MDA 2026: High-dose Spinraza has benefits for many SMA patients
Treatment may help motor function, pooled trial results show
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- High-dose Spinraza benefits SMA patients, stabilizing or improving motor function.
- Pooled trial results show this regimen can enhance motor abilities.
- U.S. regulators are considering approval of the high-dose Spinraza regimen.
A high-dose regimen of Spinraza (nusinersen) that is up for regulatory approval in the U.S. may help stabilize or improve motor function for people with spinal muscular atrophy (SMA), pooled results from two clinical trials show.
“Overall, the improvements observed exceeded what would be expected in a broad population with SMA who have been taking [Spinraza at the standard dosage] for approximately 4 years,” according to a plain-language summary of the results from the drug’s developer, Biogen.
The results involve participants from Part C of the Phase 2/3 DEVOTE clinical trial (NCT04089566), most of whom moved onward to a long-term Phase 3 extension study called ONWARD (NCT04729907). DEVOTE and ONWARD participants who weren’t able to walk (nonambulatory) generally showed the most improvement in motor abilities.
Nancy Kuntz, MD, a neurologist at Lurie Children’s Hospital of Chicago, presented the new analysis at the Muscular Dystrophy Association’s 2026 MDA Clinical & Scientific Conference, held March 8-11 in Orlando, Florida. Her presentation was titled, “DEVOTE Part C and ONWARD Integrated Results: Higher Doses of Nusinersen in Nusinersen-Experienced Participants with Spinal Muscular Atrophy (SMA).” Several co-authors of the study are employees of Biogen, which sponsored the trial.
SMA is caused by mutations in the SMN1 gene. SMN1 contains instructions for cells to produce the survival motor neuron (SMN) protein. SMN supports the nerve cells that control movement. Without enough working SMN, patients develop the characteristic SMA symptoms of muscle weakness and wasting.
Testing higher dosage for those at ‘plateau phase’
Spinraza aims to correct the shortage of functional protein by boosting SMN2 activity. The SMN2 gene is similar to SMN1, but a small difference in the genetic code means that SMN2 produces much less working protein. By binding to SMN2 messenger RNA, a template for protein production, Spinraza increases SMN levels. The therapy is given by injection into the spinal canal.
The approved regimen for Spinraza in the U.S. involves 12 mg doses, first given three times every 2 weeks, followed by a fourth dose a month later, and then doses every four months thereafter. However, people like those who participated in DEVOTE and ONWARD, who had been receiving Spinraza at this dosage for a few years, may stop seeing improvements in motor function.
“We would anticipate that most of the individuals enrolled into DEVOTE or ONWARD would be at a plateau phase,” Kuntz said.
Biogen started DEVOTE to see if increasing the dosage to two 50 mg loading doses given two weeks apart, followed by a 28 mg maintenance dose every four months could provide additional benefits for these patients. Based on the trial results, regulators in the European Union and Japan have approved the high-dose regimen of Spinraza. The U.S. Food and Drug Administration is reviewing a similar regimen, with a decision expected by early April.
The 40 participants in DEVOTE represented a broad range of SMA patients. They ranged in age from 4 to 65, and first experienced symptoms in infancy or later in life. Some could walk, while others could not. They had been receiving Spinraza for a median of 3.9 years before enrolling in the trial. A total of 39 participants continued on this dosage during the ONWARD extension. ONWARD primarily assessed safety, with secondary outcome measures assessing motor function and achievement of motor milestones.
On the Hammersmith Functional Motor Scale-Expanded, a scale that evaluates overall motor function, most participants maintained or improved their score at month 20 of treatment relative to the start of the DEVOTE study. However, patients who needed surgery to correct scoliosis (an abnormal curvature of the spine) showed different trends. “Some of them had a temporary trend down, but prior to this surgery, had been holding even or making small improvements,” Kuntz said.
“Those who actually were nonambulatory without scoliosis made even better increases,” Kuntz added. “They probably had more room for improvement.”
Similarly, on the Revised Upper Limb Module, which tests arm and hand movement, most participants improved or stabilized during treatment. Most ambulatory participants already had the maximum score at study start, the investigator noted.
Less fatigue, more energy
For participants who could walk, the investigators measured how far they could walk in six minutes, another standard motor test. They maintained similar distances over 20 months of treatment, suggesting they weren’t experiencing deterioration. Additionally, throughout the study, they walked similar distances in the first minute and the sixth minute. This may indicate improved endurance.
Several study participants reported feeling less fatigued when taking the higher dosage of Spinraza. “That was just fantastic, from their point of view,” Kuntz said. She said participants told her they were “finishing the full day at work and then still having … energy to breathe at the end of the day,” and one person reported that he was proud to have made it through a weekend bachelor party in Las Vegas.
Biological markers of nerve damage stayed stable throughout treatment. Over 33 months of follow-up, side effects were largely similar to the approved Spinraza regimen, and most were mild or moderate.
“In sum, [high-dose Spinraza] was a very positive experience with good safety and tolerability,” Kuntz said.
Note: The SMA News Today team is providing live coverage of the 2026 MDA Clinical & Scientific Conference March 8-11 in Orlando, Florida. Go here to see the latest stories from the conference.
