Learning that spinal muscle atrophy was the reason her 15-month-old son couldn’t do what others his age could was a “gut-wrenching” moment, Kristen Farrell recalled in a recent webcast hosted by Biogen. But, as Braeden turned 2, a clinical trial opened for a potential SMA treatment — known then only as nusinersen — for children his age through 14 years.
Nusinersen would go on to become Spinraza, by Biogen, the first treatment approved to treat SMA — across all disease types — by the U.S. Food and Drug Administration (FDA). Half a year later, in June 2017, the European Union reached a similar decision.
After “a lot of regression” throughout his second year of life, Braeden began showing evident signs of improvement. “We started seeing really important changes in his abilities, in his muscle tone, in his strength and his stamina” as the treatment took hold, Kristen said in a segment of Making Strides: The Science and Stories of Treating SMA, an April 29 webcast in which families with this neurodegenerative muscular disease shared their stories.
A second child, Kernan, was born about a year after her brother, and also would be diagnosed with SMA, but a somewhat milder form — type 3.
Too young to be eligible for her brother’s clinical trial, Kernan and her parents, Kristen and Jim, played a “waiting game.”
“She would fall a lot at school,” her mother said. “They would call me and say ‘she fell again,’ or ‘she stopped being able to step down onto curbs.'”
Part of the Farrell’s frustration: “We knew that there was this wonderful drug that was available in the clinical trial for kids who met the criteria — she didn’t.”
That would change a few years later, with FDA approval of Spinraza in the days before Christmas 2016, and her parents were able to quickly get Kernan the treatment.
Today, the 6-year-old has “pretty much regained” motor skills, her mother said, being able to walk with rare falls and giving little thought to curbs. She takes delight in dance lessons, saying “I do ballet and Braeden does karate.” But Braeden, who has type 2 SMA, mostly uses a motorized wheelchair to move around and practices his sport in leg braces, according to a press release from Boston Children’s Hospital, where the siblings are treated.
“We’re really so grateful that no other family will have to hear those words that we heard: That your child has SMA and there’s nothing we can do, there’s no treatment,” Kristen Farrell said.
Spinraza, an antisense oligonucleotide, works by correcting the RNA splicing of the gene SMN2. As such, it was the first SMA therapy that “highlights the power of unlocking genetic technologies and genetic medicines” to treat serious and chronic diseases, said Michael Ehlers, MD, PhD, an executive vice president and head of research and development at Biogen.
This splicing allows the SMN2 gene to produce enough SMN protein to compensate for the lack of a functional SMN1 gene, which causes SMA, said Al Sandrock, MD, PhD, the company’s chief medical officer.
The treatment would go through a number of advanced, Phase 3 trials — ENDEAR (NCT02193074) in infants, CHERISH (NCT02292537) in children ages 2 to 12, and NURTURE (NCT02386553), still ongoing, in pre-symptomatic newborns — leading to its broad FDA approval.
“We’re very proud of the fact that this drug has efficacy, not just in infants and children … but also in adults,” Sandrock said.
“Only two years ago, there was no treatment for this debilitating and sometimes fatal disease,” added James Glassman of the George W. Bush Institute, who moderated the webinar. “Today, people from many countries are receiving Spinraza, which has given hope to the SMA community.”
Spinraza is given intrathecally, meaning by injection into the spinal cord.
Kernan Farrell thought her treatments rather unremarkable. She goes to her doctor, and gets to pick which flavored anesthesia will be used — “I like to choose bubblegum,” she said, giggling — then wakes up and all is done. Afterward, “you sometimes get to have Popsicles,” she added, remembering that one special treatment earned “like five or six Popsicles.”
An adult perspective
For a 42-year-old man living with SMA type 3, who identified himself as Mike N, life was a little more challenging. Mike was given a vague diagnosis of having some type of “muscular dystrophy” when he was 4 years old. It wasn’t until eight years later, when he was 12, that doctors understood he had spinal muscular atrophy. No treatments were available to stop its progression.
“I was an angry kid,” Mike acknowledged at the webinar. “I kind of kept to myself.”
But that anger eased as he entered adulthood. “I changed that perspective on myself” in college, Mike said, describing a conscious effort to see himself as more than his disease. “There is nothing ‘wrong.’ We are normal people.”
Still, SMA often left him too tired to socialize, and the disease proved a persistent obstacle in finding suitable employment. Without work and on disability — the mortgage company he was with closed in the 2008 financial debacle, he said — he now serves on the board of his local YMCA.
Mike started on Spinraza in 2017, shortly after its approval. He described “choking up” upon hearing a treatment that might address the disease at its core existed and was being made available to SMA patients. “That was an exciting day,” he said of Dec. 23, 2016.
A sense of improvement came with the first dosing. “I felt something right away; I felt rejuvenated.”
A headache followed his second treatment, an effect common to spinal injections, but Mike thought the side effects few and benefits many: “I can bend over and get myself up to a seated position again,” he said. “I’m able to go out and spend more time with my friends and my girlfriend.”
More such treatments might be on the way, Biogen executives said as the webinar concluded.
Ehlers spoke of a type of antisense therapy, called BIIB067 (formerly, IONIS-SOD1Rx) that Biogen is developing with Ionis Pharmaceuticals, much as it did Spinraza, to treat amyotrophic lateral sclerosis (ALS) caused by mutations in the SOD1 gene. The therapy is now in a Phase 3 clinic al trial (NCT02623699) in adults; it is estimated to conclude in 2020.
“We see this as being the beginning of a coming revolution of severe neurological diseases,” Ehlers said, noting that for many of rare diseases, the underlying genetic cause is already known. As such, they can be targeted by advancing genetic therapies.