CLBS12 Granted Orphan Designation for Thromboangiitis Obliterans

David J. Mazzo, PhD

The FDA has granted an orphan drug designation to CLBS12 as a potential treatment for patients with thromboangiitis obliterans (TAO), also known as Buerger disease, according to a statement from Caladrius Biosciences, the developer of the CD34+ cell therapy product.

The orphan drug designation is intended for products that treat rare diseases or conditions and was established under the Orphan Drug Act. The designation provides a number of incentives, according to the FDA, including tax credits for qualified clinical testing. Moreover, a company developing an orphan product is not required to pay prescription drug user fees when submitting a marketing application for the designated indication.

“We are very pleased that the FDA has granted orphan drug designation to CLBS12 in Buerger’s disease. Without a currently approved or effective treatment for this condition in the United States, a significant unmet need remains for therapies that slow, stop or, ideally, reverse this debilitating disease,” David J. Mazzo, PhD, president and chief executive officer of Caladrius, said in a statement.

CLBS12 consists of autologous CD34+ harvested from peripheral blood by apheresis following mobilization using with the G-CSF agent filgrastim. Once collected, the cells are administrated through an intramuscular injection of up to 1 x 10⁶ cells per kilogram per impacted limb.

CLBS12 is currently being examined in an open-label phase 2 study enrolling in Japan, where it is known as Honedra. This randomized study is examining the treatment in patients with critical limb ischemia (CLI) due to arteriosclerosis obliterans (ASO). Additionally, an arm of the study is assessing the therapy in patients with CLI due to TAO. All patients had a Rutherford score of 4 or 5 at entry. Overall, the study has enrolled 30 patients with CLI and no other options and 7 patients with TAO.

All patients enrolled in the study are receiving standard of care therapy, including antiplatelets, anticoagulants, and vasodilators. In the CLI arm related to ASO, patients are randomized to standard of care alone or with CLBS12. In the single-arm TAO portion of the study, all patients will receive CLBS12 plus standard of care (NCT02501018).

Findings from the study were delayed by COVID-19; however, the company released early data noting that 4 of 7 patients with TAO treated with CLBS12 were free of CLI, defined as a Rutherford score ≤3 by the investigator and a central adjudication committee. Based on full findings from the study, Caladrius hopes for a rapid approval and commercialization in Japan by the middle of 2022. The first patient was dosed in the trial in March 2018.

“The company’s ongoing open-label, registration-eligible study of Honedra (CLBS12) as a treatment for CLI and Buerger’s Disease in Japan has shown strong results to date, with approximately 60% of subjects in the completed Buerger’s Disease cohort reaching a positive ‘CLI-free’ end point despite the natural history of continuous disease progression leading to amputation," Mazzo said.

Development of the agent has not yet begun in the United States. With the orphan drug designation, Caladrius plans to broaden its development program. In addition to CLBS12, the company is also exploring CLBS16, also a G-CSF-mobilized CD34+ cell therapy, in a phase 2 study known as FREEDOM within the United States for patients with coronary microvascular dysfunction (NCT04614467).

"With this designation we can now engage FDA in discussions to define the most efficient and rapid development pathway to registration in the United States," said Mazzo. "Achieving orphan designation for CLBS12 takes us one step closer to realizing our goal of fulfilling the unmet medical need for Buerger’s Disease patients around the world.”