From no drugs to 3: Patients with spinal muscular atrophy now face hard choices

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From no drugs to 3: Patients with spinal muscular atrophy now face hard choices

by Jonathan Gardner@ByJonGardner

Jud Broadhurst was 14 years old when he began to notice the symptoms.

Playing competitive soccer, Broadhurst would fall, seemingly “for no reason,” he said. But there was one, lurking in his genes. Broadhurst had a form of spinal muscular atrophy, a rare neuromuscular condition that was causing his muscles to weaken over time.

At the time, no medicines were available to slow the relentless march of Broadhurst’s disease. Doctors said he would be in a wheelchair by age 20, a prediction he swore to defy with a lifetime of healthy eating and exercise.

But, three decades later, the outlook for patients with SMA has changed dramatically. Broadhurst, still walking at age 46, has new options and decided earlier this year to receive his first infusion of Biogen’s Spinraza.

“I will do anything humanly possible not to end up in a wheelchair,” Broadhurst said in an interview.

Since 2016, three drugs have been approved to slow or stop the disease, from the most severe “Type 1” form that typically leads to death by age two to the more mild forms, like Broadhurst’s, that can rob people of the ability to walk or swallow.

Each drug is dramatically different. Zolgensma, a gene therapy from Novartis, is a one-time treatment meant to produce long-lasting benefits. Spinraza, an RNA-based medicine, is infused at a clinic a few times a year. And Evrysdi, from Roche, is a daily medicine taken at home. Their arrival has transformed the expectations of patients, their families and the doctors who treat the disease.

“To see kids with SMA type 1 who are walking is just mind-blowing,” said Elizabeth Kichula, a pediatric neurologist at Children’s Hospital of Philadelphia.

But the availability of three such different drugs has left Kichula, Broadhurst and others in the SMA community with difficult choices, and not enough information to make those decisions. They must consider the cost of each treatment as well as the relative convenience each offers, and do so without knowing which is the most effective. None of them have been tested against another, and the long-term benefits of each are still being studied.

“The tricky part is that there are still a lot of unknowns,” said Rebecca Scharf, a pediatric neurologist at the University of Virginia.

For the companies that make each drug, those unknowns, and how patients respond to them, will play a large role in how widely their treatments are adopted.

Choosing the right treatment

All three drugs can be used in infants younger than two years old, making each a potential option for those with Type 1, the most commonly diagnosed and deadly form of the disease. Only Spinraza and Evrysdi are approved for use by older patients, largely those with the more mild Types 2 and 3 that account for 88% of people living with the disease, according to the nonprofit SMA Foundation.

Each drug has its strengths and weaknesses, though.

As a gene therapy, Zolgensma is meant to permanently change the course of the disease with a single treatment. But because the longest patient exposure so far is only six years, patients’ families have limited information on whether it could be considered a cure, and whether any safety problems might arise much later on. Zolgensma also costs $2.1 million, the highest per-dose price of any medicine in the world.

Spinraza and Evrysdi, by comparison, are chronic therapies. Biogen’s drug is infused into the spine and costs $125,000 per use. Patients need six doses over the first year and three every year afterwards. Roche’s medicine, a once-daily oral liquid, costs a maximum of $340,000 per year, though the actual price is tied to a patient’s weight.

The choice between treatments looks different for each patient.

Jase YoderCourtesy of Cheryl Yoder 

Cheryl Yoder’s son Jase, now five years of age, was enrolled in a study of Spinraza as an infant and has been receiving infusions since he was one month old. While driving to a recent appointment, “I told the Lord I would love it if we wouldn’t have to do this all the time. If there could be a one-time thing that would be amazing,” she said.

Jase is now too old to receive Zolgensma.

The “intrathecal” injections, or spinal taps, used for Spinraza are also invasive procedures that must be done under specialized care in a healthcare facility, requiring local, or in some cases general, anesthesia. The injections can be an annoyance for some or a barrier to use for others, depending on age or overall condition.

Repeated sedation is potentially worrisome in infants and children because of possible long-term effects on developing brains. And younger children in some cases must be taken out of school before their Spinraza infusions to avoid upper respiratory infections that can make it risky to receive general anesthesia.

Older patients on Spinraza who spoke with Biopharma Dive had more modest concerns.

Broadhurst, who flies from his home in Colorado to Phoenix to receive Spinraza treatment, doesn’t view the spinal injections as overly burdensome. Twice, he’s gotten a dull, aching headache. “The infusion takes five minutes, tops,” he said. “Every now and then they’ll brush up against a nerve, and it feels like a lightning bolt.”

Janelle Fiesta, 24, was diagnosed when she was one year old, and as a result of the condition has had a spinal fusion and a metal rod placed into her back.

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