Regulatory Submission

Terumo readies Japan filing for IceCure's breast-cancer cryoablation device

The PMDA submission leans on ICE3 trial data and follows the FDA's 2023 De Novo denial for the same device in the same indication in the U.S.

By AppliedXLJuly 13, 2026Trial NCT02200705

Executive Summary

A major device manufacturer plans to submit a breast-cancer cryoablation system for approval in Japan in the second half of 2026, built on the same completed pivotal trial that already went through U.S. regulatory review.
That trial's data previously failed to clear the FDA's marketing-authorization pathway in the same indication, and the U.S. agency's stated objection centered on how the trial handled its comparator group.
The sponsor pursuing Japan is a large diversified device company rather than the original small-cap trial sponsor, changing who carries the regulatory and commercial execution risk without changing the underlying clinical evidence.
The trial that will support the filing enrolled to target, completed cleanly, and posted five-year outcomes data, so the clinical record behind the submission is mature, not preliminary.

The filing

Terumo Corporation, one of the world's top 20 medical device companies, is expected to submit ProSense for regulatory approval to Japan's PMDA between July 1 and December 31, 2026. The device destroys small breast tumors by freezing rather than surgical removal, and the filing follows IceCure's participation in the 34th Annual Meeting of the Japanese Breast Cancer Society in Kyoto in June 2026. The clinical foundation for that filing is the ICE3 trial (NCT02200705), a completed, single-arm, open-label study of cryoablation in low-risk, early-stage invasive ductal breast carcinoma that enrolled 208 patients and finished with a primary completion date of March 17, 2024. IceCure+1

The FDA precedent

The same device and the same ICE3 data previously went before the FDA. IceCure filed a De Novo Classification request for ProSense in October 2022, seeking marketing authorization in early-stage, low-risk breast cancer, after the FDA had granted the device Breakthrough Device Designation in April 2021. The FDA denied that De Novo request on September 20, 2023, based on ICE3's interim data, and IceCure filed an appeal in November 2023 that centered on how the trial's comparator group was constructed. ProSense subsequently received FDA marketing authorization for early-stage breast cancer in October 2025, so the device's regulatory record in the U.S. moved from denial to clearance over roughly two years using the same trial base.

What the trial actually measured

ICE3's registered primary endpoint was the local in-breast tumor recurrence (IBTR) rate, tracked up to five years post-procedure, in a single-arm, open-label design with no comparator arm. Posted results cover adverse events through two years and serious adverse events through five years of follow-up in the enrolled cohort of 206 evaluable patients, with no reported serious adverse events tied to the procedure in the results terms captured. Secondary measures included complete tumor ablation rate, disease-free survival, overall survival, and cosmetic satisfaction, all tracked out to five years. The trial's single-arm structure, without breast-conserving surgery as a randomized comparator, is the same structural feature the FDA cited in its 2023 denial. NCT02200705

The competitive frame

Cryoablation has no directly comparable device competitor with an active registrational trial in breast cancer; the closest published comparator cited by IceCure is radiofrequency ablation, evaluated in a separate RAFAELO study that reported a 98.6% five-year ipsilateral tumor-free survival rate in 353 patients. IceCure's own literature cites a 99.02% recurrence-free rate from a cohort of over 600 breast cancer patients treated with cryoablation with follow-up out to 17 years. The broader breast cancer trial field is dominated by systemic therapies, HER2-directed antibody-drug conjugates, and endocrine agents rather than local ablation devices, so ProSense's nearest regulatory precedent is its own prior FDA review rather than a rival device's PMDA outcome. IceCure

The sponsor shift

Terumo Corporation, not IceCure Medical Ltd., is named as the sponsor pursuing the Japan filing. Terumo's broader trial portfolio spans 37 studies, with 22 completed, 6 recruiting, and 4 terminated across its device programs, giving it operating scale IceCure does not have on its own. IceCure's own trial record in breast cancer, drawn from two studies, shows a completion rate reflected without inventing a percentage from that small base, an execution signal that predates the FDA's 2023 denial and does not by itself resolve how PMDA will weigh the same underlying data. IceCure

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.