This European study included patients with more severe cases of spinal muscular atrophy than a similar study conducted in the United States.
Zolgensma (onasemnogene abeparvovec-xioi) shows efficacy in patients with severe spinal muscular atrophy (SMA), according to results recently published in The Lancet Neurology.
The results of a phase 3 study called STR1VE-UE confirmed the safety and efficacy results of the Phase 1 START and Phase 3 STR1VE-US studies. The study, funded by Novartis, the manufacturer of Zolgensma, showed that patients under six months of age with type 1 SMA experienced therapeutic benefits with a single administration of gene therapy.
A treatment for Zolgensma costs more than $ 2 million, and Zolgensma is often identified as the most expensive drug treatment of all time.
SMA is a rare, genetic disease which affects the central nervous system, peripheral nervous system and muscle movements. It is caused by a genetic defect in the survival motor neuron (SMN) 1 gene which encodes the SMN protein, which is necessary for the survival of motor neurons. The incidence of SMA is approximately 1 in 10,000 live births, and it is the leading genetic cause of infant mortality. The most severe form of SMA is type 1.
Zolgensma was approved by the FDA in May 2019 for patients under two years of age with mutations in the SMN1 gene. The therapy provides a functional copy of the gene in a single, single infusion. In the USA phase 3 trial of 22 patients with type 1 SMA, 13 infants sat independently for 30 seconds or more by 18 months of age.
STR1VE-EU is a single-arm phase 3 trial performed at nine sites in Italy, UK, Belgium and France. The researchers recruited patients under 6 months of age with type 1 spinal muscular atrophy with exon 7-8 deletion of SMN1 or point mutations, and one or two copies of SMN2. Thirty-two of the 33 patients completed the study.
Investigators reported in Lancet Neurology that they found that 14 of 32 patients achieved the primary endpoint of independent functional sitting for at least 10 seconds during any visit up to the age of 18 months, which is an important milestone in the WHO development for independent sitting. None of the 23 patients in a matched, untreated natural history cohort reached this endpoint.
In addition, 31 of the 32 patients who received Zolgensma survived without permanent ventilatory support to 14 months.
Improvements in motor function were assessed for safety and efficacy using predefined exploratory motor parameters. Twenty-seven of 33 patients achieved at least one motor milestone during the study. Investigators found that 3 patients gained head control and 19 patients rolled back to their sides. Additionally, 16 patients sat unsupported for 30 seconds or more.
Almost all of the patients in the EU trial had at least one adverse event and six patients had adverse events considered serious and treatment-related. The most common adverse events were fever (22 patients), upper respiratory tract infections (11) and increased alanine aminotransferase (nine).
âSTR1VE-EU showed the efficacy of onasemnogene abeparvovec, with greater variability in response to efficacy than in STR1VE-US due to the differences in the clinical status of patients at baseline. Some of these patients presented with an early onset and more severe disease at the time of inclusion than the STR1VE -US patients, but showed a response to treatment not only in terms of survival but also functional aspects â, have writes the investigators.