Use of the antisense oligonucleotide nusinersen (Spinraza,
Biogen/Ionis Pharmaceuticals) appears effective and tolerable for the treatment
of children with symptomatic spinal muscular atrophy (SMA), new research
suggests.
The phase 3 CHERISH trial, which included 126 participants
with SMA aged 2 to 12 years, met its
primary outcome measure. It showed that those who received 4 doses of
intrathecal nusinersen over 9 months had significantly greater improvement in
Hammersmith Functional Motor Scale-Expanded (HFMSE) scores compared with those
who received a sham procedure.
In addition, the active treatment group had more
improvements in upper-limb function and a greater number of new motor
milestones achieved. No child stopped treatment because of adverse events
(AEs).
As reported by Medscape Medical News, the US Food and Drug
Administration approved nusinersen in December 2016, marking the agency's first
approval for an SMA drug. And last week, the European Medicines Agency
Committee for Medicinal Products for Human Use recommended approval based on
the findings from CHERISH and from the positive ENDEAR trial, which assessed
infantile-onset SMA.
"Nusinersen had significant and clinically meaningful
improvements compared with the sham procedure control-treated children, while
demonstrating a favorable safety profile," said Eugenio Mercuri, MD, PhD,
associate professor in pediatric neurology at Universita Cattolica del Sacro
Cuore in Rome, Italy.
He presented the findings at an Emerging Science session
here at the American Academy of Neurology 2017 Annual Meeting (AAN).
Nusinersen "alters SMN2 gene splicing to promote the
production of full-length SMN protein," write the investigators.
In CHERISH, they enrolled children with confirmed 5q SMA who
had symptom onset after age 6 months. All were randomly assigned 2:1 to 4 doses
of 12 mg nonscaled intrathecal nusinersen (n = 84) or a matching sham procedure
(n = 42) over 9 months during the study's 15-month duration.
In the active treatment and sham procedure groups, 55% vs
50%, respectively, were girls; the mean age at screening was 4 vs 3 years; and
the mean age at symptom onset was 10 vs 11 months.
In addition to 15-month evaluation, prespecified interim
analysis for the primary endpoint was conducted.
Key secondary outcomes included percentage of children who
were HFSME responders, defined as an increase of 3 or more points on the
measure between baseline and month 15, and changes in scores on the revised
Upper Limb Module (RULM).
Results showed that the group receiving nusinersen had
highly significantly greater changes on the HFMSE and RULM than the sham
procedure group, with more members becoming HFMSE responders (adjusted odds
ratio for the latter outcome, 5.59; 95% confidence interval, 2.09 - 14.91).
Although a greater percentage of the active treatment group
achieved any new World Health Organization (WHO) motor milestones (19.7% vs
5.9%), this missed statistical significance (P = .08).
However, the number of new WHO milestones achieved per child
was significantly higher in those receiving nusinersen (0.2 vs –0.2; P = .0001).
In addition, 1.5% were able to walk without assistance at the end of the study
compared with none of the children who received the sham procedure.
Interestingly, the control group had more reports of any AE,
severe AE, or serious AE than did the active treatment group (100% vs 93%, 55%
vs 46%, and 17% vs 29%, respectively).
AEs possibly related to the study drug were reported by 29%
of those receiving nusinersen and 10% of those receiving the sham procedure.
The most frequently reported AEs were pyrexia (by 43% vs 36%), upper
respiratory tract infection (30% vs 45%), headache (29% vs 7%), and vomiting
(29% vs 12%).
"The majority of AEs were considered to be related to
SMA disease, common events in the general population, or events related to the
lumbar puncture procedure," said Dr Mercuri.
He noted that the study population will now be transitioned
into the SHINE open-label extension trial.
No comments:
Post a Comment