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BOSTON -- Older children with spinal muscular atrophy (SMA) Types 2 and 3 achieved greater improvements in motor function with nusinersen (Spinraza) compared with a sham injection, but the benefits of the drug may be greatest when given earlier, researchers reported here.

In the full analysis from the CHERISH study, children ages 2 to 12 had a significantly greater improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE) with nusinersen than with placebo over 15 months (mean difference 4.9 points, P=0.0000001), Eugenio Mercuri, MD, of the Catholic University of the Sacred Heart in Rome, and colleagues reported during an emerging science session here at the .

Mercuri noted that the drug was well-tolerated and had no major safety issues.

But experts at the meeting were quick to point out that motor milestones were more frequently achieved in two studies involving infants -- ENDEAR and NURTURE -- and the best results were seen in those who were pre-symptomatic when they started on the drug.

"Children captured later also benefit, but there's evidence that they do better when they're treated early," Natalia Rost, MD, of Massachusetts General Hospital, who wasn't involved in the study, said during a press briefing. "The argument is that the later you catch the disease, the less chance you have of affecting functional outcomes."

The phase III CHERISH trial enrolled 126 children with later-onset SMA, typically Types 2 and 3, randomizing them to a sham procedure or to 4 doses of intrathecal nusinersen (12 mg nonscaled) during a 15-month study. Nusinersen is an antisense oligonucleotide that restores production of a full-length SMN protein, which is affected by a mutation in the namesake gene.

In previously reported interim results, patients on nusinersen had greater improvement on the HFMSE than those on placebo (a mean increase of 5.9 points compared with a mean decline of 1.9 points, P=0.0000002).

Final results of the study tracked well with those earlier results, with a mean difference of 4.9 points between groups at 15 months (3.9-point improvement versus 1-point decline, P=0.0000001).

Drug-treated patients also saw better results on the secondary endpoint of the proportion of responders on the HFMSE (56.8% versus 26.3%, P=0.0006), and they had better improvements in revised upper limb module (RULM) score (4.2-point improvement versus 0.5-point improvement, P=0.0000001).

There was a trend toward greater achievement of any new WHO motor milestone in the nusinersen group, but it wasn't significant, Mercuri reported (19.7% versus 5.9%, P=0.08).

He said the drug showed good safety, although there was more back pain, headache, and vomiting in the drug-treated group, which he said was likely due to the injection.

"The CHERISH study confirms what we had seen in the infant studies, that patients on nusinersen had statistically significant and clinically significant improvement in motor function when compared to children treated with a sham procedure," Mercuri said. "We also confirmed the tolerable safety profile, as the majority of adverse events were related to the disease, as they were found in the placebo group, or they were related to the lumbar puncture."

He added that all CHERISH participants are still being followed in the SHINE open-label cohort.

Rost said that between nusinersen and an early-stage gene therapy for SMA Type 1, "neuromuscular disease is making a breakthrough that's desperately needed" -- but at a cost.

"The costs are exuberant, there is no question about that," Rost said, noting the drug's $125,000 price tag per injection, which adds up to about $750,000 for the first year and $375,000 each year thereafter.

"Everything has a price, and in this case, it is priceless -- it extends life. That's very different from preventing one day of migraine," she said. "Nevertheless, it's extremely expensive."

She added that the long-term benefits and safety of the drug are not yet known, and it's unclear just how much longer children with SMA will live by taking these new drugs.

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