Taysha’s promising gene therapy results marred by patient death – PharmaLive

Shares of Taysha Gene Therapies are down more than 10% after a the death of the patient tainted positive provisional data for the Company’s investigational gene therapy treatment for Sandhoff and Tay-Sachs disease, which are two forms of GM2 gangliosidosis.

Texas-based Taysha’s first TSHA-101-treated patient has been diagnosed with Sandhoff’s disease, a rare inherited condition that progressively destroys nerve cells in the brain and spinal cord. After administering TSHA-101, an experimental gene therapy that delivers both the HEXA and HEXB genes that make up the β-hexosaminidase A enzyme, the patient demonstrated clinical improvement after three months. The patient was allowed to go home. However, Taysha said the unvaccinated patient had been exposed to a family member who was symptomatic of an upper respiratory infection, which was likely COVID-19. Taysha’s patient was hospitalized with pneumonia. While there, the patient contracted a secondary hospital-acquired methicillin-resistant staphylococcus aureus (MRSA) infection and ultimately succumbed.

Trial investigators initially assessed that the patient’s death was unlikely to be due to the gene therapy. However, according to the company, a review by the independent Data Safety Monitoring Board is ongoing and the results are expected in the short term.

Prior to the patient’s death, Taysha said his disease had achieved normalization of Hex A enzyme activity by the end of the first month following gene therapy treatment. The levels were “58 times higher than the presumed asymptomatic level of 5% of normal identified by natural history at month 3,” the company said. Based on available data, the patient achieved Hex A enzyme activity of 190% and 288% of normal at month 1 and month 3, respectively.

The second patient to receive gene therapy is a Tay-Sachs patient. Another rare genetic disorder, Tay-Sachs is caused by the lack of an enzyme that helps break down fatty substances called gangliosides. Without the ability to break them down, gangliosides build up to toxic levels in the brain and spinal cord, leading to premature death.

After administration of TSHA-101, patient Tay-Sachs achieved a Hex A enzyme activity of 25% of normal at month 1. These data represent a 5-fold improvement above the assumed asymptomatic level of 5% of normal identified by natural history.

Source: Organic Space

Despite the early death which is possibly related to COVID-19, Taysha said the data for TSHA-101 is the “first to support the bicistronic vector approach in humans delivering both HEXA and HEXB genes in endogenous relationship. Although the patient’s cause of death is still under investigation, the company said preliminary data suggests that TSHA-101 was well tolerated with no significant drug-related events.

TSHA-101 is the only bicistronic vector currently in clinical development for GM2 gangliosidosis and has received orphan drug and rare pediatric disease designations from the United States Food and Drug Administration. It has also received orphan drug designation from the European Commission.

“TSHA-101 is the first bicistronic vector in clinical development, which represents an important first in the field of gene therapy,” said RA Session II, President, Founder and CEO of Taysha, in a statement. “TSHA-101 demonstrated expression of HEXA and HEXB genes in the endogenous ratio, providing the ability to restore and normalize enzyme activity in GM2 gangliosidosis. We plan to provide ongoing updates on the program, with additional clinical data expected by the end of 2022.”

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