Biomarker diagnostic tests in precision medicine can stratify patient sub-populations into ... [+]
Precision medicine’s promise is selecting the right drug for the appropriate person in a timely manner. But besides cancer, in most disease areas trial-and-error prescribing of therapeutics continues to reign, even when tests are available to differentiate between responders and non-responders and those who are susceptible or not to adverse events. This can lead to substantial waste of healthcare resources. Science still outpaces commercialization of many diagnostic tests. Changes to the reimbursement model to align price with value could offer a remedy.
Genomic tests which detect the presence of certain biomarkers can personalize therapy selection, diagnose specific disease types and predict level of response. A diagnostic is said to have clinical utility if the test leads to changes in the medical management of a patient population and improves health outcomes.
For example, breast cancer patients taking Herceptin (trastuzumab) must be HER2-positive in order for the drug to be effective. This means that prior to being prescribed Herceptin they undergo diagnostic testing to find out if cancer cells have a high level of the human epidermal growth factor receptor 2.
Non-small cell lung cancer can also be differentially treated with therapies targeted at tumors with specific biomarkers, including epidermal growth factor receptor, anaplastic lymphoma kinase and others.
So-called companion diagnostics are widely used in cancer. They often appear on the Food and Drug Administration-approved label as a prerequisite to prescribing certain therapeutics.
Alzheimer’s Disease
Besides cancer, there are other diseases which have underlying biomarkers that can distinguish between patients in terms of their level of responsiveness to medicines and degree of experiencing adverse events. Most patients with Alzheimer’s Disease, for example, have accumulation of beta amyloid plaque in their brains. New drugs like Leqembi (lecanemab) clear such plaque in early-stage AD patients. But to avoid the risk of no benefit and dangerous side-effects it’s imperative that a correct diagnosis of plaque build-up is given prior to prescribing Leqembi. For this, brain scans must be performed. After Leqembi’s FDA approval last year, Medicare finally decided to routinely pay for imaging tests such as Amyvid (florbetapir F 18)—which had been on the market since 2013 but largely unreimbursed—to detect beta amyloid plaque in Alzheimer’s disease patients.
Furthermore, approximately 20% of patients who are infused with lecanemab develop brain changes called amyloid-related imaging abnormalities or ARIA, which involves brain bleeding or swelling. People who carry a specific gene version called APOE-ε4 are more susceptible to developing ARIA and associated serious complications. And so it’s crucial that all patients must receive APOE gene testing before consideration of lecanemab use.
Auto-Immune Disorders
But except for cancer, AD and a handful of other diseases, tests to detect biomarkers aren’t deployed as much. To illustrate, an anti-tumor necrosis factor therapy such as Humira generally works for less than 50% of Crohn’s disease patients, according to studies cited by the sponsor. And although a better success rate is achieved for rheumatoid arthritis patients it is still less than 65%.
There are ways in which payers and patients could potentially save billions of dollars from applying the methods underlying precision medicine. In the case of the autoimmune disorder rheumatoid arthritis, diagnostics can first be used to tell in advance whether joint pains are driven by TNF. If levels are higher than normal, it suggests inflammation which can be treated. TNF-inhibitors are prescribed to an estimated 18 million rheumatoid arthritis patients globally but they’re not clinically effective at all for at least several million.
Further, blood-based identification of non-responders to anti-TNF therapy is crucial. Equipped with a blood test capable of predicting an individual’s response—or lack thereof—Scipher Medicine says it’s on a path to “cracking the code of rheumatoid arthritis treatments.” The company’s PrismRA test analyzes each patient’s molecular signature to determine whether they’ll respond positively to TNF-inhibitor therapy. The product employs a predictive model that combines clinical factors, blood tests and 19 gene patterns to identify patients who are “very unlikely” to respond to anti-TNF drugs.
However, PrismRA isn’t routinely covered by insurance, according to KFF, though a decision by the Centers for Medicare and Medicaid Services last October to begin reimbursing for the test may boost its use.
