Novartis has announced encouraging results from the Phase I/II FORTITUDE clinical trial of delpacibart braxlosiran (del-brax), an investigational treatment for FSHD. The study met its primary biomarker endpoint, marking an important step forward in the development of potential disease-modifying treatments for FSHD.
Del-brax is designed to target DUX4, a gene widely considered to drive the disease process in FSHD. Researchers found reductions in KHDC1L, a promising biomarker linked to DUX4 activity, as well as lower levels of creatine kinase (CK), a marker associated with muscle damage. These results suggest the treatment is affecting the underlying biology of the disease.
Why biomarkers matter in FSHD research
Biomarkers are measurable signs that help researchers understand whether a treatment is working as intended. While biomarker changes do not show directly whether a person is stronger or functioning better, they can provide important evidence that a therapy is affecting the disease process.
In the FORTITUDE study, lower KHDC1L levels suggest that del-brax reduces DUX4 activity, while lower CK levels may indicate less muscle damage. Together, these findings support the continued development of the therapy.
What is del-brax?
Del-brax is an investigational RNA therapy designed to address the root cause of FSHD by reducing abnormal DUX4 activity. The treatment has received Orphan Drug designation from both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and FDA Fast Track designation.
Results support ongoing Phase III trial
The FORTITUDE Phase I/II study evaluated the safety, dosing, and biological activity of del-brax. The biomarker cohort included 51 participants aged 16 to 70 years who received either del-brax or placebo over 12 months. The study successfully met both its primary and key secondary biomarker endpoints.
These findings support the global Phase III FORTITUDE-3 trial, which is currently enrolling around 200 people with FSHD. The study aims to determine whether the biological effects seen with del-brax translate into meaningful clinical benefits for patients.
What this means for the FSHD community
The results provide further evidence that targeting DUX4 may be a promising approach for treating FSHD. While the findings are encouraging, further clinical data will be needed to show whether these biological changes lead to meaningful improvements in daily life for people living with the condition.
FSHD Europe welcomes this continued progress in FSHD research and we thank the clinical trial participants, families, researchers and healthcare professionals whose contributions make advances like this possible.
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