[Editor’s Note: This is part of a series of articles into the discovery and development of Evrysdi, SMA’s newly approved disease-modifying therapy and its first oral and at-home one, as well as the scope of SMA issues and treatments. Here, we talk with an Indiana man who began treating his type 3 disease with Spinraza before switching.]
Jim Willison isn’t one to wait around. In the 20 years before he finally could start treating his spinal muscular atrophy (SMA) type 3, he had sought out and took part in nearly every SMA clinical trial reasonably close to his Indiana home.
Willison, 61, began using Spinraza (nusinersen, by Biogen), the first approved disease-modifying therapy for infants and adults with SMA, in February 2018, and thought it helpful: the treatment provided “a bit of strength,” most notably aiding with endurance.
“I especially noticed it when working out, doing repetitions,” Willison, a former volunteer fire department first responder who lives in Lafayette, said in a phone interview with SMA News Today. “It also manifested itself in being able to transfer from my wheelchair to my car driver seat.”
Spinraza works by raising levels of a functional survival motor neuron (SMN) protein that, due to mutations in the SMN1 gene, are largely absent or insufficient in those with SMA. This protein is essential for the health of motor neurons — nerve cells that control muscle movement. Updated findings from the ongoing, long-term Phase 3 SHINE extension study (NCT02594124) showed that Spinraza remained effective over years of use.
But he said he also found the gains realized with Spinraza — given via injection directly into the spinal canal — diminished between treatments.
“I would experience a noticeable decline in endurance the last few weeks between injections,” Willison said. “My injections were every four months, but the benefits lasted three.”
It had taken 10 months to get his insurance provider to approve Spinraza’s use, and a couple more months to be placed for treatment at Ohio State University, where his five doses were administered over about six months. Willison has no spinal deformities, and he had no surgeries that would’ve made the injections difficult or uncomfortable.
“The injections took about 20 minutes, and I had no problems whatsoever,” he said. “I would just sit up unsupported and bend over slightly.”
Then he read of a promising and easier-to-take therapy, called risdiplam, being tested in a clinical trial. Having participated in about five studies already — none of which helped — he was ready for another.
“I felt I was a good candidate, so I started a campaign to join it,” said Willison, who has an electrical engineering degree from DeVry University. “I said I eat right, I sleep right, I’m fit, and that I will start this trial and I will finish it. I bugged them.
“I let them know I was here and wanted to be a part of it. And that’s what it takes.”
The trial, JEWELFISH (NCT03032172), is an open-label study evaluating risdiplam’s safety and tolerability in a range of SMA patients, ages 6 months to 60 years, including those previously treated with Spinraza or Zolgensma, an approved SMA gene therapy initially developed by AveXis, now part of Novartis.
With no test site in Indiana, he was registered for the study at New York-Presbyterian/Columbia University Medical Center, where he goes every three months for examinations and to collect two months’ worth of the treatment. Because risdiplam has a shelf life of about 60 days, he said, a one-month supply is later sent directly to his home.
Willison had to stop Spinraza for at least 90 days before starting JEWELFISH, and his final injection was in August 2018. Between then and February 2019, when he entered the study, he took no medication for his disease.
Risdiplam, approved on Aug. 7 under the brand name Evrysdi, is similar to Spinraza in that it too works by increasing the ability of the SMN2 gene to produce functional SMN protein. It was developed by Roche and Genentech (a member of the Roche group), in collaboration with PTC Therapeutics and the SMA Foundation.
But Evrysdi is an orally administered liquid. As such, it is the first at-home treatment for SMA, a disease characterized by progressive muscle weakness and wasting.
Willison’s SMA journey — an accurate diagnosis took decades — began when he was 14 or 15. He noticed that friends in high school were beginning to develop physically and add muscle mass, while he wasn’t. A baseball and basketball player as a child, he tried weightlifting. It didn’t help.
“By the time I was 18 it was pronounced, and time we did something. That’s when we made our first contact with neurologists,” said Willison, who is married and has two adult daughters. “There was no clear diagnosis. ‘We don’t know what it is, have a nice life,’ is what we were told.”
Fast forward to 1998 and the rise of genetic testing, which Willison also read about. By this time, he couldn’t walk long distances with his family, and had a noticeably odd gait. But as his disease progressed year by year, he continued to maintain a health club membership.
“I always worked out to fight it as much as possible,” said Willison, who acknowledges being “the best type 3 I’ve ever met.” Partly, he credits this to a “luck of the draw,” and partly to his “very, very active” lifestyle.
Diagnosed through a genetic test — Willison is listed as type 3, with one SMN1 gene copy (harboring a mutation) and two SMN2 copies — he adapted as best he could without a disease-modifying treatment, and flourished in work in sales and engineering.
He’s also a certified emergency medical technician, and served for 22 years with the nearby Sheffield Township Volunteer Fire Department — a remarkable achievement for someone with a neurodegenerative disease — until progression forced him to leave about five years ago.
“I would do everything but lift,” he said. “As long as properly instructed people were around me, I was OK.”
Constant use of a wheelchair became necessary about four years ago, around 2016, and travel is now difficult. For the last three years, Willison has earned a living doing voiceover work in a studio he set up at his home.
Each morning as part of JEWELFISH, he said he takes 6.5 milliliters of his green, flavored liquid treatment. His assigned flavor “tries to be” strawberry.
“It’s very tolerable,” he added with a chuckle.
Evrysdi, he said, offers many of same benefits as Spinraza, but without lapses in effectiveness between doses. He credits the treatment with halting his disease’s progression.
“Everyday is good,” Willison said. “I can raise my arms multiple times while eating, and don’t tire. I can feed myself and don’t tire. When typing on the keyboard, my hands don’t get as tired. The same with brushing my teeth.”
When he resumed workouts at his gym, recently closed for 90 days to prevent the spread of COVID-19 infections, he did surprisingly well.
“I expected to do poorly and be very sore, but risdiplam has allowed me to maintain my level of strength,” Willison said. “I don’t think I would’ve worked out nearly as well had I not been taking it every day.”
He said that he’s had no noticeable side effects from the medication.
Besides travel to New York for JEWELFISH, Willison uses an app on a smartphone given to study participants for five daily tests: one to see how hard he can push, another to gauge lung capacity, and others for dexterity, balance, and hand-eye coordination. He also keeps a required daily log of his medication’s use and perceived responses.
“Clinical trials are long and hard,” Willison said. “You’ve got to go through hoops, and you’ve got to commit.”
But he has no regrets about taking part in each and every one, adding “I would do them again.”
Still, getting into JEWELFISH was special. Evrysdi, as risdiplam, had already shown solid benefits and safety in young patients, so that he didn’t even consider participation “an experiment.”
“I’m really glad I did this one,” Willison said. “It’s having good effects for me.”
We are sorry that this post was not useful for you!
Let us improve this post!
Tell us how we can improve this post?