NEW YORK – Mindera Health is betting its test to analyze mRNA transcripts will save time for physicians and patients struggling to find the right psoriasis treatment, though some skin doctors would like to see more clinical validity and utility data.
Psoriasis is a chronic autoimmune condition that causes scaly patches on the skin, known as plaques. Patients can try various treatments to manage their symptoms, including topical corticosteroids, light therapy, and retinoids. In particular, the use of biologics that target and suppress specific parts of the immune system have been rapidly rising since they first entered the US market in 2003. These biologics are typically prescribed to patients who have a moderate-to-severe form of the disease and have already failed other kinds of therapies.
Still, it can take time to identify an appropriate biologic treatment, and patients may need to try multiple options before finding one that's effective for them.
"That disconnect between the very high cost but [the lower-than-expected] response stood out to us," said Toby Dickerson, cofounder and CSO of Mindera, a firm that has developed an mRNA-based laboratory test that can personalize biologics prescribing, dubbed Mind.Px. "What if you could predict which drug would work for a patient earlier?" Dickerson said, describing the rationale behind the test.
In fact, 82 percent of dermatologists say they end up switching biologics for 10 percent to 30 percent of patients within the first year of treatment, according to a 2021 survey funded by Mindera and published in Dermatology and Therapy. In addition to the frustration of trial-and-error prescribing, this can also be a financial burden for patients, since these biologics are expensive and not always covered by insurance. Biologics for plaque psoriasis, the most common type of psoriasis, can rack up annual costs in the range of $1,664 to $79, 277, according to a study published in JAMA Dermatology.
Mindera started selling its transcriptomics test, Mind.Px, commercially in the US in 2022, almost a decade after launching the company in late 2013. Mind.Px must be ordered and performed by a clinician such as a dermatologist or rheumatologist. Healthcare providers may be able to submit for insurance coverage using a CPT code, Dickerson said. The list price for the test is $4,800.
The test is designed to predict which class of biologic a patient is likely to respond to, based on an analysis of mRNA from a biological sample obtained via a minimally invasive, penny-sized patch placed on the skin for five minutes.
These samples are sent for sequencing to Mindera's lab in San Diego, which is accredited by the College of American Pathologists and CLIA-certified. Mind.Px gauges about 100 mRNA biomarkers that the company has determined are predictive of drug responses, building on research conducted by Dickerson and Tahir Mahmood, Mindera's other cofounder and board member, at the Scripps Research Institute in La Jolla, California. To home in on the predictive mRNA biomarker set, researchers at Mindera sifted through existing retrospective research and trained a machine-learning algorithm on a dataset of molecular and clinical information from psoriasis patients.
The medication recommendations from Mind.Px are compiled into a report that details whether a patient is likely to be a responder or non-responder to three classes of biologics: TNF-alpha inhibitors, IL-17 inhibitors, and IL-23 inhibitors. The average turnaround time from sample collection to doctors receiving the report is 10 days but can take up to 14 days, Dickerson said. The reports are delivered to physicians through a secure email, an eFax, or an integration with Modernizing Medicine's EMA, an electronic health record system that's designed for dermatology practices. Mindera is working on integrations with other electronic health record systems.
Dickerson expects that the test results will not only lead to less trial-and-error prescribing and allow patients to receive treatments they're responsive to earlier but may also result in fewer wasted doses of an expensive medication.
"We're fortunate that we have good treatment options [for psoriasis]," said Joel Gelfand, a professor of dermatology and director of the University of Pennsylvania's Center for Clinical Sciences in Dermatology. "Oftentimes, just by using your best guess, a patient should do pretty well." But he acknowledged that despite the variety of good treatment options, patients' responses can differ, for example, in terms of how much joint pain and stiffness relief they experience on a particular drug.
When deciding which medications to prescribe psoriasis patients, Gelfand said he reviews their medical and prior treatment history and discusses their preferences. Having more information from a test like Mind.Px could be helpful in guiding those decisions, he said, but Gelfand would like to see data from large, prospective studies evaluating the usefulness of this type of mRNA-guided approach. He'd like to see evidence of whether or not patients' long-term clinical outcomes are significantly better when treatment is informed by testing versus without testing.
