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S129: The Comparison of AAV Gene Therapy Products, Onasemnogene Abeparvovec and Resamirigene Bilparvovec, in Pediatric Patients

Poster Presenter

Prabjyot Jhatu

Student
Chicago State University
United States

Objectives

The study was to compare the similarities and differences between adeno-associated virus vector-based gene therapy products, specifically onasemnogene abeparvovec and resamirigene bilparvovec, to address safety concerns in pediatric patients and considerations for future clinical trials.

Method

The tools used for this study were a collection of published information, including product labeling, literature reports, and clinical trials Aspiro and Gene Transfer for SMA Type 1, regarding the safety and efficacy of gene therapy products for a pediatric population.

Results

The analyzed information indicates that there were similarities and differences noticed in the pediatric patients that experienced adverse events while being dosed with both of the gene therapy products. The primary similarity is that all fatalities in both patient populations occurred from liver failure due to hepatotoxicity. The main differences that were observed in the fatalities reported were the number of deaths, age range, dosing, and time of death post-infusion, of each medication population. In the post-market, the two patients that died after receiving onasemnogene abeparvovec were less than 2 years of age. The dosing these patients received were 2.0 x 10^13 vg/ml based off weight. The time of death that was reported post-infusion was 6-7 weeks in each case. Conversely, all 4 male patients in the Aspiro clincal trial that experienced death post resamirigene bilparvovec infusion were less than 5 years of age. The dosing that 3 out 4 patients received were 3.5 x 10^4 vg/kg based off weight. The 4th patient who died had received the lower dose 1.3 x 10^14 vg/kg and death is still pending. After the 3 initial deaths, the FDA placed the clinical trial on hold. The 4th patient was the first and only patient who received a dose of resamirigene bilparvovec after the hold was lifted. This death occurred in 2021 and the trial is still on hold. However, all 4 patients had a post-infusion time of death of 3-4 weeks.

Conclusion

The benefits vs. risk outcomes must be considered before administering gene therapy products. The indication of onasemnogene abeparvovec is SMA in patients less than 2 years of age. The life expectancy of patients diagnosed with SMA is less than 2 years. Alternatively, resamirigne bilparvovec in the Aspiro clinical trial is indicated in male patients diagnosed with XLMTM in patients less than 5 years of age. The life expectancy for XLMTM is also less than 2 years. The potential benefit that these medications have is to increase the patient life expectancy. Similarly, the risks associated with both gene therapy products are elevated liver enzymes leading to hepatoxicity and ultimately death. After a full review, this information should be used to create stricter guidelines when recruiting patients for future drug regiments. This can be seen by implementing more specific restrictions to the inclusion and exclusion criteria prior to dosing and addressing potential toxicities, proactively. Further assessments to adjust and advance carefully need to be done in these disease states to determine whether any underlying conditions associated with these genetic disorders are contributing to the drug-related adverse events.