NEW YORK – Despite inconclusive results from a study evaluating its pancreatic cancer test, Swedish diagnostic firm Immunovia is largely staying the course and continuing with its US reimbursement efforts.
The Lund University spinout announced earlier this week that results of the PanFAM-1 study were partly inconclusive, as sensitivity of the ImmRay PanCan-d test couldn't be evaluated due to the low number of pancreatic ductal adenocarcinomas (PDACs) among participants.
The serum-based multiplex test relies on eight biomarkers to obtain a disease biomarker signature. It uses single-chain, variable-fragment antibodies attached to resin-coated slides in a microarray to detect the biomarkers and determines the concentrations by decoding signal intensities from the microarray. Immunovia launched ImmRay PanCan-d in the US as a laboratory-developed test last year after multiple delays.
The PanFAM-1 study was intended to determine both the sensitivity and specificity of ImmRay PanCan-d compared to clinical imaging, which "is the standard of care for surveillance for pancreatic cancer in high-risk individuals," Immunovia Medical Director Thomas King said on a conference call to discuss the results.
Enrollment for the prospective, multicenter study began in January 2016 and closed last November, with a total of 1,255 qualified subjects enrolled. It was planned as a two-phase trial with an observational study before the test was available followed by an interventional phase. However, that interventional phase never occurred, due to "delays in the clinical launch" of the test, King said.
Some of the issues with the study were the result of the COVID-19 pandemic leading to "quite a few deviations from the plan," King said.
The patients enrolled in the study were originally supposed to undergo imaging at least once per year and have blood samples collected every six months throughout the trial, but the COVID-19 pandemic impacted collection efforts and the 3,457 blood samples Immunovia collected were "substantially less" than intended, King said. More than half of the patients had two or fewer blood samples collected — full study participation over four years would have resulted in nine samples per person.
There were also significant delays in study approvals at multiple sites, and many sites were not able to join the trial for the full five years, he said.
Parts of the study's design also contributed to the inconclusive results, he added. Patients were allowed to enroll at a "fairly young age" compared to when pancreatic cancer develops — most of the patients were younger than 70, which is the median age for pancreatic cancer development.
"Age is a very important risk factor for pancreatic cancer, as is family history and germline mutations," King said. "In some ways, we kind of stacked the deck so that we would find fewer cancers."
The firm also likely overestimated the prevalence of PDAC in the population it studied, expecting 2.5 percent of patients would develop cancer. Only three out of the 1,255 patients enrolled — less than 1 percent — developed PDAC, so the sensitivity wasn't able to be determined. Out of those three patients with cancerous tumors, the test was able to detect two.
The test's specificity compared to imaging, however, was 98 percent in North American participants. That specificity aligns with the values found in Immunovia's previous blind validation study published earlier this year in Clinical and Translational Gastroenterology, King noted. The PanFAM-1 study also confirmed the test's 99 percent negative predictive value in a high-risk screening population.
Jeff Borcherding, CEO of the firm's Immunovia US subsidiary, said on the call that the company is planning to generate additional clinical data for the test. To that end, the company has already launched its six-month Pioneers Physician Experience Program in the US to provide free ImmRay PanCan-d tests to providers and patients in high-risk surveillance programs. To participate, patients must agree to provide their imaging reports to Immunovia for comparison with the test results, Borcherding said. The program is generating real-world evidence and allowing the company to get provider feedback on the utility of the test via surveys, he added.
The firm is also considering real-world evidence studies, such as retrospective database studies or prospective registry studies, which can be executed more quickly than more extensive studies, he said.
Immunovia has had conversations with US payors about conducting demonstration pilot programs to demonstrate clinical utility within a certain payor's population, he added. Some insurers may pay for the tests used in those studies, allowing the firm to generate revenue before it has "formal positive medical policy decisions" from those payors, Borcherding said.
"We want to continue to build the evidence for the clinicians that we are talking to about using ImmRay PanCan-d," he said. "We'll use that to further our conversations with payors about generating medical policy decisions and securing reimbursement coverage for ImmRay."
Borcherding also laid out the rest of the US reimbursement plan for the test. In April, the firm submitted the test for a PLA code to facilitate payment once the test receives insurance coverage and Borcherding said the firm has received "early indications" that the code will be issued in January 2023. The company has also submitted data to the US Centers for Medicare and Medicaid Services to suggest an appropriate price for the test once it receives reimbursement coverage, which Borcherding called "an important milestone" as the firm moves forward.
The firm currently anticipates initial commercial reimbursement in either Q4 2022 or in 2023.
Despite the PanFAM-1 results, Borcherding said he thinks the methods Immunovia has for generating additional data will support its reimbursement efforts and that payors will understand the impact of COVID-19 on the study. He added that the study's specificity findings will be important for payors because it "helps them to gain confidence that we will not be putting patients through additional workups that cause anxiety and lead to additional cost."
"We're certainly doing everything we can to minimize any delays in reimbursement as a result of this study," he said.