- Novartis' gene therapy Zolgensma helped keep children diagnosed with spinal muscular atrophy prior to symptoms alive and without need of breathing support for 14 months, final data from a trial called SPR1NT show, reinforcing use of the one-time treatment in the youngest patients.
- The small study of children with the degenerative disorder also revealed that most or all participants achieved key motor milestones, including sitting unassisted and standing. Untreated, most children with SMA need breathing support and fail to reach typical motor milestones.
- Zolgensma competes with Biogen's Spinraza, the first-ever therapy for SMA, and Roche's oral Evrysdi. All three won regulatory approvals based on studies of children who already showed symptoms. Newborn screening, however, has necessitated studies in presymptomatic babies to confirm effectiveness in that group of patients.
Newborn screening is now available in 37 U.S. states, covering about 85% of all babies born with SMA, according to Cure SMA, a patient group. In degenerative disorders like SMA, early treatment is more likely to avert disability, so doctors are keen to use the drugs as soon as they make a diagnosis.
Zolgensma, a $2.1 million gene therapy, is a one-time intervention that's designed to delay or prevent disability altogether by replacing a faulty gene and restoring production of a key muscle protein. Because the patients treated to date are so young, it isn't clear whether treatment will be a lasting cure, making monitoring patients' development particularly important.
Rival drugs Spinraza and Evrysdi, by comparison, are give chronically. Spinraza is injected through the spinal column once every four months during maintenance treatment, while Evrysdi is a daily oral medicine.
Novartis is presenting final results from two studies at the European Academy of Neurology virtual meeting this week — the SPR1NT trial in pre-symptomatic babies and the STR1VE-EU study in infants who showed symptoms on average less than two months after birth. All study participants tested positive for a mutation that blocks production of a protein called SMN. In SPR1NT, the babies whose data are being reported had two copies of a backup gene that helps stimulate small amounts of SMN and in STR1VE-EU they had one or two copies.
The 14 babies included in the SPR1NT analysis on average were dosed before the end of their third week of life, and all sat up independently for at least 30 seconds. Eleven did so within the World Health Organization's developmental window, or before they were roughly nine months old.
At 14 months, all were still alive and didn't need breathing support, compared with 26% of untreated patients studied in a previous natural history study, Novartis said.
Roche and Biogen have likewise studied their treatments in babies. In its NURTURE trial, Biogen found treatment with Spingraza before symptoms appeared had long-term benefits for the 25 patients enrolled, all of whom were alive and breathing independently after nearly five years of therapy. Roche's RAINBOWFISH trial has so far returned preliminary data for Evrysdi, with five babies treated for more than one year reaching sitting, rolling and crawling milestones.
STR1VE-EU enrolled severely affected patients, with 23 of the 33 enrolled patients needing breathing support, feeding assistance or both when they entered the trial. Fourteen of 32 in the primary analysis were able to sit unassisted, the main goal of the trial, and a majority met other milestones such as rolling and head control.