New certification: After 24 months of Risdiplam treatment, 61% of children with type 1 SMA achieved unsupported sitting alone | AAN 2021

Guide ➤After 24 months of treatment, the proportion of children who were assessed by BSID-III to sit alone for at least 5 seconds without support was twice as high as that at 12 months (61% vs 29%); ➤Risdiplam improved the survival rate of children.
Reduce the need for permanent ventilation; ➤Risdiplam's effectiveness for adults, children, and children over 2 months of age has been proven.

On April 17-22, 2021, the 73rd American Academy of Neurology (AAN) will be held online as scheduled.
AAN is committed to promoting high-quality patient-centered neurological care.

This annual conference covered 90+ expert-led training courses, more than 2,000 scientific abstracts, and 7 plenary meetings attended by neurology leaders to discuss and exchange the most cutting-edge scientific research.

At this conference, the second part of the FIREFISH study, the effectiveness and safety data results of Risdiplam in the treatment of type 1 spinal muscular atrophy (SMA) in children for 24 months was announced.

Study Introduction The FIREFISH study is one of the four international multi-center clinical studies carried out by Risdiplam around the world.
It was carried out in children with type 1 SMA who are 1-7 months old and have 2 copies of the SMN2 gene.
It is divided into 2 parts ( figure 1).

The median total CHOP INTEND score at baseline of the enrolled patients was 22.
0 (8.
0-37.
0), and the median total HINE-2 score was 1.
0 (0.
0-5.
0).

 The primary endpoint of the study was the proportion of children who were sitting alone without support for ≥5 seconds.

Other key outcomes include: the proportion of children sitting alone without support for ≥30 seconds, the proportion of children with a total CHOP INTEND score of ≥40, the achievement of exercise milestones assessed by HINE-2, the proportion of children who survived without permanent ventilation, Proportion of children who can swallow and feed orally, number of hospitalizations/patient year.

Figure 1 FIREFISH study design The 12-month data of the second part of the FIREFISH study has been announced at the European Academy of Neurology (EAN) in 2020.

This year’s AAN released the 24-month data for the second part of the FIREFISH study.

 Study Results The 24-month results of the second part of the FIREFISH study showed that after Risdiplam treatment, the patient's ability to sit alone without support continued to improve.

Among them, 61% (25/41) of children sitting alone without support for ≥5 seconds; 44% (18/41) of children sitting alone without support for ≥30 seconds (Figure 2).

In contrast, untreated children with type 1 SMA cannot achieve unsupported sitting alone.

 Figure 2 After Risdiplam treatment, the ability of SMA patients to sit alone without support continued to improve.
The total CHOP INTEND score of SMA patients continued to increase.
At 24 months, the total CHOP INTEND score ≥40 accounted for 76% of children (Figure 3).

At 12 months, the median value of CHOP INTEND total score improved from baseline was 20 points; at 24 months, the median value of CHOP INTEND total score improved from baseline was 27 points.

In contrast, in the natural history of SMA disease, children with type 1 SMA rarely achieve a total CHOP INTEND score of 40.

 Figure 3 The CHOP INTEND total score of SMA patients continued to increase after Risdiplam treatment.
When evaluated using the HINE-2 scale and pre-established response criteria, 85% (35/41) of the children responded to the treatment; during 12-24 months , The patient continues to achieve sports milestones (Figure 4).

Figure 4 Percentage of children with SMA who achieved exercise milestones.
The time to event-free survival of patients increased.
93% (38/41) of children survived, and 83% (34/41) of children achieved event-free survival (no permanent Ventilation). In contrast, in the natural history of SMA disease, the median age at which patients died or required permanent ventilation was 10.
5 (8.
1-13.
6) months (Figure 5).

Figure 5 After Risdiplam treatment, the event-free survival rate of SMA patients was significantly improved.
Among patients who survived, 95% (36/38) maintained the ability to swallow; 92% (35/38) could achieve oral feeding, which was an increase compared to 12 months 1 patient.

In contrast, in the natural history of SMA disease, children over 12 months of age require feeding support.

 At 24 months, 34% (14/41) of the patients did not need to be hospitalized.

For patients who had hospitalizations, the number of hospitalizations was reduced by half during the 12-24 month period; the number of hospitalizations during the 12-month period was 1.
3 per patient year, and the number of hospitalizations during the 24-month period was 0.
94 per patient year.

In contrast, in the natural history of SMA disease, the number of hospitalizations is ~4.
2-7.
6/patient-year.

In addition, there was no discontinuation of treatment or withdrawal from the trial due to drug-related adverse events.

 Summary FIREFISH study Part 2 of the 24-month results compared with the 12-month results, the effectiveness continues to improve, and the safety is still good.

Studies have shown that Risdiplam is very effective for children with type 1 SMA.

In addition, the FIREFISH study will continue for 5 years, and we will continue to report on it, so stay tuned.

Reference: BT Darras, R Masson.
et.
al.
ANN 2021.
FIREFISH Part2: 24-month efficacy and safety of risdiplam in infants with Type 1 spinal muscular atrophy(SMA).
Source: SMA New Voice