Glencoe: Transforming Pathology Workflows for Regulatory Success using OMERO Plus and PathViewer

Glencoe Software and CymaBay Therapeutics collaborated to digitally transform a pathology review workflow, which delivered on an NDA-enabling clinical trial requirement ahead of schedule.

CymaBay Therapeutics, acquired by Gilead Sciences, developed a novel, pioneering treatment for liver Primary Biliary Cholangitis (PBC). The molecule, seladelpar, a selective PPAR delta agonist, was previously halted for all development efforts due to “unexpected” liver pathology observed in a Phase 2 NASH trial. As part of the NDA-enabling trial for PBC, the FDA required liver biopsies to ensure that seladelpar didn’t cause any liver pathology. A critical part of this work was a collaboration with an independent Pathology Review Committee (PRC)—a team of experts with deep knowledge in liver histopathology in PBC patients. The PRC’s role was to provide accurate, blinded, independent scoring of liver biopsy images.

However, viewing, sharing and annotating the large volume of complex data involved in these studies presents unique challenges. CymaBay turned to Glencoe Software to transform their Digital Pathology review workflow, which enabled the PRC to deliver reviews faster and with greater precision, in particular due to improvements in consensus determination.

Challenges in pathology workflows

In any regulatory study, the accuracy and independence of pathology scoring are paramount. The PRC, composed of highly experienced pathologists, needed a way to review thousands of high-resolution images efficiently without introducing bias or compromising on quality. Traditional methods often involved downloading data locally, which was not only time-consuming but also introduced potential inconsistencies in how images were viewed and scored. Further, because local review was not reproducible, disagreements between pathologists on scoring were challenging to resolve.

Additionally, ensuring unbiased results was crucial. Past experience had shown that even minor influences of additional information displayed alongside the slide image could skew pathology scoring, leading to potentially incorrect conclusions. This made blinding a core requirement of the workflow.

Enabling intuitive, accurate and efficient review with OMERO Plus and PathViewer

Backed by Glencoe Software’s data management platform OMERO Plus, PathViewer enables review without downloading massive datasets. All work can be done within a web browser, with images hosted securely online and instantly available. The study at hand involved over 7,000 images, amounting to more than 1.2 TB of data. These images were incredibly detailed, with resolutions averaging 22,000 x 18,000 pixels. Managing such large datasets was a critical challenge, which OMERO Plus and PathViewer handled effortlessly.

CymaBay’s workflow evolved dramatically with the integration of OMERO Plus and PathViewer, bringing a new level of efficiency and accuracy to the PRC’s operations. Whether pathologists were in their labs or traveling, PathViewer allowed them to access and review images remotely. This level of flexibility greatly reduced the turnaround time for pathology reviews, ensuring that critical decisions could be made faster. As a result, the PRC not only met their aggressive 16-week deadline, but completed their work a week early.

Importantly, PathViewer’s intuitive interface made it accessible even to pathologists who were not previously familiar with the tool or with digital review in general. One critical feature of PathViewer was blinded annotation mode, which allowed each pathologist to independently mark up liver biopsy images without seeing each others’ annotations. This ensured that every pathologist was presented with a clean canvas when reviewing and scoring the tissue samples. The study administrator could then confidently review scores and annotations in aggregate, making it easier to identify discrepancies and facilitate discussions when scores diverged.

As part of the study, many of the subjects had paired biopsies, one taken prior to the subject commencing their blinded treatment and another biopsy taken after a year. Part of the scoring process involved a side-by-side comparison of whether one biopsy was similar to or different than the other. PathViewer GRID seamlessly enabled these comparisons of tissue sections at their full resolution.

Conclusion

For the CymaBay Pathology Review Committee, the combination of OMERO Plus and PathViewer not only streamlined their workflow but also ensured that the data remained unbiased, well-managed, and accessible. The ability to review high-resolution images efficiently, while maintaining the scientific integrity required for regulatory approval, was key to CymaBay’s deliverables in this study. The independent blinded assessments provided clear data that the study drug, seladelpar, did not produce any additional pathology within the livers of PBC patients. This was a key safety question of concern to the FDA, especially since other PPAR agonists, are contraindicated in patients with hepatic impairment. Having an additional therapeutic option for PBC patients that are unresponsive to the first-line treatment is an important step for this patient group.

By integrating these tools into their operations, CymaBay has demonstrated their commitment to leveraging innovative technology to ensure accurate clinical outcomes. OMERO Plus and PathViewer will continue to play a vital role in supporting future regulatory studies, offering a powerful solution to any organization facing similar challenges.

SOURCE: Glencoe Software