NEW YORK (GenomeWeb) – After acquiring startup ProstaGene in August, molecular diagnostics firm CytoDyn will commercialize ProstaGene's prognostic prostate cancer assay as part of the firm's push into the cancer diagnostic market.
Vancouver, Washington-based CytoDyn believes the prognostic tool — which determines if the tumor will grow slowly or aggressively — will help stratify patients' risk for their prostate cancer outcome and help streamline clinical decisions for downstream surgery, radiation therapies, or therapeutics.
Clinicians normally use tools such as PSA assays or needle biopsy with Gleason scores to detect cases of prostate cancer in patients with different risks for the condition. However, both tools normally have low predictive values and can lead to excessive prostatectomies and over-treatment with radiation.
While he was a researcher at Thomas Jefferson University, CytoDyn interim Chief Medical Officer Richard Pestell initially developed oncogene-specific prostate epithelial cancer cell lines that grew in immune competent mice. The university licensed the technology based on the oncogene biosignature to Pestell, who then founded and acted as CEO of ProstaGene in 2011. Pestell's team began developing therapeutics based on his work on the CCR5 gene as a potential target, separately developing the PCaTest for prostate cancer prognosis.
CytoDyn initially expressed interest in acquiring ProstaGene in July while sponsoring the firm's research on treatment using leronlimab (a CCR5 inhibitor drug CytoDyn originally developed), and made the move in August, with Pestell joining the company as CMO to further build on his work on the PCaTest and CCR5 gene. The acquisition is expected to close in the fourth quarter of this year.
CytoDyn's PCaTest is a 16-gene mRNA expression assay (including 14 specific genes and two housekeeping genes) that examines mRNA isolated from a prostate tissue biopsy. The company currently offers it as a laboratory-developed test. According to Pestell, a pathologist extracts the tissue from a patient and decides whether the sample is cancer positive or negative. If positive, PCaTest can then be used to stratify patients into different prognostic groups.
While initially developing the tool, Pestell said that the ProstaGene team transformed several normal prostate cells with oncogenes and then compared all the genes that were turned on or off. The team then developed "a massive artificial intelligence approach to [extract] a signature of prostate oncogenesis."
The firm whittled down the initial 60-oncogene signature to 16 and used that signature to interrogate clinical data samples, observing that "the greater the prostate cancer oncogenesis was, the worse the outcome was for the patients."
According to Pestell, the assay uses the algorithm based on the gene expression biosignature to produce a score that predicts a range of outcomes for a patient's prostate cancer prognosis. The score allows a clinician to make proper decisions for patient treatment and therapy.
"Right now, the hazard ratio [for prostate cancer] is pretty low, and the decision-making ability is relatively poor," Pestell explained. "We've developed a test where there's three independent retrospective studies that have shown a higher hazard ratio, allowing the doctor and patient to make [an] informed decision about the path forward."
Pestell said that PCaTest splits patients into different subsets, determining if their risk is severe enough for aggressive forms of therapy —such as prostatectomy or chemotherapy— or mild enough for immunotherapy or radiation therapies. However, he pointed out that the assay is not a primary diagnostic and should instead be used to further confirm the presence of prostate tumors or reduce the number of unnecessary prostatectomies.
While CytoDyn currently offers PCaTest as an LDT, Pestell said the firm aims to obtain CE marking and a 510(k) clearance from the US Food and Drug Administration. He also noted that the firm is currently in discussion with three companies to license the tool for commercial use, though he declined to disclose potential partners.
Pestell said that his team at ProstaGene initially dealt with two major technical limitations while developing PCaTest. First, the researchers struggled to accurately and reliably analyze the small amounts of tumor RNA. To solve this, Pestell's team decided to run the PCaTest on NanoString Technologies' nCounter Sprint platform to extract and amplify the relative abundance of the specific prostate cancer transcripts they could use per run.
"NanoString has a great platform, allowing you to detect lower levels of RNA, which is why we can use prostate cancer biopsies for mRNA," Pestell explained.
Pestell's team also had to figure out how to reliably "interrogate very large clinical databases of gene expression to deduce the smallest number of genes with the highest predictive value in multiple independent datasets." According to Pestell, CytoDyn will target newly detected cases of prostate cancer every year in the US as its initial market. CytoDyn believes clinicians could use the assay for male patients over the age of 40 who have received a digital rectal exam and an initial prostate biopsy based on abnormal levels of prostate-specific antigen, or who may have an increased risk based on family history and are thus a potential carrier of a prostate cancer predisposition mutation.
CytoDyn will be entering a busy US prostate cancer diagnostic space, as many companies already offer liquid- and tissue-based prognostic tools for patients with the disease.
Metamark Laboratories currently offers it Promark Prostate Cancer assay, an eight-marker panel that uses immunofluorescence to track levels of protein biomarkers in prostate biopsy tissue. Myriad Genetics' Prolaris Prostate cancer assay, which received a positive medical policy decision by an unnamed "top-five insurer" in June, uses 31 genes in its RNA expression panel and produces a cell cycle progression score for patients to predict tumor aggression.
GenomeDx's Decipher Prostate Cancer Classifier Test, which received coverage by Medicare last month, comprises a 22-gene RNA expression panel linked to aggressive prostate cancer. MDxHealth currently offers its ConfirmDx liquid-based bladder test, which uses methylation-specific PCR to  help doctors identify patients risks of cancer.
Pestell claims that the PCaTest will differ from competitors' assays because of its high hazard ratio, which indicates a better discrimination between a good and poor outcome for the patient. In internal studies the firm has demonstrated that its assay has a higher AUC than competing tests in three independent datasets comprising 348 total patient samples, though this data has not yet been published or presented at a scientific conference.
While Pestell declined to comment on the price for the PCaTest, he noted that the firm's goal will be to "underpromise but to overdeliver on its results."
Pestell noted that CytoDyn has started a retrospective study to examine the value-added benefit of the PCaTest, where the firm aims to demonstrate how the tool enhances the Gleason score of individual patients to potentially improve prediction of correct outcome. The study will examine several hundred patients with risks for the condition with long-term follow up. The company hopes to complete the study by Q1 2019. CytoDyn will also begin a clinical study designed to show the tool's "superiority compared to other commercial assays."