• Researchers reviewed four cases in which children with spinal muscular atrophy (SMA) type 1 received onasemnogene abeparvovec-xioi — marketed as Zolgensma — and subsequently started therapy with risdiplam, branded as Evrysdi.
• Treatment was well-tolerated, and all four children experienced improvements in SMA symptoms in the short time they were followed.

Daily doses of risdiplam may provide benefits for children with type 1 spinal muscular atrophy after one-time treatment with onasemnogene abeparvovec-xioi (or onasemnogene). Risdiplam is marketed as Evrysdi, and onasemnogene abeparvovec-xioi is marketed as Zolgensma.

SMA occurs when a mutation to the SMN1 gene limits the production of normal survival motor neuron (SMN) protein. SMN is necessary for normal muscle growth and function. Children with SMA experience progressive muscle weakness that can prevent them from reaching milestones in motor development. The condition also can cause loss of mobility, difficulty eating and talking, and respiratory dysfunction that can lead to death.

Currently, there are only three therapies approved by the U.S. Food and Drug Administration to treat SMA:

• Evrysdi
• Spinraza (nusinersen)
• Zolgensma

Zolgensma is administered as a one-time IV infusion before age 2. Evrysdi is administered daily as an oral solution to people aged 2 months and older.

In a report titled “Combination Therapy With Onasemnogene and Risdiplam in Spinal Muscular Atrophy Type 1” — published in July in Muscle & Nerve — researchers reviewed four cases of children with SMA type 1 treated at Wake Forest Baptist Health Pediatric Muscular Dystrophy Association Clinic in Winston-Salem, North Carolina.

In all four cases reviewed in the study, each child initially showed improvements in SMA symptoms after receiving onasemnogene, then reached a plateau in their improvement. Each child was then started on daily treatment with risdiplam. Two children initially experienced temporary fatigue and minor muscle weakness after starting risdiplam. However, all four children showed continued improvement in SMA symptoms within one month after beginning treatment with risdiplam.

Two of the children in the study were male and two were female. They ranged in age from 17 months to 65 months when assessed for the study. They received their single doses of onasemnogene between the ages of 3 months and 23 months, and they began treatment with risdiplam between the ages of 15 and 58 months.

The researchers note that large, longer-term studies are needed to establish proof that use of both therapies is more effective and still as safe as using one therapy or the other. But this study provides initial indications that therapy with onasemnogene followed by therapy with risdiplam is well-tolerated and may provide benefits to children living with SMA type 1.

Read more about treatments for SMA.