IceCure’s ProSense Denied FDA De Novo Classification for Breast Cancer

September 20, 2023—IceCure Medical Ltd., developer of the ProSense system for minimally invasive cryoablation treatment of tumors, announced that the FDA denied the company’s de novo classification request for ProSense to treat breast cancer that was submitted based on interim analysis from its ICE3 study.

IceCure filed the de novo request with the FDA in October 2022. The company stated it is pursuing all avenues to address the FDA’s response.

ICE3 is a controlled multicenter clinical trial for liquid nitrogen (LN2)–based cryoablation of small, low-risk, early-stage (Luminal A T1 invasive) malignant breast tumors without subsequently removing them. Patients in the trial are at high risk for surgery. Enrollment, which began in 2014, has included 194 eligible patients at 19 hospitals and medical centers across the United States.

In April 2022, the company announced the presentation of interim data by ICE3 trial coprincipal investigator Kenneth R. Tomkovich, MD, at ECIO 2022, the European Conference on Interventional Oncology in Vienna, Austria.

In the press release, the company noted that based on the last interim results released on October 19, 2022, there have been six (3.09%) cases of ipsilateral breast tumor recurrence (IBTR) out of 194 patients.

The survival-based estimate for the 5-year IBTR is 4.3% with a one-sided 95% confidence level, upper bound of 8.4% for the entire study. One-third of patients have reached 5 years post treatment. Additionally, to date, there have been no significant device-related adverse events reported with no scarring or change in shape and size of the breasts, while 100% of doctors and 100% of patients reported satisfaction with the cosmetic results.

IceCure is continuing the ICE3 clinical study, which is expected to be completed during the first quarter of 2024.

The ProSense system was granted an FDA Breakthrough Device designation in March 2021, and has received clearance in the United States for general minimally invasive cryoablation applications, including kidney, liver, and benign breast tumors. ProSense is approved for the treatment of malignant breast tumors in other jurisdictions, including Europe, China, and Brazil.

The company advised that the FDA’s position for breast cancer does not affect ProSense’s FDA clearance for other indications in the United States, where patients will continue to have access to ProSense for those treatments. Adoption of ProSense outside of the United States continues to build, noted IceCure.

Eyal Shamir, Chief Executive Officer of IceCure, explained in the press release, “The positive expected 5-year results based on the interim analysis of the ICE3 trial, which demonstrated a survival-based estimate for the 5-year IBTR of 4.3%, allowed us a rare and unique opportunity to submit a de novo classification request and make our minimally invasive ProSense cryoablation procedure available to women sooner for this important and underserved indication.

“We, along with our regulatory consultants, believe the FDA’s response to the de novo classification request is largely due to the FDA’s need for additional scientific literature as a comparator rate of recurrence in patients treated with lumpectomy. We are committed to working with the FDA to address its comments by using the broadly available published scientific literature on recurrence outcomes in patients treated with lumpectomy.”

“ProSense remains available in the United States under prior FDA clearances, and we will continue to execute our plan and progress toward achieving our primary objective of completing the 5-year follow-ups with our last patients in the ICE3 study by the first quarter of 2024, while we simultaneously evaluate all strategies to efficiently and effectively address the FDA’s comments,” concluded Shamir.