As Experimental Treatments Grow, Families Face Tough Choices

By Amy Dockser Marcus Features Dow Jones Newswires

Results from clinical trials testing two therapies to treat a rare disease called spinal muscular atrophy illustrate a growing dilemma for families as expanding knowledge of genetics leads to new potential treatments -- and tough choices.

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Families of children with rare diseases who once had no options must now decide among experimental therapies that may not offer a cure or work at all. And going down one path may preclude participation in later, more successful trials or close other options; researchers typically prefer to study untreated children to get the clearest picture of whether experimental therapies are working.

Two new studies, published in the New England Journal of Medicine, report findings from a gene-therapy trial sponsored by AveXis Inc., and a trial of a so-called antisense therapy, nusinersen, funded by Biogen and Ionis Pharmaceuticals. The trials enrolled children with spinal muscular atrophy type 1, the most severe and prevalent form of the motor neuron disease. Many children with SMA type 1 don't survive past the age of 2.

Both therapies aim to increase production of a crucial protein necessary for the nerve cells in the spinal cord and brain to work, with the aim of improving motor function and survival.

While neither therapy currently is a cure, investigators in both trials reported that children who were treated earlier did better -- adding to the pressure families feel as they try to decide what options to pursue.

In the nusinersen study of 122 infants, a significantly higher percentage of infants who received the drug showed improvement compared with infants who didn't. The Food and Drug Administration approved the drug, sold as Spinraza, in December 2016, and researchers reported the final data analysis Wednesday. Spinraza requires repeated administration via spinal tap every four months.

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In the gene-therapy trial, which enrolled 15 infants, all the children were alive as of August but the 12 children in the highest-dose group fared the best and achieved various major milestones, such as sitting up, the paper reported.

AveXis is enrolling patients in a new trial of the therapy at 16 sites in the U.S., which it hopes will lead to FDA approval. But any child who participated in the nusinersen trial or takes Spinraza isn't eligible to enroll in the new gene-therapy trial, says Sean Nolan, president and chief executive of AveXis.

Doctors say there are two other SMA type 1 experimental therapies for which trials are recruiting or expected to recruit in the U.S. in the near future, but add that children who take Spinraza likely won't be eligible to enroll in those either.

"The choices families in the SMA community are facing will apply to any number of genetic conditions," says Robert Graham, a specialist in critical-care medicine at Boston Children's Hospital who helps care for SMA patients but wasn't involved in these latest studies. "The SMA community is encountering the issues early, but the questions are not going away."

Richard Finkel, a pediatric neurologist at Nemours Children's Hospital in Orlando, Fla., is the first author of the nusinersen study and a member of the data-safety-monitoring committee in the gene-therapy trial. He says he sat down with parents of infants with SMA for decades, and "I had to send them home with basically a death sentence. Now for the first time, I have something meaningful to offer them."

But parents and doctors must weigh whether to give a child Spinraza, which is the only FDA-approved drug to treat SMA, or wait to see if the child is eligible for a future trial.

"If you start Spinraza, you close the door on the opportunity to get into a gene-therapy trial or other studies," says Dr. Finkel.

Eric and Valerie White of Cumming, Ga., say when their son Henry was diagnosed with SMA in January 2016, the prospect of gene therapy -- involving a one-time infusion that takes an hour -- was enticing, but there were no open slots or guarantee Henry would qualify for a future one. Enrolling in the nusinersen trial meant a chance that Henry would be randomly placed in a trial arm that didn't receive the drug. "It was extremely unnerving," says Mr. White.

They decided the trial was the best option. Henry, who will be 2 at the end of the month, doesn't walk and has other issues associated with the disease. But his parents say he now rolls, moves his arms and legs, "gets into trouble like any 2-year-old" and, most important of all, is still alive.

The couple continues to follow the gene-therapy trial as it moves forward, says Mr. White, even though they know they made their choice and, "right now, Henry doesn't qualify."

(END) Dow Jones Newswires

November 01, 2017 17:38 ET (21:38 GMT)