Phase III VALOR study data for BIIB 067 shows earlier initiation benefit in amyotrophic lateral sclerosis.- Biogen

The data show that earlier initiation of tofersen compared to delayed initiation (six months later in the open-label extension [OLE] study) slowed declines in clinical function, respiratory function, muscle strength, and quality of life. At the time of the analysis, because the majority of participants survived without permanent ventilation (PV), the median time to death or PV could not be estimated. However, early survival data suggest a lower risk of death or PV with earlier initiation of tofersen. These results are based on new integrated data from the pivotal Phase III VALOR study and its OLE study.

As previously reported in October 2021, VALOR, a six-month Phase III randomized study, did not meet the primary endpoint of change from baseline to week 28 in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). However, trends of reduced disease progression across multiple secondary and exploratory endpoints were observed. The new 12-month data further build on the results previously observed in the initial readout. The 12-month data compare early initiation of tofersen (at the start of VALOR) to delayed initiation of tofersen (six months later, in the OLE). Over 12 months in the overall study population, results favored earlier start tofersen on measures of: Clinical function as measured by ALSFRS-R (difference of 3.5 points; 95% confidence interval [CI]: 0.4, 6.7). Respiratory function as measured by slow vital capacity (difference of 9.2 percent-predicted; 95% CI: 1.7, 16.6). Muscle strength as measured by the handheld dynamometry megascore (difference of 0.28; 95% CI: 0.05, 0.52). Quality of life as measured by the 5-item amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-5) (difference of 10.3 points; 95% CI: -17.3, -3.2).

At the time of the analysis, because the majority of participants survived without PV, the median time to death or PV and median time to death, could not be estimated. However, early survival data suggest a lower risk of death or PV (Hazard ratio [HR] 0.36; 95% CI: 0.137, 0.941) and death (HR 0.27; 95% CI: 0.084, 0.890) with earlier initiation of tofersen. The latest 12-month biomarker results show that reductions in total SOD1 protein (a marker of target engagement) and neurofilament (a marker of axonal injury and neurodegeneration) were sustained over time. The data were presented at the European Network to Cure ALS (ENCALS) meeting in Edinburgh.