A new drug application for pafolacianine sodium injection was granted priority review by the FDA for use in detecting ovarian cancer lesions during surgical procedures.
The FDA has accepted and granted priority review to a new drug application (NDA) for pafolacianine sodium injection (OTL38) for use in identifying ovarian cancer during surgical procedures, announced the agent’s developer On Target Laboratories, Inc.1
Pafolacianine sodium is a fluorescent marker made of near-infrared dye and a ligand that allows it to bind to receptors overexpressed in ovarian cancer cells. When injected, the agent binds to folate receptors and will illuminate when used under near-infrared light. This unique mechanism of action allows for greater confidence that surgery resulted in a complete resection.
“Our NDA is supported by our positive phase 2 and phase 3 clinical trials,” Christopher Barys, President and CEO of On Target Laboratories, said in a press release. “As we move closer to FDA approval for ovarian cancer, we are realizing our mission to intra-operatively visualize more cancer and extend the benefits of a complete resection to patients.”
Strategies for identifying cancerous from noncancerous tissue during surgery for ovarian cancer are currently limited. The priority review will allow for this application to be reviewed over a 6-month period versus the standard 10 months.
Pafolacianine sodium injection previously received both fast track and orphan drug designation and was investigated under the Special Protocol Assessment, which “indicates concurrence by FDA with the adequacy and acceptability of specific critical elements of overall protocol design (eg, entry criteria, dose selection, end points, and planned analysis) for the study intended to support a future marketing application.”2
Results of a phase 2 trial that used pafolacianine sodium as an intraoperative adjunct were published previously in Gynecologic Oncology in 2019.3 The prospective trial assessed the safety and efficacy of the agent for intraoperative imaging during surgery for epithelial ovarian cancer.
The safety population was comprised of 44 patients and 225 lesions in 29 patients were evaluated to determine efficacy. Sensitivity was estimated to be 85.93% (95% lower boundary CI, 81.19%); positive predictive value (PPV) was determined to be 88.14% (95% lower boundary CI, 83.59%). Sensitivity and PPV were estimated to be 97.97% (95% lower boundary CI, 87.75%) and PPV at 94.93% (95% lower boundary CI, 86.13%) when controlling for actual correlation of detection among several lesions in a single patient. Notably, almost half (48.3%; 95% CI, 0.29-0.67) of patients had at least 1 more lesion detected by use of pafolacianine sodium alone.
All patients treated in the study had at least 1 treatment-emergent adverse event (TEAEs), with the most common being procedural pain within 1 to 2 days of surgery in 40 out of 44 patients (90.9%). However, none of these were considered to be related to the study drug.
TEAEs related to the study drug were reported in 8 patients (18.2%), the most common being gastrointestinal disorders in 5 patients (11.4%), specifically nausea (9.1%), vomiting (6.8%), and abdominal pain (2.3%). Infusion-related reactions occurred in 5 (11.4%) and sneezing/increased lacrimation occurred in 1 patient (2.3%).
Pafolacianine sodium injection is injected as a single-dose intravenous infusion prior to surgery. The agent is also being explored in the phase 3 ELUCIDATE trial (NCT04241315) for patients with lung cancer in the United States.
1. On Target Laboratories announces U.S. FDA acceptance and priority review of new drug application for pafolacianine sodium injection for identification of ovarian cancer during surgery. News release. On Target Laboratories, Inc. March 3, 2021. Accessed March 4, 2021. https://prnmedia.prnewswire.com/news-releases/on-target-laboratories-announces-us-fda-acceptance-and-priority-review-of-new-drug-application-for-pafolacianine-sodium-injection-for-identification-of-ovarian-cancer-during-surgery-301239430.html
2. Special Protocol Assessment, guide for industry. FDA. April 2018. Accessed March 4, 2021. https://www.fda.gov/media/97618/download
3. Randall LM, Wenham RM, Low PS, Dowdy SC, Tanyi JL. A phase II, multicenter, open-label trial of OTL38 injection for the intra-operative imaging of folate receptor-alpha positive ovarian cancer. Gynecol Oncol. 2019;155(1):63-68. doi: 10.1016/j.ygyno.2019.07.010