AMPEL BioSolutions is recruiting individuals with systemic lupus erythematosus (SLE) into an observational study of its blood-based prognostic gene expression assay LuGene to demonstrate a correlation between test results and standard clinical evaluations.
In addition, the company has been conducting a study to see whether different lupus subtypes as defined by its test correlate with therapeutic response.
These studies follow another one published in October in the journal Genome Medicine that showed evidence for eight transcriptionally defined SLE endotypes, or subgroups, and demonstrated LuGENE’s ability to predict patients at risk for episodes of worsening symptoms called flares with high sensitivity and specificity.
“The biggest problem in lupus today is that there is no way to predict flares,” said Amrie Grammer, AMPEL’s Co-Founder, President, and CSO.
In addition, “patients are not only undergoing potentially life-threatening flares and hospitalization,” Grammer said, “but also side effects of drugs that never have the opportunity to work for them.”
SLE is an autoimmune disease in which the body’s immune system attacks healthy tissue of the skin, joints, kidneys, brain, and other organs. SLE patients currently have few therapeutic options and often receive medications off-label. The two medications approved specifically for SLE by the US Food and Drug Administration are Saphnelo (anifrolumab), sold by AstraZeneca, and Benlysta (belimumab), sold by GlaxoSmithKline. In addition to a range of side effects, not all patients respond well to these therapies.
In last year’s study, AMPEL researchers leveraged machine learning approaches and different gene expression platforms to identify the eight endotypes from 17 transcriptomic SLE datasets from 3,166 lupus patients of diverse genealogical backgrounds.
Individuals with the least perturbed transcriptional profiles showed the lowest disease activity while greater degrees of transcriptional perturbation correlated with more severe disease and higher likelihoods of experiencing flare-ups over the subsequent year.
From this data, AMPEL identified inflammatory and immunologic transcriptomic features from which it could calculate a prognostic clinical metric called the Lupus Cell and Immune Score (LuCIS), which the Charlottesville, Virginia-based company says could help estimate lupus activity not captured by other approaches.
The SLE subtypes identified in the study also showed ancestry-specific differences.
Although most subtypes were seen in all ancestries, their distributions within each ancestry group varied. Very few individuals of African ancestry, for example, were identified with subtypes that correlated with the least amount of immunologic perturbations, while few individuals of largely European ancestry were found in the subset with most perturbations.
Similarly, LuCIS scores showed therapy-based differences, suggesting that the assay could be used to predict drug response. The researchers also noted that therapy responsiveness correlated with greater likelihoods of experiencing symptom flare-ups.
Leah Kottyan, a professor of pediatrics at the Cincinnati Children’s Hospital Medical Center, whose research often focuses on lupus, said in an email that AMPEL’s study is “important,” noting that SLE is a very heterogeneous diseases wherein no two patients have exactly the same clinical experience.
“If a physician knew that a patient was likely to develop kidney disease, for example, they might have more regular screening for protein in the urine,” Kottyan said.
Kottyan also found it notable that AMPEL conducted its study by reusing data from prior studies, which it analyzed to expand our knowledge of lupus biology.
“When teams such as this one reuse data,” she said, “it maximizes what our scientific community can learn from samples provided by patients and experiments that were performed with public resources.”
Grammer said that the Genome Medicine study generated the data needed for CLIA validation of its assay, which it obtained last year.
AMPEL launched LuGENE in collaboration with California-based contract lab Research Dx. The AMPEL Genomic Platform technology, which uses bioinformatics and machine learning to analyze gene expression from microarray or RNA-seq data. While AMPEL’s platform can analyze RNA from any source, the CLIA-certified technique incorporated into the LuGENE assay is RNA-seq.
As of March, LuGENE is available at high-volume lupus treatment sites around the country after the company released an early-access version of the assay last year.
The company is now enrolling participants into the observational ReLATE study to determine the association between data obtained using LuGene and standard diagnostic evaluation of lupus. Currently, AMPEL is recruiting up to 200 adults at two sites in Charlotte, North Carolina, and Los Angeles, with more sites across the country due to open over the course of the year.
Grammer said that longitudinal data stemming from the company’s recent study indicates that LuGENE can predict the likelihood of flare-ups up to 18 months out, making it a yearly test that could significantly drive down patient hospital spending.
“The cost of a once-a-year LuGENE blood test is definitely worth the much bigger cost of the flare,” she said, which typically incurs “very heavy” emergency room costs. Grammer said that Ampel is “in discussion” with the US Centers for Medicare and Medicaid Services regarding LuGENE’s price.
Lupus patients, Grammer said, typically see their rheumatologist yearly or quarterly, depending on the severity of their condition. A prognostic assay such as LuGENE, she added, would help to tailor the frequency of those visits to the individual patient and enable physicians to develop more individually focused patient care plans.
Ampel is currently providing the LuGENE tests for the ReLATE study, while working towards Medicare reimbursement for predicting flares and identifying abnormal potential drug targets. The company hopes to secure reimbursement in the next 12 to 18 months.
Grammer said that AMPEL also continues to assess the effects of therapeutic regimens on the various SLE subtypes and has already generated some initial results.
While it remains too early to discuss those results in detail, she said, the company plans to submit an abstract to the American College of Rheumatology this summer for presentation at the organization’s international meeting in November.
Further down the pipeline
AMPEL has several other transcriptomic tests in its pipeline, all of which it is steadily shepherding to market.
The next LDT that the company plans to launch will be its DermaGENE skin biopsy assay for inflammatory status and abnormal drug targets for patients with psoriasis and eczema. Grammer said that the company expects to launch this test in the next 12 to 18 months.
The company also expects to launch WellGENE, a blood-based LDT meant to “evaluate health by predicting the inflammatory status of clinically healthy individuals,” sometime this year or next.
Grammer said that the company has preliminary data that WellGENE can predict insulin resistance “long before any other test identifies it,” and can predict early cardiovascular events, such as heart attack and stroke.
“Now we’re looking for collaborators around the country that have longitudinal datasets of healthy individuals across ancestries to help move that product along,” she said.
Further down its pipeline, Ampel is developing the NephroGENE test for kidney damage in patients with chronic kidney conditions such as lupus nephritis, as well as FibroGene, a blood test for gene expression signatures of fibromyalgia.
Last year, AMPEL published studies on both of those assays.
A proof-of-concept study in mice suggested that NephroGENE could catch signs of lupus nephritis before kidney damage occurrs, which could help pharma companies identify the right patient populations for drug trials. Grammer said that Ampel is “actively looking for strategic partners” to further develop NephroGENE.
A study examining FibroGENE inhibited , meanwhile, identified two distinct gene signatures for SLE, one of which appeared specific to patients experiencing fibromyalgia.
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