Caladrius Biosciences (CLBS) Suspends Patient Enrollment in Phase 2b FREEDOM Trial of XOWNA

Caladrius Biosciences, Inc. (Nasdaq: CLBS) today announced that the Company has suspended patient enrollment in its Phase 2b study of XOWNA^®, known as the FREEDOM Trial, for the treatment of coronary microvascular dysfunction (“CMD”). The Company intends to conduct an interim analysis of the data from not less than the first 20 patients enrolled using the 6-month follow-up data to evaluate the efficacy and safety of XOWNA^® in subjects with CMD and corroborate the ESCaPE-CMD study results. Additionally, the data from the analysis is expected to provide an indication of the magnitude of the XOWNA^® effect size on the clinical endpoints likely to be required by the FDA in a future pivotal study. Per good clinical practice, Caladrius will continue to assess and follow all treated subjects according to protocol through completion of follow-up. The interim analysis is expected to be completed in August 2022 and the next steps in development of XOWNA^® will subsequently be determined after appropriate regulatory and business review, expected to be announced prior to year-end 2022.

The FREEDOM Trial was originally designed as a 105-patient double-blind, randomized, placebo-controlled trial to further evaluate the efficacy and safety of intracoronary delivery of autologous CD34+ cells (XOWNA^®) in subjects with CMD and without obstructive coronary artery disease and was expected to complete enrollment in approximately 12 months. The primary objectives of the FREEDOM Trial were to corroborate, in a controlled trial, the results of the ESCaPE-CMD trial, a Phase 2a open-label, proof-of-concept study in CMD patients, to get a better estimation of the treatment effect size of XOWNA^® on clinical endpoints likely to be required by the FDA in a pivotal trial, and to assess the impact of XOWNA^® on a patient population more broadly representative of the intended commercial population. As previously communicated, enrollment in the FREEDOM Trial initially proceeded as planned with the first patient treated in January 2021; however, the impact of the COVID-19 pandemic in the U.S., coupled with supply chain issues associated with the catheters used for diagnosis of CMD and/or administration of XOWNA^® as well as with a contrast agent typically used in many catheter laboratories, have made and continue to make enrollment much slower than originally predicted and challenging to accelerate. Despite the multiple protocol amendments to address these obstacles, along with an increased number of sites in the study, the FREEDOM Trial has only enrolled approximately one third of the targeted 105 patients, and at this rate, more than four years would likely be required to reach the primary endpoint follow-up at 6 months post-treatment for all subjects. The Company believes that this revised timeline is not viable for financial and commercial reasons and an alternative development plan must be considered. As a result, the Company has suspended further enrollment activities and will conduct an interim analysis of the data to determine the next steps for the program.

“We have concluded that it is in the Company’s best interest to suspend enrollment in the FREEDOM Trial and complete an interim analysis of the data from the subjects enrolled to date, which we expect will provide meaningful insight on the best future clinical development pathway of the program,” stated David J. Mazzo, Ph.D., President and Chief Executive Officer of Caladrius. “Since the inception of the FREEDOM Trial, new technology has been introduced and validated for the diagnosis of CMD, yet these new techniques are not widely available nor are the associated diagnostic parameters widely accepted. Further compounding the situation is the discontinuation by the manufacturer of the diagnostic equipment that was originally specified in the trial to qualify patients for the study, discontinuation and/or supply shortages of catheters qualified for XOWNA^® administration and supply shortages of a contrast agent commonly employed in many catheter laboratories. These complications, coupled with the impact of the COVID-19 pandemic in the U.S., have made incremental enrollment exceedingly challenging, despite our efforts to accelerate enrollment by expanding the number of participating investigational sites as well as modifying the study protocol to make study inclusion criteria more flexible. Consequently, we have halted enrollment in the study to alleviate the operational and financial burden due to enrollment delays and the lack of visibility on the time to completion. We will consider additional protocol and/or executional changes based on the results of the interim analysis, which are expected in August 2022.”

For more information on this study, please visit clinicaltrials.gov (identifier: NCT04614467).

You May Also Be Interested In

• AstraZeneca (AZN) Announces Voydeya Approval in EU as add-on to ravulizumab or eculizumab
• Neurocrine Biosciences (NBIX) Reports Positive Phase 2 Data for NBI-1065845
• Day One Biopharmaceuticals' (DAWN) OJEMDA receives FDA approval.