Researchers at Scipher Medicine have combined proprietary data and artificial intelligence to predict a patient’s response to costly biologics. Slava Akmaev, Ph.D., Scipher Chief Technology Officer and Head of Therapeutics describes the implications of their new study, Network-004 that demonstrates the ability of PrismRA® to identify anti-tumor necrosis factor inhibitor (TNFi) therapy non-responders in both naïve and TNFi exposed patient populations.
PrismRA is a molecular test that leverages proprietary data to detect inadequate responders to tumor necrosis factor inhibitor (TNFi) therapy in moderate or high disease rheumatoid arthritis (RA). This is important because the anti-TNFs are the most commonly prescribed first line targeted therapy in RA. The test was built around detecting potential non-response in these patients initiating their first biologic.
Our latest publication, Cohen et al., reveals that PrismRA can be used to test response to anti-TNFs not only in treatment naïve patients, but also TNFi-exposed patients. The study focused on patients who failed their conventional sDMARD therapy and were considering getting on the anti-TNF drugs, or small molecule targeted therapy, such as JAK inhibitors. We validated PrismRA in four patient cohorts including a clinical observational study performed in multiple sites across the United States.
Imagine a patient who started a TNFi a few months ago and who may now be at the point where they’re trying to evaluate and make the decision whether to continue their current anti-TNF course or switch to a different therapy. This is where the PrismRA is extremely useful. Patients can take the test and understand if the anti-TNFs are likely to improve their disease state. PrismRA can help to guide that decision by calculating a score to indicate whether the patient is unlikely to respond to the treatment in a meaningful way. We found in our Network-004 research that the test has statistical power to predict their six months outcomes.
RA patients become refractory to their treatments after a certain period of time. This could happen because they develop antibodies to the drug or because their cell molecular make-up changes. PrismRA makes it possible to look at the molecular profile and understand where the patient is as it relates to their response to treatment.
In theory, clinical use of PrismRA can increase response rates to targeted therapies by 40% by the ACR50 metric. That translates to 12 additional patients achieving ACR50 response in 6 months out of a 100. We are in the middle of conducting a number of clinical utility and RWE studies that will look into it in more detail.
Achieving remission with a first-line treatment may potentially allow patients to manage the disease better and maintain their current lifestyle, unfortunately, there is no cure for RA at present. We know if the first targeted therapy is not correctly selected, patients will experience disease progression and experience molecular shift such that, even when they get on the right therapy, the response rates may be lower. Moreover, the analysis that we’ve performed on published data comparing first-line therapy response to response to second-line or third-line therapy indicates that the patient response to the correct first-line therapy is greatly enhanced. We thus believe that patients who can make that switch earlier will have a completely different disease trajectory.
That’s a great question because, interestingly enough, while precision medicine in oncology is commonplace, it is new in rheumatology. As evidence of this, the just-released American College of Rheumatology (ACR) guidelines had precision medicine out of scope.
PrismRA is the first predictive test in rheumatoid arthritis. We are developing this market and educating rheumatologists and the community about use of precision medicine in clinical practice. Scipher is trailblazing this space and we expect to see more attention paid to predictive diagnostics in RA in the years to come.
As has happened with oncology, I think a focus on precision medicine may change the way we think of rheumatic diseases. I think in the case of rheumatoid arthritis and other autoimmune diseases, such as inflammatory bowel disease and psoriatic arthritis, there’s probably a number of patient groups that share molecular mechanisms that drive disease. As with oncology, we will begin in rheumatology to look at molecular mechanics and molecular dysregulation to identify phenotypes of patients more likely to respond to certain therapeutic interventions.