A majority of the US Food and Drug Administration’s Medical Imaging Drugs Advisory Committee (MIDAC) on March 5 voted in support of LUMISIGHT’s (pegulicianine) benefit-risk profile.
LUMISIGHT is an optical imaging agent used in combination with Lumicell Direct Visualization System (DVS), a fluorescence-guided imaging system. The technology, developed by Lumicell Inc., helps surgeons identify cancer that may remain in the breast after they’ve completed the main resection of tissue.
Following MIDAC’s positive vote, the FDA will move on to reviewing Lumicell’s new drug application for LUMISIGHT and its premarket approval application for Lumicell DVS.
“We are proud of the efforts and look forward to the next steps as we work with the FDA to finalize the approval process so that women with breast cancer can access the therapy,” Jorge Ferrer, PhD, Lumicell’s chief scientific officer, said in an interview.
However, Freya Schnabel, MD, professor of surgery and director of breast surgery at NYU Perlmutter Cancer Center, said there are some “real concerns” with the technology. She expressed surprise at MIDAC’s overall favorable vote.
In a recently published study, she noted that the use of pegulicianine fluorescence-guided surgery (pFGS) did not meet the prespecified threshold for sensitivity.
“It did meet thresholds for removal of residual tumor and specificity — but this is still basically a negative study, and a low sensitivity raises concerns regarding false negative readings,” she said in an interview. “I’m surprised [the committee] is supportive in light of this result. Also, the technique is logistically challenging, as patients need to be injected 2 to 6 hours before their surgeries, very challenging timing for patients having ambulatory procedures.”
The study, published in the April 2023 NEJM Evidence, analyzed 357 patients who received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Tumor left behind after standard lumpectomy was removed in 27 of 357 patients through use of pFGS. Of the 27, 22 patients had cavity orientations deemed “negative” on standard margin evaluation, according to the study. A margin is described as negative or clean when there are no further cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins, the analysis found.
On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. While the sensitivity endpoint missed the lower boundary of the 95% confidence interval, the LUM system exceeded the specificity endpoint of 60% with a point estimate of 86%, and an accuracy of 84% for imaging residual cancer in the lumpectomy cavity, coinvestigator E. Shelley Hwang, MD, MPH, said during the MIDAC meeting.
“The pivotal study was an adequate and well-controlled study demonstrating the effectiveness of the LUM system to detect residual cancer in the lumpectomy cavity, following the standard of care procedure,” she said. “These results also demonstrate clinical benefit that improves the current standard of care. This is the first and only imaging system that provides results in the lumpectomy cavity in real time, allowing surgeons to use this information at the time of the initial procedure.”