a letter to parents that the trial in adolescents and adults had not succeeded. Results from the trial of children should be known this summer.
In the middle of May, Seaside told doctors and patients that because of “resource limitations” it could no longer supply the drug. “We know that this termination will be disruptive and disappointing for many families,” executives said in a letter to parents.
That is putting it mildly. Christina Murphy of Holton, Kan., wrote on the Web site stx209stories set up by families wanting the drug back, that her 11-year-old son Rhett, who has fragile X, made friends for the first time ever once he started taking the drug and sang in the school talent show, overcoming his usual fear of crowds and getting a standing ovation.
“I had never in my life witnessed something like that,” she wrote. “There was hardly a dry eye among the adults in the room. I have never seen him so happy in his entire life as when he finished that song and looked out at the crowd.”
Only a few hours later, she learned that the drug would be taken away. “I am sad, I am hurt and my heart is breaking,” she wrote.
Parents and patient advocates say there could be 300 patients or more taking the drugs. Some say they were promised the drug would be available until it reached the market or was totally abandoned as ineffective.
“When I found out, I went upstairs to my husband. I was crying so hard he thought someone had died,” said Cortney AbouElSeoud of Holt, Mich.
Ms. AbouElSeoud said her 5-year-old son Ayden, who has fragile X, spoke only a few words before entering the trial last October. Now he is up to 50 words. “He talks to us and answers us,” she said. “It’s crazy and awesome to see him emerging into a little person.”
Some parents say that they feel betrayed by Seaside and that the company has not communicated enough.
“I believe I, along with many others, are entitled to a better explanation of why our lives are being turned upside down,” Lori Armer of Newport News, Va., wrote on a Facebook page for families weaning their children off arbaclofen. She and other parents wrote on the site that behavioral problems were returning as the drug dosage was reduced.
There are some options. Arbaclofen is a derivative of baclofen, a generic muscle relaxer that is already on the market as a treatment for spasticity. While there is some evidence that arbaclofen is more potent, some parents are turning to baclofen.
Others hope to enroll their children into trials of other drugs for fragile X and autism being run by Roche and Novartis.
Ms. Usrey-Roos, who works for the National Fragile X Foundation, based in Walnut Creek, Calif., said she was hopeful that if one drug worked, another might, too.
While sad that the study ended, she said, “I’m still thankful for this experience. It has given me such hope.”
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