Families Push for New Ways to Research Rare Diseases

By AMY DOCKSER MARCUS

Dominick Reuter for The Wall Street Journal

Stuart Siedman, of Wellesley, Mass., with his son, Benjamin, who has Sanfilippo syndrome, a rare and fatal metabolic disease.

Parents with children who have rare and debilitating diseases are pushing to change how researchers develop medicines to treat the conditions.
The parents want different scientists researching the diseases to share data about the patients so the children won't need to participate in so many studies. In the case of Sanfilippo syndrome, a fatal, metabolic disorder, some parents have offered to raise $550,000 to cover the cost of a medical study as long as the information is shared.
The idea of sharing medical data from patients with rare diseases is gaining backing from public-health officials at the National Institutes of Health and the Food and Drug Administration. If companies, hospitals and researchers don't have to cover the full cost of such studies, there might be more efforts to develop treatments for rare diseases, these officials say. The studies can take a toll on the families, who often must travel great distances with the ailing young patients to undergo arduous medical procedures.
Companies and academic researchers, though, are often reluctant to cede control of what they consider proprietary information.
Kathy Buckley, of Saratoga Springs, N.Y., flew last month with her 12-year-old son, Matthew Rosato, and his aide to participate in a study about Sanfilippo syndrome at the University of Minnesota. Matthew can't speak and often lashes out physically due to the progression of the disease, making travel difficult. During his visits, researchers take samples of Matthew's blood, cerebrospinal fluid, and urine, perform a battery of neurological tests and sedate him for an MRI. The family will need to make the trip three times for the study, which is sponsored by biopharmaceutical company Shire PLC. SHPG +1.10%
Now, another institution, Nationwide Children's Hospital in Columbus, Ohio, will soon launch another study of Sanfilippo syndrome as it works on a potential treatment. For Ms. Buckley and other patient families, that presents a daunting prospect: Should they put their children through the testing all over again?
Ms. Buckley says she appreciates that multiple research groups are trying to develop treatments for Sanfilippo. But, she says, "We'd like to just do one…study for each rare disease."
People with Sanfilippo syndrome, named for the pediatrician who investigated the disease in the 1960s, are missing or have insufficient amounts of one of four enzymes needed to break down sugar molecules. Children appear normal at birth, but gradually lose the ability to walk, talk and eat.
An estimated 200 children are believed to be born with the genetic disorder in the U.S. each year. Currently there aren't any treatments for the disease, which usually results in death by the age of 20.
The early-stage studies being conducted into Sanfilippo syndrome don't administer a drug or treatment. Instead, researchers use these so-called natural-history studies to gain a better understanding of how the disease progresses without treatment and to track different symptoms. If a therapy eventually is developed, and a clinical trial begins, a natural-history study can be used to help evaluate whether it is working to slow or stop the disease. Shire research is aimed at developing an enzyme-replacement therapy, while the planned research at Nationwide Children's will focus on potential gene therapy.
Natural-history studies also are used in developing treatments for common diseases, like diabetes and cancers. But because the number of people with rare diseases, like Sanfilippo, is so small, patients may be needed to participate in multiple studies. And even if a natural-history study leads to a clinical trial for a treatment, there is no guarantee the same children will be allowed to participate. Patients' families with other rare diseases also are seeking to press researchers to share data from natural-history studies.
Stuart and Jennifer Siedman, whose 16-year-old son, Benjamin, has Sanfilippo syndrome, say their foundation, Sanfilippo Research Foundation, and two other family foundations have offered to raise $550,000 to pay for the Nationwide Children's natural-history study. As part of the proposed arrangement, the families say they want Nationwide to make the study data available as early as possible to other qualified researchers. Details of the agreement are still being worked out, the Siedmans say.
In a conference call between the families and the researchers held last month, the Siedmans, of Wellesley, Mass., say they told the scientists about the fatigue, emotions, and difficulties of travel that take a toll on participants in natural-history studies. "We love the researchers but they don't know the social aspects of this," says Mr. Siedman.
Douglas M. McCarty, an investigator at Nationwide's Center for Gene Therapy, says relying on another researcher's data from a natural-history study would be problematic. In order to design and run a successful clinical trial, it is crucial for the actual investigators to collect the data themselves and not rely on information gathered by other groups. "Reading about it and actually encountering and measuring it yourself are two different things," he says. Also, while some data from studies eventually get published or shared at scientific conferences, "the raw data often aren't accessible," he says. In the case of MRI tests, for example, the conclusions from the images may be available but not the images themselves.
As part of the proposed agreement with the family foundations, Nationwide Children's researchers say they are committed to sharing data with other qualified scientists so they can use if for their own trial design. The hospital also would give each family individual test results for their child.
"What we can't say we would do would be to give raw unanalyzed data as it comes in real time," says Kevin M. Flanigan, an investigator at Nationwide's Center for Gene Therapy. He estimated the researchers would need to analyze a year's worth of data and publish it to ensure it is valid before opening up the information to others.
Ms. Siedman says such a time lag in getting the data out might result in a situation where there are still multiple natural-history studies in Sanfilippo syndrome. "This is our frustration as patients," she says.
The NIH and FDA last year held a workshop on natural-history studies for academic researchers and drug companies. The agencies cited the crucial role the studies play in drug development and urged groups to work together.
"It is much more useful and informative to do one comprehensive natural-history study rather than numerous smaller efforts, and we encourage people to either pool their efforts or, even better, collaborate on one larger project," says Sandy Walsh, an FDA spokeswoman.
Shire says it has presented some data from its Sanfilippo studies at scientific conferences and will eventually publish the information in scientific journals. If outside investigators want additional information, "we would have to discuss it internally," says Howard Mayer, head of global clinical development and regulatory affairs at Shire. So far, "we haven't had inquiries," he says.
Roy Zeighami, of McKinney, Texas, signed up his 5-year-old son, Reed, who has Sanfilippo syndrome, for Shire's natural-history study in 2011, and plans to enroll him in the Nationwide Children's study, too. "My son has been knocked out three times and had spinal taps," says Mr. Zeighami.
When he heard about the natural-history study being planned by Nationwide, Mr. Zeighami says he wondered why they had to redo data that Shire might already have. The barriers for companies to enter the rare-disease drug market are already high, he says, and families don't want to make it even more difficult by arguing over natural-history studies. Still, he says he wants to see natural-history studies drawing on shared data and supports efforts by patient groups to "make the data available to everyone."
Write to Amy Dockser Marcus at amy.marcus@wsj.com

A version of this article appeared February 19, 2013, on page D1 in the U.S. edition of The Wall Street Journal, with the headline: Families Push For New Ways To Research Rare Diseases.