Castle Biosciences Eyes Growing Precision Dermatology Market for New Test

Original from: genomeweb

As part of its strategic expansion into precision dermatology, Castle Biosciences recently introduced a new assay to guide systemic treatment decision making for the immune-driven disease atopic dermatitis. Castle expects to expand the limited launch of its AdvanceAD-Tx test over the next year to pursue a total addressable market that it estimates to be as much as $33 billion.

Castle's founders intended to target niche but potentially profitable diagnostic spaces from the outset when the company launched in 2008, Derek Maetzold, cofounder and CEO of the Houston-based company said. The company's estimate for the total addressable market for the AdvanceAD-Tx test is based on an approximate 13 million people 12 years of age and older with moderate to severe atopic dermatitis, full market penetration, and "a reasonable reimbursement rate" for the test, Maetzold said. This potential market would be about 60 times larger than that for its DecisionDx melanoma test.

"It's really a fantastic opportunity," Maetzold said in a recent interview.

The large TAM reflects a large unmet need for personalized treatments in dermatology but also figuratively mirrors the behemoth gene expression panel - AdvanceAD-Tx assesses a total of 487 genes from a skin scraping sample to give clinicians clues about the status of 12 immune pathways.

Chronic itch remains somewhat of a neurobiological mystery, and the itch of certain skin conditions has been known to drive people to desperate measures. Severe atopic dermatitis, in particular, causes intense, sometimes unbearable itching along with physical and psychosocial stress from flares of red, flaky skin patches and oozing or weeping blisters. Adults are most often afflicted in skin creases of the elbows, knees, hands, and eyelids.

Considered an immune system overreaction and a type of eczema, milder forms of atopic dermatitis are sometimes treatable by topical ointments. Systemic medications, first approved by the US Food and Drug Administration in 2017, offer new options for moderate and severe cases. These include interleukin-blocking biologics targeting the Th2 inflammatory pathway - like Sanofi and Regeneron's Dupixent (dupilumab), LEO Pharma's Adbry, (tralokinumab), Eli Lilly's Ebglyss (lebrikizumab), and Galderma Laboratories' Nemluvio (nemolizumab) — as well as small-molecule JAK inhibitors targeting multiple inflammatory pathways, such as Pfizer's Cibingo (abrocitinib), Lilly's Olumiant (baricitinib), and AbbVie's Rinvog (upadacitinib).

These new therapies are costly and can have side effects, according to one recent review, so they are typically reserved for more severe cases. And, unfortunately, patients who start on systemic treatment sometimes only see temporary improvement followed by recurring flares, while others never achieve sustained control at all. The frequent switching between systemic treatments highlights the need for precision medicine approaches, according to another recent study.

The Castle team used machine learning-based classification to develop its panel and found it could reliably distinguish an immune signature that would likely best respond to JAK versus Th2-targeted systemic treatments.

The firm then initiated a multiyear prospective study of the test at 49 US sites beginning in 2021. Called the Inflammatory Skin Disease Treatment Identification Study, or IDENTITY, the study found that for the approximately 30 percent of patients with a JAK inhibitor responder profile, treatment with a JAK inhibitor led to higher rates of disease reduction by three months and quicker response than that seen in patients with the JAK responder profile who were treated with a Th2-targeted therapy.

Maetzold said the firm is now pursuing multiple pathways to accelerate patient access to AdvanceAD-Tx, including potentially partnering with pharmaceutical companies. Meantime, the firm is phasing in sales to dermatologists who have already adopted its melanoma testing services.

"The vast majority of these dermatologists are doing skin cancer work and atopic dermatitis work, so it's our same customer base," Maetzold added. The feedback so far has been wonderful, he said, since clinicians see a need to quickly get suffering patients onto an effective therapy.

Precision dermatology

Aaron Farberg, a Dallas-based dermatologist and an adviser for Castle, said the AdvanceAD-Tx test offers an advantage over the standard of care for AD, which includes subjective clinical measures and patient-reported symptoms and treatment history. Patch testing can only detect suspected contact dermatitis, while bloodwork and biopsies are often nonspecific and unhelpful. "None of these tools provide molecular insight into which therapeutic class is biologically appropriate," Farberg noted.

Although the test is likely to be most useful for patients beginning systemic therapy or switching due to inadequate response — a group which includes almost all moderate to severe cases except those that are stable on their current therapy — in Farberg's opinion the information provided by the AdvanceAD-Tx test "is powerful and should be available to all AD patients."

The noninvasive nature of the Castle test is also compelling, he suggested. And, to his mind, "it will reduce therapeutic cycling [because] instead of guessing which pathway is dominant, the test identifies the most active immune pathways in each patient."

The multicenter clinical validation also lends credibility to the test, since study data showed patients with a JAK inhibitor responder profile "do markedly better on a JAK inhibitor than on a biologic," he said, achieving nearly four times faster overall skin clearance, higher rates of non-itching, as well a higher likelihood of being flare-free. "The objective biology provided by the AdvanceAD-Tx test increases confidence in initial systemic therapy choice for patients with AD," Farberg said.

In addition to Castle Bio's test, Mindera Health's sequencing-based RNA biomarker psoriasis response test, Mind.Px, demonstrated clinical utility earlier this year, "showing that Mind.Px testing changes physician prescribing behavior and produces better outcomes for psoriasis patients, at least in the short term." Farberg coauthored a paper last year comparing published research on the Mindera and Castle tests, suggesting that the technologies may someday help reduce the significant morbidity of uncontrolled inflammatory skin disease.

Farberg hopes wider availability and integration of the test into everyday dermatology workflows will soon improve patient care. "As this is a new test, integration will take time, although I expect adoption of the test will be relatively quick," he said, adding that continued real-world outcome data Will need to be gathered as more clinicians utilize the test.

Maetzold, meanwhile, said the ultimate goal for Castle now is to enable more clinicians "to make the best choice the first time for patients who have been suffering disease, in many cases, for many years."

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