乌鸦传媒

BOSTON -- Upper limb function and walking ability were largely preserved in adults with spinal muscular atrophy (SMA) treated with nusinersen (Spinraza), early results from an ongoing trial indicated.

After 14 months of nusinersen treatment in an open-label, single-arm study , scores for 6-minute walk distance (6MWD), the , and the (RULM) were either stable or showed improvement from baseline, according to Chad Heatwole, MD, MS, of the University of Rochester in New York.

More patients had better function than worse during treatment, and no new safety signals were seen in the study so far, which is intended to run for 30 months, Heatwole told attendees at the American Academy of Neurology's annual meeting here.

Nusinersen was in children and adults in 2016. However, the trials underpinning the approval were conducted exclusively in children; some prospective postmarketing studies have been published but they left some questions unanswered.

Which had been an oversight, because SMA is far from universally fatal in childhood. The disease , designated as types I, II, and III (the latter is also called Kugelberg-Welander disease). While individuals with type I typically don't survive to adulthood, SMA type II is less rapidly progressing and, according to the National Institute of Neurological Disorders and Stroke, patients with type III "can have an average lifespan" with supportive treatment. However, even these patients typically lose function steadily with time, with diminished quality, if not quantity, of life.

In the new study, the investigators focused not on survival but on functional tests, among previously untreated patients at least age 18 years with SMA types II or III. Evaluations also included tests of respiratory function. Patients needing more than 12 hours/day of ventilator support were excluded, as were patients unable to walk who also had very feeble arm or hand function.

Patients were recruited in the U.S. and Canada. The SAS investigators had hoped to enroll 73, with at least 36 in each of two groups (overlap allowed):

• Group 1: ambulatory and non-ambulatory with baseline RULM scores of 4-34
• Group 2: ambulatory with baseline 6MWD at least 10 meters unassisted

In what has become a common refrain recently in research reports, Heatwole said the pandemic interfered with recruitment, and only 43 patients were finally enrolled. These included 32 in group 1 and 14 qualifying for group 2. Mean age was 37, about half were women, and most had two or three copies of the SMN2 gene. Overall, 36 participants completed 14 months of nusinersen treatment, with four switching to a different drug and three lost to follow-up.

In group 1, RULM scores rose an average of 1.0 points (SD 2.4, P=0.02) from baseline through month 14. Group 1's Hammersmith scores, which assess motor function over the entire body, also showed a numerical increase (+0.9 points, SD 4.1, P=0.1).

Group 2, evaluated mainly with the 6MWD, had a mean increase of 11.9 meters (SD 58, P=0.3). Five patients in this group had improvements of 30 meters or more (often considered the minimal clinically important difference), while three had decreases of that magnitude.

A global patient-centered measure of SMA severity, the , also reflected some improvement. Scores across the entire sample with complete data (n=32) decreased a mean of 6.2 points (SD 17.3, P=0.002).

And respiratory function, as measured via forced vital capacity, hardly budged (-0.1 points in percent predicted, P=0.7).

In all, Heatwole said, "most functional outcomes demonstrated stability over 14 months, in contrast to the expected natural history."

Comment