Mindera advertises that its test has a more than 91 percent positive predictive value (PPV). In a 2021 study testing the company's predictive algorithm on psoriasis patients, investigators reported PPVs for the three drug classes ranging between 85.7 percent and 93.1 percent in SKIN: The Journal of Cutaneous Medicine. The PPVs were even higher when homing in on patients with severe psoriasis, pushing the values in the range of 90 percent to 100 percent.
There's been significant interest in the concept of biomarker-guided prescribing among skin doctors. In the most recent joint guidelines from the American Academy of Dermatology and the National Psoriasis Foundation, released in 2019, a multidisciplinary work group said additional research is needed to develop biomarkers that predict appropriate biologic agents for individual patients.
It's always helpful to have more information to guide decision-making, said Lawrence Green, a clinical professor of dermatology at George Washington School of Medicine and Health Sciences and a former member of the board of directors of the American Academy of Dermatology. That doesn't mean physicians should automatically follow recommendations from a test, though.
"Every piece of information we have that will inform us about what will work best for a patient is helpful," Green said. "That doesn't mean it has to be used." Ultimately, Green stressed that care decisions should be made through shared decision-making with the patient after considering a range of factors, including patient preferences and lifestyle.
That was a key focus of the 2019 guidelines, in which the authors emphasized that patients should be educated about the safety and efficacy of different treatment options, their cost, dosing schedules and regimens, and other factors that may affect their quality of life.
There are many considerations to weigh when it comes to choosing the right treatment for psoriasis patients, said Paras Pankaj Vakharia, an assistant professor of dermatology at Northwestern University's Feinberg School of Medicine. If a patient is averse to injections, for example, it might be worth seeing if there's a treatment combination that could work without biologics or a treatment regimen where a biologic is injected infrequently. Moreover, the drug deemed most likely to work for a patient by a test may be out of reach due to lack of insurance coverage or payor requirements that the patient try lower-cost therapies before an insurer will pay for a more expensive one.
A biomarker test that predicts medication response would certainly be helpful for informing which medications to try first, Vakharia noted, but he also wanted more evidence and validation before trying a test like Mind.Px for guiding patients' treatments. He cautioned that in the 2021 paper, researchers had reported high PPVs with Mindera's test, but that negative predictive values (NPV) were 28.6 percent for IL-23 inhibitors and 22.2 percent for IL-17 inhibitors — which leaves room for false negatives, where the test may give patients a low shot of responding to a medication when they actually might. In patients with severe psoriasis, NPVs were 33.3 percent for both of those drug classes.
Mindera Health has focused its development efforts on optimizing PPV after consulting with doctors, Dickerson said.
"After many discussions with psoriasis experts in our development phase and hearing their recommendations based upon their extensive experience with the biologics, the question they asked most often is which biologic class will work the best for the patient," he said. "For that reason, Mind.Px has been optimized for positive predictive value to answer that specific question."
While some skin doctors are being cautious in embracing a relatively new test like Mind.Px, Mindera claims to have sold hundreds of tests since its commercial launch two years ago. In February, Mindera partnered with pharmacy benefit manager Liviniti, allowing employers to offer the Mind.Px test to employees in the hopes of getting them on appropriate psoriasis medications more quickly. Mindera also has signed agreements with MediNcrease Health Plans and Contigo Health's ConfigureNet to make Mind.Px available to patients within their networks.
While Mindera is focused on driving adoption of Mind.Px in psoriasis this year, that's just the beginning, Dickerson said. Looking ahead, Mindera wants to expand the test platform to other inflammatory skin conditions, such as atopic dermatitis, and explore whether biomarkers from the skin can be used to inform prescribing in other specialties, such as for gastrointestinal or cardiovascular diseases.
There may be further opportunities in harnessing the mRNA biomarker analysis performed by Mind.Px to diagnose diseases that provide an alternative to blood- or tissue-based tests, too. "We're thinking about using the skin as a window into human health as a whole," Dickerson said.