A Revolutionary Decade for Spinal Muscular Atrophy Therapies

Over the last eight years, there has been an unprecedented transformation in the spinal muscular atrophy (SMA) treatment space, with the approval of multiple new treatment options that have changed the lives of many people living with SMA.

In December 2016, Biogen’s Spinraza became the first FDA-approved treatment for SMA, followed by Novartis Gene Therapies’ Zolgensma in 2019 and Genentech’s Evrysdi in 2020.

Each therapy is unique. Zolgensma is a one-time gene replacement therapy for children ages 2 and younger delivered via intravenous (IV) infusion. Spinraza is an antisense oligonucleotide (ASO) administered every four months intrathecally (via spinal tap), and Evrysdi is a liquid medicine taken orally (by mouth) every day. Spinraza and Evrysdi are approved for all ages, from infants to adults.

Although different, these therapies have one thing in common: They’ve ushered in a new era of hope and possibility.

A changed treatment landscape

Before Spinraza’s approval in 2016, the standard of care for SMA was limited. Now, FDA-approved therapies have changed how clinicians treat the disease. In addition, the prevalence of newborn screening across the United States has played a major part in diagnosing the disease before symptoms manifest.

“We’re able to treat newly diagnosed infants much earlier, and it really is quite remarkable how these treatments are changing the natural history of the disease,” says Charlotte Sumner, MD, MDA Care Center co-director and Professor of Neurology, Neuroscience, and Genetic Medicine at Johns Hopkins University School of Medicine.

The availability of new therapies has also had a significant impact on adults living with SMA. “Many patients feel that they’ve stabilized and their symptoms are no longer progressing,” Dr. Sumner says. “Their outlook is transformed; what they were facing previously was this slow but relentlessly progressive disease process.”

A more positive outlook can have real-life ramifications. “One of my adult patients decided to pursue driving, which she had never done before because she never had the confidence that she would have the ability to do that in the long term,” Dr. Sumner says.

While the new SMA therapies have generated hope, it’s important to keep in mind that not everyone with SMA experiences the same benefits from a particular therapy — results vary from patient to patient. “Variability may stem from patient factors, such as baseline disease severity and age of treatment initiation, to drug factors, such as optimal drug delivery,” Dr. Sumner says.

Some people find more success using one therapy over another or using more than one. Many community members are happy to share their experiences to help others understand how these therapies could fit into their lives or benefit them.

Community members share SMA therapy experiences

Sory: Feeling stronger

In 2016, Sory Rivera of Tyler, Texas, who lives with SMA type 3, noticed a sudden progression in her condition.

“I started declining really fast, losing abilities,” Sory says. “Doing all the things that I used to do was getting really difficult — eating on my own, doing my makeup, handwriting, driving.”

In March 2018, at age 30, Sory received her first Spinraza treatment. The results were immediate.

“I noticed a significant increase in my abilities and stamina,” she says. “I wasn’t tired all the time. I had a boost of energy that I hadn’t had in a long time.”

Today, Sory, 36, is a writer and public speaker and has regained a lot of the strength she had before starting the treatment. “I can drive again. I can write for about an hour without getting tired. I’m back to doing all the things I used to do before I started Spinraza,” she says.

Although Sory is eligible to take Evrysdi, she’s comfortable staying on her current treatment regimen. “I’ve been on Spinraza for six years now,” she says. “I know the side effects and how it feels. It’s minimal discomfort. As we say in Texas, ‘If it ain’t broke, don’t fix it.’”

Overall, her experience with Spinraza has been positive. “When the decline in my abilities happened, it was heartbreaking,” Sory says. “After Spinraza, I’ve gained a sense of peace and joy that I can continue living my life like I used to.”

Dana: Regaining independence

Dana Carpenter of Austin, Texas, who lives with SMA type 2, was excited to begin taking Evrysdi in October 2020 after she noticed her strength declining.

“It was getting pretty scary. My SMA is pretty advanced, and I only have use of my thumbs and neck,” Dana says. “My swallowing was getting very weak, I was fatigued all the time, and I had lost the ability to drive my chair.”

