New FDA-approved drug is offering hope in spinal muscular atrophy

Spinraza spinal muscular atrophy
Sofia, now almost 3, was not predicted to live to age 2, let alone stand or walk.

All signs were positive when Sofia Wylie was born: normal term delivery, great Apgar scores. “But at her two-month checkup with the pediatrician, she wasn’t lifting her head well, and her reflexes were weak,” says her mother Natalia. “She was like a rag doll.”

The pediatrician referred the New Hampshire family to a neurologist. Sofia received genetic testing, and the news wasn’t good: she had spinal muscular atrophy (SMA), a rare paralyzing disease. Even worse, she had the most severe form, SMA Type 1, which starts in infancy. Usually babies with this form, also known as Werdnig-Hoffmann Disease, rapidly lose muscle strength. Ninety percent die by the age of 2 years from respiratory failure unless they receive aggressive and invasive respiratory support.

“The neurologist said, ‘I’m very sorry, but this is a terminal disease. Enjoy the little time you have together,’” recalls Natalia.

Sometimes called a baby version of ALS, SMA is the number one genetic cause of infant mortality. But just before Christmas, the Food and Drug Administration (FDA) approved a new drug called Spinraza (nusinersen) that has given Sofia another chance.

Under the wire

We were so nervous because we didn’t know if Sofia would get the drug or not.” Even her doctors didn’t know. After crying for several days, Natalia and her husband Jason found themselves unwilling to accept the neurologist’s word on Sofia. They requested to be seen by the SMA team at Boston Children’s Hospital.

“I said, ‘get us there,’” says Natalia. “We got on board very quickly, because time wasn’t on our side.”

Their meeting with the SMA Clinic team, directed by Dr. Basil Darras, couldn’t have come at a better time. Boston Children’s SMA research program was about to launch a multicenter Phase 3 trial of a new drug for SMA (known then as SMNRx), led by Darras.

The clinical trial was only enrolling babies under 7 months old. But Sofia had to wait for two more months while the trial, called ENDEAR, was being finalized.

In August 2014, at 4½ months, Sofia enrolled. She became the first baby in the world to receive the drug.

“For every two kids treated, one would get the placebo,” says Natalia. “We were so nervous because we didn’t know if she would get the drug or not.” Even Darras didn’t know.

Taking steps

Spinraza spinal muscular atrophy

Since then, Sofia has been treated every four months, through an injection into the fluid around her spinal cord. By December 2014, four months into her treatment, Sofia was starting to gain better head control, a sign that she was getting the medicine, not the placebo. Her arms were moving better. Her fingers and toes were wiggling. She could flex her feet and lift her legs against gravity. By her first birthday in March, 2015, she could sit in a Bumbo seat without help and reach for toys and grab them.

“From her first birthday on, she’s been progressing in strides, with no signs of stopping or regression,” says Natalia.

Today, at almost 3, Sofia can stand in her walker and propel herself with her feet. She can walk holding onto furniture or someone’s hand, though she needs a body brace and ankle braces to support her muscles. She needs to be fed through a G-tube for now because of the risk of aspirating her food, but her swallowing tests have greatly improved since the trial began, as has her breathing.

“Most kids with SMA are ventilator-dependent or need overnight ventilation,” says Jason. “Sofia is never on a ventilator, except sometimes when she’s sick, for a couple of hours at a time.”

Ongoing care

Before treatment, Jason and Natalia had to suction down Sofia’s nose to clear secretions at least 10 to 15 times daily; now she needs nasal suctioning only occasionally, and only when she has a respiratory infection. (Her throat still requires occasional suctioning.) When she’s sick, Sofia still requires aggressive pulmonary management, such as chest physiotherapy, neubulizers and use of a cough assist machine. At night, when sick, Sofia goes on BiPap, a non-invasive form of respiratory support, but since turning 2 she hasn’t required extra oxygen.

Spinraza spinal muscular atrophy
Most children with SMA Type 1 need to breathe with a ventilator to survive. Sofia only needs occasional, brief ventilation when she has a respiratory infection.

Although Natalia, a trained registered nurse, handles most of Sofia’s home care, Dr. Robert Graham of the CAPE program helps the family manage situations when her oxygen levels dip despite suctioning and BiPap.

“A big problem in our area is finding high-quality pediatric home care,” says Natalia. “The local doctors and nurses have very little experience with SMA, and some even ask what it is when I mention it to them.”

A game changer

In August 2016, the placebo-controlled trial was terminated because overall results were so promising. An interim analysis showed that 40 percent of babies given Spinraza — versus none of the babies given placebo — had achieved improvement in motor milestones (sitting, crawling, walking). All children were then switched into an open-label study where all receive Spinraza. Sofia, having completed the blinded study, entered the open-label study in November 2015. Natalia still doesn’t yet know for certain whether she was receiving Spinraza all along, but it seems highly likely.

Spinraza spinal muscular atrophy
Sofia with her big sister Samantha

A second trial, called CHERISH, involving older children with milder Type 2 SMA, was halted on November 8, 2016, after it, too, met its efficacy target. The FDA’s approval last week covers all forms of SMA, in people of all ages.

Darras is excited about Spinraza’s approval and proud of Boston Children’s pioneering role in testing it.

“For the first time we’ll have a treatment for SMA — 125 years after it was first described in the medical literature,” he says. “Until now, SMA has been treated with just supportive measures, so this approval is a game-changer and a model for how drugs can sometimes get to the finish line fast. We also believe that Spinraza has the potential to prevent SMA if we detect it by newborn screening and treat babies before they develop any symptoms or signs of the disease.”

Sofia’s last treatment — with Spinraza — was in October 2016 and she continues to show improvement. Her image will be used in the drug company’s advertisements.

“We can do almost everything now as a family,” says Natalia. “Now that there’s a treatment for SMA, families have the opportunity to create lifelong memories with their little ones who have this disease. It may not be a cure yet, but it’s pretty close.”

Learn more about the Spinal Muscular Atrophy Program at Boston Children’s and learn more about Spinraza (nusinersen) in this Q&A with Basil Darras, MD.