Two Food Drug Administration (FDA) approved gene modifying therapies (nusinersen and zolgensma) are currently available for SMA. Prior to FDA approval, AVXS-101 (zolgensma) was available for patients through physician initiated single patient investigational new drug and managed access program.  Data on experience of combination gene modifying therapies in patients with SMA is lacking.

We describe 3 cases of SMA 1 (2 copies of SMN2) who received both nusinersen and AVXS-101. Case 1 was diagnosed at 6 months of age and started nusinersen a month later. Case 2 was started on nusinersen immediately after diagnosis at 1.5 months. Both showed improvements with nusinersen. They received AVXS-101 at 21 (9.5 Kg) and 18 months (10.5 kg) of age respectively and continued to show improvements. Nusinersen was continued on both patients. Mild elevation of liver enzymes was noted after AVXS-101 treated with prophylactic oral steroids. Significant elevation of liver enzymes noted in both patients after thy received subsequent nusinersen maintenance doses. This resulted in hospitalization, liver biopsy, intravenous corticosteroids, and prolonged oral steroid treatment for case 2 and prolonged oral steroid for case 1. Case 3 was diagnosed at 5 months and received AVXS-101 at 6 months of age. Nusinersen was started at 9 months as there was no improvement after AVXS-101. Patient remains alive and stable at 15 months of age.

These cases illustrate the clinical experience of combination gene therapy for SMA 1. Prolonged period of liver enzymes elevation and steroid treatment can be seen. Case 3 reiterates that better outcomes are seen with early AVXS-101 treatment. Worsening liver function may be related to combination therapy. Further data will be presented at the meeting.