Dana, 47, who works part-time as an accessibility tester for websites and apps, was drawn to Evrysdi’s convenience.

“I was really excited when Spinraza was first approved, but I knew I wouldn’t be able to keep up with the treatment,” she says. “So when Evrysdi was approved, I decided to jump on it. Taking this treatment orally and at home made my decision easier.”

Since starting the treatment, her stamina has increased, her swallowing feels stronger, and she has been able to drive her power wheelchair again.

“Having that independence back has been life-changing,” she says. “I feel as if my outlook on life has got brighter. I have peace of mind that I am doing something to slow the progression of my disease and taking control of my life in a way that was not afforded to me in the past.”

Kenzie: Life-changing impact

Kenzie Graves was born in 2019 with SMA type 1, the most severe form of the disease. Fortunately for Kenzie, Zolgensma was approved a few weeks before she was born. And Missouri, where Kenzie lives with her parents, Sydney and Kody, has routine newborn screening for SMA.

“The timing was surreal for us,” Sydney says. “We were very lucky.”

After Kenzie was diagnosed at 1 week old, her parents consulted with Kenzie’s neurologist and decided she’d take Zolgensma at 1 month old.

Then, in 2020, just after Kenzie’s first birthday, Evrysdi was approved.

“Around that time, she was standing but not really crawling,” Sydney says. “We decided to go ahead and try Evrysdi, and she started crawling a couple of months later. She started walking on her own at about 21 months.”

Kenzie’s development has continued ever since. “Today, she’s doing very well overall. She continues to meet most developmental milestones,” Sydney says. “The only things she can’t do are jump and run. And she does wear out more quickly and needs more sleep.”

Overall, the impact of these therapies has been life-changing for Kenzie, who will start kindergarten in the fall, where she is sure to make friends. “She’s very happy, bubbly, outgoing, and loves people,” Sydney says. Adds Kody: “I like to say she has unwavering exuberance.”

Treatments on the horizon

Although the SMA treatment landscape has already been transformed, there is more work to be done.

Dr. Sumner notes that the three therapies approved for SMA are not just new drugs but new types of drugs for neuromuscular diseases. Researchers are still learning how these therapies work and the most effective ways to administer them. In addition, the research community continues to search for newer and more effective therapies.

Dr. Sumner identified three approaches that SMA researchers are investigating now:

1. Improving the existing approved drugs and how they’re administered

“With nusinersen (Spinraza), for example, one idea is to give a higher dose,” Dr. Sumner says. “A higher dose may provide better delivery to all the motor neurons that need it.” Clinical trials are ongoing to see if higher doses are well-tolerated and potentially more effective.

Researchers are also trying to improve the chemistry of existing drugs. “There’s a new type of ASO that could potentially replace nusinersen,” Dr. Sumner says. “It would allow much less frequent dosing — perhaps once every nine months, or maybe even once a year. This drug is in an early phase clinical trial.”

2. Trying combinations of approved drugs

Each SMA therapy was developed and approved on its own. Researchers want to know if there are optimal ways to combine them for greater benefits.

“There are ongoing trials with sequential therapies to see if, having received one drug, one could later add another drug to improve efficacy,” Dr. Sumner says. She points to a series of trials testing that idea.

3. Add a second drug that targets a distinct pathway contributing to disease to further optimize the effect of an approved therapy

The approved therapies for SMA all seek to treat the disease by helping the body produce more survival motor neuron (SMN) protein, which motor neuron cells need to survive. However, there may be other ways to prevent or restore muscle function.

“The idea that’s furthest along is to support muscle by mechanisms independent of SMN protein induction,” Dr Sumner says.

For example, we know that when motor neurons are sick, muscle fibers become smaller and weaker. Developing a drug targeting myostatin, a molecule that inhibits the growth of muscle fibers, could promote muscle growth. Several trials are studying combining a myostatin inhibitor with one of the three approved therapies to see if that would be more effective than one of the current drugs alone.

Looking to the future

Although there’s a lot of work still to be done, Dr. Sumner believes the future is bright. “It’s remarkable what we’re seeing across the SMA space,” she says.