AveXis, a gene therapy company, presented interim data from the ongoing phase 1 clinical trial of AVXS-101 in Spinal Muscular Atrophy Type 1, at the International Annual Congress of the World Muscle Society in Granada, Spain.
AVXS-101 aims to replace the SMN1 gene, which is missing or defective in SMA. This gene codes for a protein called SMN, which is crucial for the survival of motor neurons, the cells which control muscle activity. Without enough of this protein, these cells die and the muscles are no longer told to contract and relax. To read about gene replacement in SMA, please read click on this link.
The data, presented by Dr. Jerry Mendell, M.D., director of the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital, showed that the majority of patients on the proposed therapeutic dose achieved key developmental milestones, including sitting unassisted and two patients walking independently.
For the first time, interim data from the trial were presented that highlighted patient achievement of key motor development milestones as of September 15, 2016:
- Two-thirds of patients in Cohort 2 (the proposed therapeutic dose) had achieved the ability to sit unassisted, including one patient whose achievement of this milestone was confirmed after September 15.
- In Cohort 2, 11 of 12 patients achieved head control, 7 of 12 patients could roll over completely and 11 of 12 patients could sit with support.
- Two patients are now walking independently, including one whose achievement of this milestone was confirmed after September 15. These two patients each achieved earlier and important developmental milestones such as crawling, standing with support, standing alone and walking with support.
“To date, the majority of patients who received the proposed therapeutic dose of AVXS-101 have achieved key milestones and two-thirds of these patients can sit independently – a fact completely inconsistent with the known disease course, as children with untreated SMA Type 1 will never sit unassisted,” said Sean Nolan, President and Chief Executive Officer, AveXis. “We are encouraged by these interim data, and continue to work diligently to bring this gene therapy to the children suffering from this devastating condition.”
Phase 1 Interim Data as of 15th September 2016
- AVXS-101 continued to demonstrate a favourable safety profile and was generally well tolerated, with no new treatment-related safety or tolerability concerns identified.
- There has been a cumulative total of 118 adverse events (AEs) reported as of September 15, 2016, 34 of which were determined to be serious adverse events (SAEs) and 84 were determined to be non-serious AEs. As previously reported, a total of 5 AEs in 4 patients were treatment-related. Two were deemed treatment-related SAEs (experienced by 2 patients) and three were deemed non-serious AEs (experienced by 3 patients). All consisted of clinically asymptomatic liver enzyme elevations.
- All of the elevated liver enzyme AEs and SAEs were clinically asymptomatic and resolved with prednisolone treatment. There were no clinically significant elevations of gamma-glutamyl transferase (GGT), alkaline phosphatase or bilirubin, and as such Hy’s Law was not met. Other non-treatment-related AEs were expected and were associated with SMA.
- All patients in Cohort 2 (proposed therapeutic dose) are event-free, defined as death or requiring at least 16 hours per day of ventilation support for breathing for greater than two weeks in the absence of an acute reversible illness, or peri-operatively. The median age at last follow-up for Cohort 2 is 17.3 months, with the oldest patient at 27.4 months of age.
- As previously reported, one patient in Cohort 1 (the low-dose cohort) did have a pulmonary event after July 1, 2016. The patient had increased use of bi-level positive airway pressure (BiPAP) in advance of surgery related to hypersalivation, a condition experienced by some SMA patients; the event was determined by independent review to represent progression of disease and not to be related to the use of AVXS-101.
- Mean increases in CHOP-INTEND scores of 9.0 points in Cohort 1 and 24.8 points in Cohort 2 were observed, reflecting improvement in motor function. The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) is a test developed to measure motor skills of patients with SMA Type 1.
- 11 out of 12 patients in Cohort 2 achieved CHOP-INTEND scores of at least 40 points.
- 9 out of 12 patients in Cohort 2 achieved CHOP-INTEND scores of at least 50 points.
- 3 out of 12 patients in Cohort 2 achieved CHOP-INTEND scores of at least 60, which is in a range considered to be normal.
- Patients on the proposed therapeutic dose of AVXS-101 consistently achieved and maintained key developmental motor milestones:
- As of September 15, 2016, 11 out of 12 patients achieved head control;
- 7 out of 12 patients could roll over (completely);
- 11 out of 12 patients could sit with support; and 8 out of 12 patients could sit unassisted, including one patient whose achievement of this milestone was confirmed after September 15.
- 7 patients are able to feed themselves, including one patient whose achievement of this milestone was confirmed after September 15 and 5 patients are speaking (1 bilingual).
- 4 patients are now standing with support, including two whose achievements of this milestone were confirmed after September 15.
- 2 patients are now walking independently, including one whose achievement of this milestone was confirmed after September 15. These two patients each achieved earlier and important developmental milestones such as crawling, standing with support, standing alone and walking with support.
“The preliminary clinical observations of extended event-free survival, sustained increases in motor function and achievement of developmental milestones in patients receiving a one-time infusion of AVXS-101 have far exceeded what has been observed with natural history,” said Suku Nagendran, MD, Senior Vice President and Chief Medical Officer, AveXis. “These preliminary results demonstrate the potential of AVXS-101 to positively impact quality of life and as such alter the course of disease in these children with SMA Type 1.”
For more detailed information on the data, please see Avexis’ press release dated 8th October 2016.