Real-World Italian Survey Study Provides Insight on SMA Prevalence in Age of New Therapeutics

Eugenio Mercuri, MD, PhD

Recently published data in Neurology provided insight on the prevalence of spinal muscular atrophy (SMA) at a national level and the current distribution of patients treated with therapeutic options, which started to come into the space in 2016.¹

Overall, 1255 patients with the disease were currently followed in Italian centers with an estimated prevalence of 2.12/100,000. This value was higher than that (1.81; 95% CI, 0.010-0.026) recorded in 2016 by the Institutional National Registry of Rare Diseases of the ISS.

The SMA treatment paradigm has shifted drastically in the past few years with the approval of 3 treatments: nusinersen (Spinraza; Biogen), onasemnogene abeparvovec (Zolgensma; Avexis), and risdiplam (Evrysdi; Genentech/Roche). Each of these therapies is different. Nusinersen, an antisense oligonucleotide, increases the amount of SMN protein from SMN2, and is approved for all types of SMA. Zolgensma, a gene replacement therapy, also increases SMN protein but from SMN1. It is currently FDA-approved for patients aged less than 2 years old and in type 1 for up to 3 SMN2 copies. Risdiplam, a small molecule agent, is similar to nusinersen in that it increases SMN protein from SMN2; however, it is approved for all SMA types and infants less than 2 months old.

Led by Eugenio Mercuri, MD, PhD, professor of pediatric neurology, Catholic University Rome, the analysis aimed to assess the prevalence of SMA and treatment prescription in Italy. Thus, an online survey was distributed to 36 referral centers with additional data subdivided according to age, type, SMN2 copy number, and treatment. Survey completion rate was 100%, and period prevalence was calculated as the proportions of patients affected by SMA in 1 year divided by the Italian population at 2021 (59,258,000 persons).

Among the 1255 patients with 5qSMA, 604 were adults and 650 were children, with SMN2 copies available in slightly more than three-fourths of the identified group (77.45%). The 2 most highly prevalent types were type 2 and 3, which included 470 and 467 patients, respectively, for an estimated prevalence of 0.79/100,000. Of those with type 2, 400 (85%) were treated with new therapies. For the type 3 cohort, 369 (79%) were treated with new therapies. Of these two groups, nusinersen was the most used treatment, representing 40.75% of type 2 and 68.74% of patients with type 3. Patients on therapies in clinical trials accounted for 22.25% of type 2 patients and 5.35% of type 3 patients.

The type 1 population was the least of the 3, and included 284 patients for an estimated prevalence of 0.48/100,000. Of the 284, 272 were treated with new therapies. Nusinersen was once again the most used treatment (46.69%), followed by clinical trials (20.59%), Zolgensma (18.75%), and risdiplam (13.97%).

"The high number of patients currently treated with nusinersen largely reflects the fact that this was the first drug to be approved and the only available option for over three years,” Mercuri et al wrote.¹ "At the time of the survey Risdiplam was only available for compassionate use and onasemnogene abeparvovec could only be prescribed to type I infants younger than two years and with a weight below 13.5 Kgs. The percentage of treated patients decreased with decreasing severity. Further follow up will allow to establish how these numbers will change with the recent commercial availability of Risdiplam."

REFERENCES
1. Coratti G, Ricci M, Capasso A, et al. Prevalence of spinal muscular atrophy in the era of disease-modifying therapies: an Italian nationwide survey. Neurology. Published online December 2, 2022. doi:10.1212/WNL.000000000000201654.