Biogen Announces Topline Results from the Tofersen Phase 3 Study and its Open-Label Extension in SOD1-ALS - Seite 3

The open-label extension study is an ongoing Phase 3 study for participants who completed VALOR. Of the 108 participants in VALOR, 95 enrolled in the OLE.

Topline Results

In VALOR the primary efficacy endpoint of change from baseline to week 28 in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score in the primary analysis (faster-progressing) population did not reach statistical significance as measured by a joint-rank analysis (difference of 1.2; p=0.97).   

Trends favoring tofersen were seen across multiple secondary and exploratory measures of biologic activity and clinical function, including motor function, respiratory function, and quality of life. On the first key secondary endpoint of change from baseline in total CSF SOD1 protein, a marker of target engagement, differences were observed between the tofersen and placebo groups of 38% and 26% in the faster- and slower-progressing populations, respectively. On the second key secondary endpoint of change from baseline in plasma neurofilament light chain (NfL), a potential marker of neuronal degeneration, differences were observed between the tofersen and placebo groups of 67% and 48% in the faster- and slower-progressing populations, respectively.  

In the faster-progressing population, trends favored tofersen on measures of respiratory function (Slow Vital Capacity (SVC); difference of 7.9 percent-predicted) and muscle strength (Hand-held dynamometer (HHD); difference of 0.02). Similar trends were observed across multiple exploratory patient-reported outcome measures of disease severity, quality of life, and fatigue. Median time to event could not be estimated for survival analyses due to the low number of events over the 28-week period.

In addition, with longer-term follow up in the OLE, earlier tofersen initiation consistently led to a reduction in decline in measures of clinical function across the population.

The most common adverse events (AEs) in participants receiving tofersen in the VALOR study were procedural pain, headache, pain in extremity, fall and back pain. Most AEs in both VALOR and the OLE were mild to moderate in severity. In VALOR, serious AEs were reported in 18.1% of participants receiving tofersen and 13.9% of those receiving placebo. In the tofersen group, 5.6% of participants discontinued treatment due to an AE. There were no discontinuations due to AEs in the placebo group. Serious neurologic events were reported in 4.8% of patients receiving tofersen in VALOR and its OLE, including 2 cases of myelitis (2.0%). There was one death reported in the tofersen-treated group in VALOR, which was determined not to be related to tofersen.