Researchers at Washington University in St. Louis tested tofersen, a drug injected into the spinal fluid to reduce production of the faulty protein directly, in patients with this inherited form of the disease, measuring both a blood marker of nerve damage and clinical function over 28 weeks.
Tofersen cut a key blood marker of nerve damage, neurofilament light chain, by about 60 percent in faster-progressing patients, while that marker rose in the placebo group. The trial's main clinical measure of disability did not show a statistically significant difference over the 28-week study period itself.
Despite missing its primary clinical goal, longer open-label follow-up suggested patients who started tofersen earlier declined more slowly than those who began later, and the strength of the biomarker effect was enough for the FDA to approve tofersen in 2023 partly on that marker rather than waiting for a longer trial to prove a clinical benefit outright, an unusual path for an ALS drug.
Read the original study
A drug judged partly on what it silenced.
Source
- Miller, T. M., Cudkowicz, M. E., Genge, A., Shaw, P. J., Sobue, G., Bucelli, R. C., Chiò, A., Van Damme, P., Ludolph, A. C., Glass, J. D., Andrews, J. A., Babu, S., Benatar, M., McDermott, C. J., Cochrane, T., Chary, S., Chew, S., Zhu, H., Wu, F., . . . VALOR and OLE Working Group (2022). Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. New England Journal of Medicine, 387(12), 1099–1110. https://doi.org/10.1056/NEJMoa2204705