Guggenheim Grand Rounds: Expert Call on Rett Syndrome - How Will the Market Shake Up Between NGNE & TSHA

Research evidence excerpt

Guggenheim Grand Rounds: Expert Call on Rett Syndrome - How Will the Market Shake Up Between NGNE & TSHA

set or worsened seizures, or

increased winter respiratory infection susceptibility (the latter being characteristic of MECP2

duplication syndrome). To date, he has seen no such signal from either program. Overall,

Dr. Lieberman expects that 12 months of follow up will likely not be sufficient to determine

any potential efficacy differences between NGNE and TSHA.

Per Dr. Lieberman, age effects in Rett may be as much societal as biological

Patients aged 22 and older typically lose school-district-provided PT/OT/speech support,

with insurance coverage of post-graduation therapy varying widely, which may attenuate

observable post-treatment gains in older patients independent of any underlying biological

ceiling. He does not view the biology of a 20-year-old as materially different from that of a

teenager and would not differentiate his clinical decision-making between a 4-year-old and

a 7-year-old based on the age cohorts in pivotal data. He flagged that regression in Rett is

not always linear or complete by age 3, and he counsels families that staggered regression

at later ages, while uncommon, does occur.

On commercial uptake, Dr. Lieberman expects a measured ramp

spearheaded by recently diagnosed, younger patients

He estimated that roughly 10% of his clinic per year electing gene therapy would represent

a meaningful uptake rate. The earliest adopters are likely to be families with the youngest,

most recently diagnosed children, who have the longest expected lifetime burden ahead.

Families of older patients (children in their 30s or 40s) are more likely to "sit back, watch

and see," both because they have adapted to the status quo and because of concerns