NEW YORK (GenomeWeb) – Immunovia recently announced a mixed bag of news concerning its pancreatic cancer assay.
Last month, the Sweden-based firm said that it has decided to push back the international commercial release of the IMMray PanCan-d assay due to sample collection issues encountered in a retrospective study. Just days later, it then said that a study describing work on the 29-biomarker signature comprising the test indicates it could potentially be used to detect early-stage pancreatic cancer.
In the commercial space, Immunovia now aims to launch the IMMray PanCan-d assay as a laboratory-developed test in the US by the end of 2019. It had previously targeted a late 2018 or early 2019 launch.
While performing the unpublished retrospective study, conducted as part of Immunovia's plans to commercialize the test worldwide, Immuovia's researchers discovered variations in biobank blood sampling processes, which introduced unexpected variability in the test's performance.
The study comprised a large undisclosed number of blood samples collected from five international biobanks, including groups from Sweden, Germany, Denmark, and the US, according to Immunovia Chief Commercial Officer Laura Chirica. The samples covered all stages of pancreatic cancer, combined with samples from patients presenting potentially early symptoms of pancreatic cancer and from healthy controls.
Because of different blood sampling processes that were used by the different biobanks, performance of the IMMray PanCan-d assay's algorithm varied, and when Immunovia examined the results, it "couldn't achieve the same performance that we wanted to have in this test, which needed a higher accuracy than 95 to 96 percent seen in previous studies," Chirica said.
Variations in the collection processes included the biobanks' use of different types of collection tubes and collection gels. Additionally, different extraction tools were used, and there were variable amounts of time between sample collection and freezing.
"Because [this was] a retrospective study, we had to take samples that were already stored at biobanks," Chirica said, and Immunovia realized it needed to perform additional studies to optimize the assay's algorithms and standardize the collection procedure in order to minimize any variations.
In August, the company began work to optimize the biosignature by "including antibodies that do not have variability in the signature," she said, and added the firm will "need a number of studies that take the factors," such sample collection techniques "into account and eliminate them."
"Unfortunately, we will need to take time to run the whole process again since you need to safeguard the quality of the cancer assay," Chirica said. "However, this time will be easier, since we will not need to search for the groups required [to perform] the verification, validation, and additional studies."
According to Chirica, Immunovia expects to complete the optimization studies by Q1 2019 and has decided to delay the commercial release of the IMMray PanCan-d assay until the second half of 2019.
"We will have more of an exact deadline for commercialization as we move forward with the optimization studies," she said.
The firm noted that the delay will cost it an estimated SEK 5 million ($568,337).
Despite the delayed timeline for commercialization, Chirica highlighted that the financial targets Immunovia previously adopted are unchanged. The firm aims to reach SEK 250 million to 300 million in revenues in 2022, based on "self-pay" sales, and revenues of SEK 800 million to 1 billion in 2024, which includes payments via self-pay and cost remuneration from insurance systems. At the same time, Immunovia expects to receive the first revenues from self-pay sales in the latter half of 2019.
Chirica said that Immunovia will initially market IMMray PanCan-d as a laboratory-developed test in the US, then as a CE-marked assay in Europe. Last year, the firm opened a US subsidiary in Boston to house commercialization operations as a CLIA reference laboratory. This past June, the firm raised $37.1 million to fund marketing and sales efforts, as well as continued development for its products.
Chirica expects IMMray PanCan-d to initially cost about $600. However, as volume increases and assay production improves, the price may change.
Not all bad news
While Immunovia has had to delay the launch of the Immray PanCan-D assay, last month it also reported positive study results for the assay, which it said could have use for the detection of early-stage pancreatic cancer.
Researchers typically use a variety of methods to detect early forms of pancreatic cancer, including circulating tumor cell (CTC) analysis and tissue biopsy. However, by the time that standard methods identify signs of pancreatic cancer, it may already have metastasized.
"What we [at Immunovia] look at is something earlier than circulating tumor DNA, as we instead examine the immune response," Immunovia Chairman Carl Borrebaeck explained. He believes that "circulating tumor DNA is aiming more for monitoring as the disease develops, rather than early detection."
In a study published in the Journal of Clinical Oncology, Borrebaeck and his team describe a biomarker signature derived from a Swedish cohort of about 1,350 patients, including samples from patients with well-defined early stage pancreatic ductal adenocarcinoma (PDAC): 16 samples were from patients with stage I disease; 132 were from stage II; 65 from stage III; and 230 from stage 4. Using the Scandinavian case-control study, Borrebaeck and his team developed the 29-gene signature for detecting stage I and stage II PDAC.
To decipher a condensed biomarker signature, Borrebaeck and his team divided the data into a "training set including three quarters of the samples and a test set including one quarter of the samples."
The researchers analyzed individual biomarkers that displayed a temporal expression pattern linked to progression from stage I to stage IV. By examining the data with multigroup analysis of variance, the team identified several biomarkers that were differentially expressed in patients with early- versus late-stage PDAC, including disks large homolog 1, PR domain zinc finger protein 8, and membrane-associated guanylate kinase, WW and PDZ domain-containing protein.
Because intraductal papillary mucinous neoplasms (IPMNs) often progress to invasive cancer if not quickly treated, the team decided to apply the consensus signature to discriminate different stages of IPMN versus controls. They saw that the IMMray PanCan-d assay classified the malignant IPMNs as having a cancer profile, whereas borderline and benign IPMNs were classified as non-PDAC.
To obtain a consensus signature with the best accuracy, the team combined all classifications of controls versus PDAC, then validated the signature in an independent case-control group of US patients with stages I-IV PDAC and controls.
Borrebaeck and his team found that the biomarker signature could discriminate patients with stage I and II PDAC controls in the Swedish cohort, with a clinical sensitivity of 93 percent and specificity of 95 percent.
"The aim of the study was not to be biased by previously defined biomarkers, as many of them were bad biomarkers," Borrebaeck explained. "In the end, however, there were maybe five to seven who contribute the best on their own, but the others are considered [because] they improved the accuracy from 90 to 96 percent."
However, the researchers noted that multiple limitations exist with the biomarker signature developed in the two-part study. First, because the signature was developed using case-control studies, they are unable to guarantee how effectively it will function in a surveillance or therapeutic setting until they perform additional validation studies. Since the researchers collected blood samples at the time of diagnosis, they noted that they could not predict how the signature would perform in patients after tumor resection.
The team also noted that while the study included patients with known disease statuses, the signature might not always perform as well in prediagnostic samples. However, Borrebaeck said his team has already begun prospective studies to examine if the IMMray PanCan-d tool can be used to diagnose pre-symptomatic patients with a familial or hereditary association with pancreatic conditions.
He also noted that Immunovia's diagnostic tool differs from current assays on the market because it examines immune-based biomarkers, rather than searching for circulating tumor cells in the patient's bloodstream.
According to Borrebaeck, researchers who perform CTC detection must "have an established tumor, which might be too late [to effectively treat the patient], as the tumor cells might have metastasized or gone through the bloodstream. In addition, you need up to 300 milliliters of blood for the [CTC] assay, since the assay's sensitivity is so low."
He and his team believe the serum biomarker signature they've developed into an potential diagnostic assay — while now delayed until 2019 — could represent an approach to detecting early-stage, localized PDAC.