Caladrius Biosciences announced it was suspending enrollment in its Phase IIb FREEDOM study assessing xowna for coronary microvascular dysfunction (CMD) due to supply chain issues.
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Shares of Caladrius Biosciences were falling Tuesday in premarket trading after the company announced it was suspending enrollment in its Phase IIb FREEDOM study assessing xowna for coronary microvascular dysfunction (CMD) due to supply chain issues and the impact of the COVID-19 pandemic.
One of the key issues impacting the FREEDOM trial is that the diagnostic equipment that was originally specified in the trial to qualify patients has been discontinued by the manufacturer, David J. Mazzo, president and chief executive officer of Caladrius, said. Additionally, Mazzo noted that there are shortages of catheters that are qualified for the administration of xowna, as well as supply shortages of a contrast agent that is commonly employed in many catheter laboratories.
The company noted that there were protocol amendments made to address those obstacles. However, Caladrius saw meager enrollment in the FREEDOM study. As of Monday, the trial had only enrolled approximately one-third of the targeted 105 patients.
“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,” Mazzo said in a statement.
He also noted the availability of new diagnostic technology for CMD, a type of non-obstructive coronary artery disease that causes decreased blood flow to the heart. However, he said these techniques are not widely available nor are the associated diagnostic parameters widely accepted.
Xowna is an experimental, autologous cell therapy that is made from CD34+ cells.
Although the study has been paused, Caladrius said it will conduct an interim analysis of data from the first 20 patients who were enrolled. The company will use the six-month follow-up data to evaluate the efficacy and safety of xowna in subjects with CMD. Once that analysis is made, Caladrius said it will corroborate those results with the ESCaPE-CMD study results.
Data from the Phase IIa ESCaPE-CMD trial showed that patients who were treated with xowna demonstrated a “highly statistically significant improvement” in coronary flow reserve. That correlated with symptom relief for CMD patients following a single intracoronary injection of the experimental cell therapy.
Once these analyses are known, Caladrius said the data is expected to “provide an indication of the magnitude of the xowna effect size” on the safety and efficacy endpoints that will likely be required from the U.S. Food and Drug Administration for potential regulatory approval. The interim analysis of the FREEDOM data is expected to be completed in August.
Mazzo said the decision to pause the study and conduct the analysis is in the company’s best interests. He speculated that this will provide Caladrius with meaningful insight into the best future clinical development pathway of the program.
“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,” he added.
Following the interim analysis, Caladrius said that it will conduct a business review to determine the next steps in the development program of xowna. That is expected to occur before the end of the year.
New Jersey-based Caladrius announced the study pause Monday afternoon and it sparked the stock slide. Shares were down more than 2% in premarket trading to 45 cents.