Mindera Health is another company involved in developing and manufacturing diagnostics for people with auto-immune disorders, in this case a dermal patch or skin analytic test to guide treatment of psoriatic patients.
The firm announced February 29 that it had formed a partnership with a non-traditional pharmacy benefit manager, Liviniti, to improve the management of moderate-to-severe psoriasis patients using a test called Mind.Px. The success rate in terms of patient responses to currently available biologics is roughly 52%. Mind.Px is a first of its kind diagnostic to steer prescribing decisions in psoriasis towards the most appropriate treatment. The program submits that it will boost clinical outcomes while reducing drug costs for self-insured employers.
According to a study published in Dermatology and Therapy, surveyed dermatologists said Mind.Px would “lessen trial and error” and provide an important a tool to “make more informed decisions about drug selection, improve patient outcomes, and significantly reduce wasted spending.”
To raise the profile of Mind.Px, Mindera Health initiated a coverage with evidence development project last year with the insurer Highmark and its health plan affiliates in Pennsylvania, West Virginia and Delaware. Here, Mind.Px’s coverage is conditioned on data gathering to demonstrate its effectiveness. This initiative evaluates trends in physician utilization, health outcomes, drug switching among psoriasis patients and overall net savings stemming from the test’s usage versus a control group.
NASH
Non-alcoholic steatohepatitis is fast becoming the most important etiology for advanced liver disease, according to an article in the British Medical Journal. The disease is associated with obesity, hypothyroidism, diabetes and high levels of fat in the blood. It causes excess build-up of fat in the liver and causes inflammation and scarring. A newly approved treatment, Rezdiffra (resmetirom), for NASH has no liver biopsy on the label, despite it being included as a requirement in the clinical trial upon which marketing authorization was based.
While biopsies may be the gold standard, they’re both invasive and often unnecessary. Nevertheless, other non-invasive tools such as the FibroScan can be used. FibroScan was licensed by the FDA as a diagnostic device to measure liver scarring or fibrosis caused by a number of liver diseases, including NASH. However, historically there’s been relatively poor reimbursement for FibroScan, both in terms of the percentage of plans that cover it, about two-thirds, and the rate at which it is covered. Notably, a study published in the American Journal of Gastroenterology found that all Medicaid claims were denied.
FibroScan is one of multiple biomarker tests that are essential to identify effective therapies, but also to rule out people unlikely to have advanced liver disease. Without adequate access to such tests, though—through Medicare, Medicaid or commercial insurance—iterative methods of prescribing pharmaceuticals will prevail. This in turn could lead to more wasteful spending.
Reimbursement Reform Needed
Science still outpaces commercialization of many diagnostic tests. When done effectively, precision medicine allows for more efficient deployment of costly medicines.
But to better accomplish this, the pricing and reimbursement model for diagnostic tests needs to be reformed, according to Lena Chaihorsky, who is co-founder and senior vice president of ALVA10. Reimbursement systems are outdated in that they’re administratively set to reflect the costs of producing and conducting tests—sometimes called a cost-plus determination—but not the value they confer. Correspondingly, Chaihorsky says this creates an environment where financial incentives are misaligned, as more treatments are used and paid for, whereas diagnostics—that could optimize treatment and make care more efficient from a clinical and economic perspective—are not prioritized. Their use isn’t sufficiently rewarded.
While attempts have been made since the early 2010s by public payers, including Medicare contractor Palmetto GBA’s MolDX program, to link diagnostic tests’ prices to their value, insurers still largely employ antiquated systems of reimbursement which don’t reflect the risk involved in developing a test or its value in the marketplace. Were this same model applied to pharmaceuticals, government and commercial insurers would set prices for drugs based upon the cost to manufacture and administer them. This isn’t appropriate for drugs or diagnostics. The path to greater adoption of precision medicine could be facilitated by a comprehensive reset of the pricing and reimbursement system for biomarker tests.
