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Cobi has rhabdomyolysis and liver toxicity as warnings on the label, and ALT elevations can be due to either or both toxicities. Recent evidence suggests that certain neuromuscular diseases (SMA and ALS) also have myocyte dysfunction as primary and secondary drivers of pathophysiology.
SABER approached Cobi Safety Strategy Leader, approached NMD (SMA and ALS) BD reps, and PSTC SkM working group to engage in POC.
Skeletal muscle scientific sub-team provided skeletal muscle and GLDH biomarker strategy for cobi team to enable precision medicine and for NMD teams to complement neuro biomarker strategy.
Strategy: Tailored safety biomarker strategy based on known biomarker biology, non-published data from FDA, and comprehensive clinical trial review publication.
Assay: Virtual lab and PSTC working to develop skeletal muscle biomarkers as Roche Dx RPA; Pfizer and Merck resourced the assays for the POC
Operations: Supported clinical biomarker operations to smoothly integrate and operationalize the strategy into the protocol
Data Solution: Biostats provided for data analysis and visualization; Virtual lab working to transfer internal and PSTC skeletal muscle biomarker data into QUASAR
Safety monitoring of cobimetinib can be more precision by using GLDH and skeletal troponin I. Prospective analysis may enable predictive approach to patients predisposed to rhabdomyolysis.
Diagnosis and progression of spinal muscle atrophy is improved over standard assessments by using skeletal muscle biomarkers (especially skeletal troponin I, CkM and myostatin). Understanding source of ALT elevations is more precise by also using GLDH.
ALS patient populations are heterogeneous in their skeletal muscle biomarker profile and require larger data sets to understand potential utility. Understanding source of ALT elevations is more precise by also using GLDH.
Data sets will support PSTC skeletal muscle biomarker regulatory qualification
Know your biomarker biology relative to the pathophysiology of drug toxicity and disease.
Organ-based biomarkers can be used as safety, diagnostic, prognostic, and PD biomarkers if grounded in shared pathophysiology.
Reference data in disease indications is critical for accurate interpretation.
Consortia are an excellent means to generate POC data while conserving resources and leveraging expertise.
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