Alpha Tau Submits First PMA Module to FDA for Novel cSCC Treatment, Alpha DaRT

This month, Alpha Tau Medical has announced the submission of the first module of its Pre-Market Approval (PMA) application to the US Food and Drug Administration (FDA) for Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) for the treatment of recurrent cutaneous squamous cell carcinoma (cSCC).¹ This milestone represents a significant regulatory step toward potential marketing authorization for a novel, intratumoral alpha-radiation therapy intended for patients with limited therapeutic options.

“Alpha Tau continues its fast pace of activity, charging forward in our pursuit of potential marketing authorizations across a wide range of tumors, with an eye toward future commercialization. The decision by the FDA to allow us to submit our PMA in a modular form will hopefully allow for ongoing FDA review and feedback as each module is submitted, and we look forward to this dynamic and efficient authorization review process with the FDA,” Uzi Sofer, CEO of Alpha Tau, said in a statement.¹

ReSTART Clinical Trial

This regulatory submission is occurring in parallel with the company’s ongoing pivotal clinical trial, ReSTART (Recurrent SCC Treatment with Alpha DaRT Radiation Therapy), a multicenter study evaluating Alpha DaRT in approximately 86 patients with recurrent cSCC.² Primary end points include the objective response rate and duration of response, while secondary end points include progression-free survival, overall survival, time of local control, quality of life, adverse effects, and user experience. Enrollment in ReSTART (NCT05323253) is expected to be completed in the first quarter of 2026. Alpha Tau is simultaneously conducting 4 additional clinical studies in the US exploring Alpha DaRT across other solid tumor indications.

Regulatory Support

Notably, Alpha DaRT has received Breakthrough Device Designation from the FDA for recurrent cSCC, as well as for recurrent glioblastoma multiforme and recurrent squamous cell carcinoma of the oral cavity. The company is also participating in the FDA’s Total Product Life Cycle Advisory Program (TAP) for recurrent glioblastoma, which is designed to accelerate patient access by fostering earlier and more frequent engagement between developers and regulators.

A New Approach to Radiotherapy

Alpha DaRT represents a novel approach to radiotherapy that differs fundamentally from conventional external-beam or brachytherapy techniques. The technology involves the intratumoral insertion of small radium-224-impregnated sources directly into the tumor. As radium-224 decays, it releases short-lived daughter isotopes that emit high-energy alpha particles. These alpha emitters diffuse only a very short distance, allowing for highly potent and localized radiation delivery intended to destroy tumor cells while sparing surrounding healthy tissue.

Addressing Unmet Needs in Recurrent Skin Cancer

“Recurrent skin SCC poses a unique challenge, particularly in elderly patients or those with extensive prior radiation, where surgery is no longer an option. Historically, we have lacked tools that offer both aggressive local control and minimal toxicity. Alpha DaRT fills that void,” Robert B. Den, MD, Chief Medical Officer of Alpha Tau, told Dermatology Times.

It is the first localized anticancer therapy to utilize the specific therapeutic properties of alpha particles and can be administered through a minimally invasive outpatient procedure. Other potential advantages include higher cancer kill rates while sparing healthy surrounding tissues, potential immune response stimulation, reduced radiation exposure, and broad applicability across various tumor types.

“Its ability to deliver potent, localized alpha radiation directly into the tumor bed allows us to be more aggressive against the cancer than ever before, while remaining conservative with the surrounding healthy skin. It is a vital new addition to our armamentarium for cases that were previously considered 'untreatable,’” Den said.

References

1. Alpha Tau Submits First Pre-Market Approval Module to the FDA for Alpha DaRT® for the Treatment of Recurrent Cutaneous Squamous Cell Carcinoma (cSCC). News release. Alpha Tau. Published January 5, 2026. Accessed January 13, 2026. https://www.alphatau.com/single-post/alpha-tau-submits-first-pre-market-approval-module-to-the-fda-for-alpha-dart-for-the-treatment-of-r

2. Alpha Tau Announces Alpha DaRT™ Treatment of First Two Patients in its Pivotal Multicenter Recurrent Skin Cancer (ReSTART) Trial. News release. Alpha Tau. Published March 12, 2023. Accessed January 13, 2026. https://www.alphatau.com/single-post/treatment-of-1st-two-patients-in-its-pivotal-multicenter-recurrent-skin-cancer-restart-trial