Five years of risdiplam: 80% of infants with type 1 SMA alive without permanent ventilation

Design

Open-label phase 2 trial with 3-year extension (FIREFISH)

Population

62 infants aged 1–7 months with type 1 SMA and two SMN2 copies

Primary outcome

Long-term safety, survival, event-free survival and motor milestones at 5 years

Effect

Alive 90%; alive without permanent ventilation 80%; sitting ≥30 s 59%

FIREFISH enrolled 62 infants aged 1–7 months with type 1 spinal muscular atrophy and two SMN2 copies in an open-label phase 2 trial of oral risdiplam; 55 continued into a three-year extension, and results at five years were published in July 2026.

At five years, 90% were alive and 80% alive without permanent ventilation. In the pivotal-dose group, 59% could sit unsupported for 30 seconds, 7% could stand unsupported and none walked independently. Mean CHOP-INTEND scores rose from about 22 to about 50. Most kept oral feeding (72%) and swallowing (79%). Pneumonia was the commonest serious adverse event (45%). No new safety concerns emerged.

Without treatment, most infants with type 1 SMA die or need permanent ventilation within two years, so these are large gains. But there was no control group, and the children still carry major disability. Early diagnosis — ideally by newborn screening before symptoms — remains the biggest lever.

• Suspect SMA in any floppy infant with weak cry, poor feeding or paradoxical breathing and refer urgently.
• Treatment is time-critical; the earlier it starts, the better the motor outcome.
• Expect continuing needs: respiratory support, feeding assessment and physiotherapy.
• Pneumonia remains common — vaccinate fully and have a low threshold for review in respiratory illness.

Why it matters

It shows that an oral, home-given drug sustains survival gains in a disease that was almost uniformly fatal.

Don't overread it

An uncontrolled, company-funded extension of 62 infants — compared with natural history, not a randomised arm.

The statistics, in plain English

With 58 children in the pivotal-dose group, each child is about 1.7 percentage points, so small differences in milestone rates are not meaningful.

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