The findings, which are significant compared with the disease’s natural history, need to be further confirmed in larger real-world studies, the researcher said.
The study, “Safety and Treatment Effects of Nusinersen in Longstanding Adult 5q-SMA Type 3 – A Prospective Observational Study,” was published in the Journal of Neuromuscular Diseases.
SMA comprises a group of neurodegenerative disorders characterized by the gradual loss of motor neurons — the nerve cells responsible for controlling voluntary muscles — leading to muscle weakness and wasting.
Type 3 SMA is a late-onset, and generally milder form of the disease. In these patients, the symptoms become apparent between 18 months and 12 years of age, but individuals are able to stand and walk at least for some time in life.
Biogen’s Spinraza in December 2016 became the first approved treatment indicated for SMA types 1–3 in children and adults in the U.S. This was followed by approval in other countries, including Australia, Brazil, Japan, Switzerland, South Korea, Canada, Chile, and several other countries in Europe.
While Spinraza’s therapeutic effects have been widely demonstrated in earlier stages of the disease and in young patients, there is no data from clinical trials or real-world studies on its efficacy in adults with SMA type 3.
“Until now, it remains unclear which outcome measures are most suitable in adult patients for assessment of treatment effects,” the researchers said.
The prospective, observational, real-world study evaluated the safety and effectiveness of Spinraza in 19 adults in Germany with longstanding SMA type 3.
Participants received Spinraza intrathecally — injected directly into the spinal canal — at day 1 (baseline), day 14 (visit 2), day 28 (visit 3) and day 63 (visit 4). They also received the medication as part of maintenance treatment at day 180 (visit 5) and day 300 (visit 6) which was 10 months after the study’s start. Clinical data was collected at baseline, visit 4, visit 5, and visit 6.
The patients’ muscle function was measured using the Medical Research Council (MRC) Muscle scale. Assessments of motor function included the Hammersmith Functional Motor Scale Expanded (HFMSE) scores, 6-minute walk test (6MWT) results, Revised Upper Limb Module (RULM) measures, and ALS Functional Rating Scale (ALSFRS-R) scores.
Lung function was evaluated through forced vital capacity (FVC) — the total volume of air that can be blown forcefully following a full inhalation — and cough peak flow, a measure of cough strength.
Participants ranged in age from 18 to 59 years, and had a median age at disease onset of 12 years; their median disease duration was 23.8 years. Seven patients were women and 12 were men. Among the participants, 12 (63%) were able to walk, and seven (37%) were wheelchair-dependent. A total 17 of the 19 participants completed the observation period of 10 months (visit 6).
Longer disease duration was associated with poor motor function, supporting assumptions that “an early start of treatment may be beneficial by decelerating the progression of muscle weakness,” the researchers said.
Treatment with Spinraza led to mild improvement or stabilization of motor and lung function in these patients. Statistically significant improvements were observed in the 6MWT at visits 5 and 6 — with seven ambulatory patients achieving an improvement between 31 and 83 meters — RULM at visit 5, and in peak cough flow at visit 5.
While the effects of these changes were not considered clinically meaningful, “stabilization or even improvement [in motor and lung] function tests over such a short period of time is significant,” the researchers said.
“Improvement of 6MWT in SMA natural history cohorts has never been described so far, and no training effect has ever been described in natural history,” they said.
Although non-significant statistically, nine participants also showed improvements in the Hammersmith HFSME score, with five increasing their scores by more than 3 points — which is considered clinically meaningful.
Spinraza was generally well-tolerated, with no reports of serious adverse events. A total of seven patients reported back pain and four reported headache following Spinraza administration — a total of 11 times on 108 administrations (10%).
“Even in [SMA type 3] patients with a long-standing disease course up to 53 years and a median disease duration of 24 years, improvement of motor function exceeded our expectations of mere disease stabilization, justifying treatment beyond childhood and early adolescence,” the researchers concluded.
The team noted that their findings suggested that the 6MWT and the HFMSE score might be sensitive enough to assess changes in disease progression in SMA type 3 adults.
Future real-world studies in larger groups of patients are required to better understand the clinically meaningful effects of Spinraza in adults with SMA type 3, the investigators said.