Contributions
Abstract: EP1571
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Serum neurofilament (Nf) is a marker of axonal damage that correlates with MS disease activity and is modulated by anti-inflammatory MS therapeutics; however, the application of Nf in emerging remyelination therapeutics is not established. Opicinumab blocks LINGO-1, a negative regulator of myelination and axonal regeneration, and recent results from the SYNERGY study (NCT01864148) revealed an increased percentage of clinical improvement responders in the 10 mg/kg and 30 mg/kg cohorts. Post-hoc analyses further identified a subgroup that showed a greater and sustained clinical effect.
Objectives: To evaluate serum Nf light and heavy chain (NfL and NfH) levels in the 10mg/kg and placebo cohorts from SYNERGY to determine their potential utility as biomarkers of remyelination and patient stratification for opicinumab treatment effect.
Methods: High-sensitivity technologies were used to measure serum NfL (Simoa) and NfH (Ella) at baseline, week 36 and week 72 of the 10 mg/kg opicinumab and placebo cohorts. The following analyses were performed: (i) association of Nf with demographics, baseline and post-treatment imaging and clinical outcomes, including progression and improvement response; (ii) characterization of treatment-related effects on Nf and (iii) evaluation of Nf levels to stratify treatment responders from non-responders.
Results: Exploratory analyses indicated that baseline NfL and NfH levels are weakly correlated with age, baseline imaging parameters and selected clinical measures and seem to be influenced by prior MS treatment as levels are modestly higher in the treatment naïve individuals. NfL appears to be modestly associated with disease progression and improvement response, as NfL is slightly higher in progressors and non-responders at all time points. Furthermore, a trend of seemingly greater treatment-related NfL decline was observed in non-progressors and improvement responders. Interestingly, baseline NfH is not associated with clinical outcome and no treatment-related change in NfH levels was observed
Conclusions: Preliminary findings demonstrated that serum NfL, but not NfH, levels were associated with improvement responders and non-progressors and warrants further investigation of serum NfL as a potential biomarker of interest to assess remyelination. It will be critical to further understand the synergistic and relative impact of concomitant immunomodulatory agents and novel remyelination therapeutics on NfL.
Disclosure: Supported by: Biogen
Ankur Sharma: employee of Biogen and holds stock/stock options in Biogen
Wenting Cheng: employee of Biogen and holds stock/stock options in Biogen
Shifang Liu: employee of Biogen and holds stock/stock options in Biogen
Ih Chang: employee of Biogen and holds stock/stock options in Biogen
Bing Zhu: employee of Biogen and holds stock/stock options in Biogen
Sarah Sheikh: employee of Biogen and holds stock/stock options in Biogen
Devangi Mehta: employee of Biogen and holds stock/stock options in Biogen
Abstract: EP1571
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Serum neurofilament (Nf) is a marker of axonal damage that correlates with MS disease activity and is modulated by anti-inflammatory MS therapeutics; however, the application of Nf in emerging remyelination therapeutics is not established. Opicinumab blocks LINGO-1, a negative regulator of myelination and axonal regeneration, and recent results from the SYNERGY study (NCT01864148) revealed an increased percentage of clinical improvement responders in the 10 mg/kg and 30 mg/kg cohorts. Post-hoc analyses further identified a subgroup that showed a greater and sustained clinical effect.
Objectives: To evaluate serum Nf light and heavy chain (NfL and NfH) levels in the 10mg/kg and placebo cohorts from SYNERGY to determine their potential utility as biomarkers of remyelination and patient stratification for opicinumab treatment effect.
Methods: High-sensitivity technologies were used to measure serum NfL (Simoa) and NfH (Ella) at baseline, week 36 and week 72 of the 10 mg/kg opicinumab and placebo cohorts. The following analyses were performed: (i) association of Nf with demographics, baseline and post-treatment imaging and clinical outcomes, including progression and improvement response; (ii) characterization of treatment-related effects on Nf and (iii) evaluation of Nf levels to stratify treatment responders from non-responders.
Results: Exploratory analyses indicated that baseline NfL and NfH levels are weakly correlated with age, baseline imaging parameters and selected clinical measures and seem to be influenced by prior MS treatment as levels are modestly higher in the treatment naïve individuals. NfL appears to be modestly associated with disease progression and improvement response, as NfL is slightly higher in progressors and non-responders at all time points. Furthermore, a trend of seemingly greater treatment-related NfL decline was observed in non-progressors and improvement responders. Interestingly, baseline NfH is not associated with clinical outcome and no treatment-related change in NfH levels was observed
Conclusions: Preliminary findings demonstrated that serum NfL, but not NfH, levels were associated with improvement responders and non-progressors and warrants further investigation of serum NfL as a potential biomarker of interest to assess remyelination. It will be critical to further understand the synergistic and relative impact of concomitant immunomodulatory agents and novel remyelination therapeutics on NfL.
Disclosure: Supported by: Biogen
Ankur Sharma: employee of Biogen and holds stock/stock options in Biogen
Wenting Cheng: employee of Biogen and holds stock/stock options in Biogen
Shifang Liu: employee of Biogen and holds stock/stock options in Biogen
Ih Chang: employee of Biogen and holds stock/stock options in Biogen
Bing Zhu: employee of Biogen and holds stock/stock options in Biogen
Sarah Sheikh: employee of Biogen and holds stock/stock options in Biogen
Devangi Mehta: employee of Biogen and holds stock/stock options in Biogen