Leveraging Biology for Better Informed Treatment Decisions
Dec 12th, 2022 , Ferhan Qureshi
Nearly five years ago, I was the first employee to be hired after our co-founders established Octave Bioscience. In my role as Vice President, Biomarker Product Development, I was responsible for building the team that drove the development, validation and launch of our blood-based biomarker test for multiple sclerosis disease activity (MSDA), taking our MSDA test from concept to reality in these few short years. Our activities have ranged from R&D, setting up a CLIA/CAP accredited laboratory, working closely with our data science team, analytical & clinical validation to continued development activities as we move our pipeline forward.
The need for an objective measure of MS disease activity was established before the founding of Octave. Previously some work had been done in the area of proteomics; however, those options were fairly invasive, requiring patients to undergo spinal tap for CSF analysis or were heavily focused on a single biomarker approach. We felt there was a better way, and one of our guiding concepts from the beginning was that our test had to be minimally invasive and convenient for patients and physicians. Our MSDA test is a routine blood draw, similar to what a patient with any condition might undergo for any common laboratory test. Furthermore it was essential that any blood test we developed reflected the complexity and heterogeneity of the disease and therefore was expected to leverage a multi-biomarker approach.
Over the last decade or so, technology around blood-based serum proteomics has advanced rapidly, and many of our lab team had prior experience with successful proteomics products for a range of health conditions. Leveraging these powerful technologies and our team’s extensive experience, we began our work by assessing more than 1400 blood-based proteins in patients with MS. Through our development and validation processes, we culled that large group of proteins to a smaller panel of proteins highly significant for MS disease activity.
MS is complex and heterogeneous. There are multiple pathways, cell types and mechanisms involved with the disease. Our initial hypothesis, born out in our validation studies, was that we needed to holistically account for the multiple factors at play, rather than focusing on a single protein. The 18 proteins ultimately included in our MSDA are associated with four pathways in the areas of immunomodulation, neuroinflammation, myelin biology and neuroaxonal integrity.
We developed an algorithm to determine a patient’s overall disease activity score by incorporating scores for each of these pathways as well as for individual proteins. When patients receive their overall disease activity score, it is categorized as low, moderate or high. These categories were created based on how our MSDA test scores correlated with radiographic and clinical indications of disease activity during our validation studies.
The MSDA score provides neurologists and their patients an objective, quantifiable metric as they assess the efficacy of new and current therapy options and work toward a goal of no evidence of disease activity, or NEDA. Additionally, our test offers insights into activity not yet discernible through clinical and radiographic assessments. While factors including safety profiles, routes of administration, payer coverage, patient preference and side effects will continue to affect therapeutic selection, the MSDA score offers an additional, objective input to augment the available clinical and radiographic information.
In keeping with our guiding concept, we’ve made the test as simple and convenient as possible to administer. In addition to a simple blood draw, providers complete a requisition form capturing basic information, such as age, gender, current therapy, years since diagnosis and reason for testing, that is accounted for in our score assessment or helpful in contextualizing the patient’s result. Once the blood sample is shipped to our lab, we run the assay and do extensive quality control on the results before releasing a report back to the neurologist. In addition to offering disease pathway scores and an overall disease activity score and categorization, the two-page report includes the 18 individual biomarker concentrations along with the percentiles relative to other MS patients..
In clinical practice, providers currently are using our MSDA test to help determine if a therapy is efficacious, utilizing the affirmative signals that can appear within a three- to six-month range, compared to the 12- to 18-month wait for a negative signal that is often required in the current standard of care. Our test is also being used for routine monitoring to distinguish whether symptoms a patient may be experiencing are related to MS activity or other factors. Because MS affects each patient so uniquely, it can be hard to determine whether a symptom is related to MS without an objective measure. We are confident that the utility of our test will continue to expand along with the body of evidence supporting additional use cases.
A number of our studies are available at this link. We recently returned from ECTRIMS, an international scientific meeting, at which we presented data further validating our test’s algorithm in other studies and real-world applications. We also showed expanded use of the assay panel and shared progress on our development of a pipeline product to assess disease progression. We are fortunate to work in collaboration with leading researchers and institutions around the world to make these objective, quantitative options available to patients.
At Octave, we are proud to be part of advancing the science for MS and helping to equip neurologists and their patients with quantitative, objective measurements for more informed decision-making. As our MSDA test becomes more deeply integrated with our Clinical Insights and MRI Insights programs through our MS Precision Care Solution, we believe that we are on the forefront of changing the paradigm and creating a new standard of MS care where patients with MS can live more harmonious lives.