Supply chain challenges upend Caladrius' coronary artery disease trial

As Caladrius Biosciences merges with Cend Therapeutics to become Lisata Therapeutics, it’s leaving a coronary artery disease trial by the wayside.

The biotech announced plans to shelve, at least for now, a phase 2b study of Xowna, a cell therapy for coronary microvascular dysfunction, or CMD. The condition is a nonobstructive coronary artery disease that leads to decreased blood flow to the heart muscle.

Enrollment has been paused in the FREEDOM trial while the company conducts an interim analysis from the first 20 patients who completed six months of follow-up. Caladrius said this analysis will determine the efficacy and safety of Xowna and inform “the magnitude of the Xowna effect size” on the endpoints that the FDA will need for a future pivotal study. The company will continue to follow all dosed patients.

“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,” said David Mazzo, Ph.D., Caladrius’ president and CEO.

The analysis is expected to be completed in August, at which point Caladrius will consider next steps for the program. Plans will be detailed before the end of the year.

With FREEDOM, Caladrius set out to corroborate earlier results from a phase 2a study called ESCaPE-CM, which served as a proof-of-concept trial. The company wanted to interrogate the possible effect size for the therapy and better match the patient population to the intended commercial population.

Xowna is a cell therapy that uses the patients’ blood-vessel-forming cells to try to heal damage in the heart muscle. The med is intended for patients with CMD who experience chronic chest pain due to impaired blood flow to the heart.

The company dosed its first patient in FREEDOM in January 2021 only to have COVID-19 supply chain challenges disrupt operations. Caladrius said shortages of catheters, which are used to diagnose CMD, and a contrast agent used by laboratories have slowed enrollment. The manufacturer of the diagnostics selected for the trial discontinued the equipment, leading to a struggle to find replacements amid an already challenging supply chain.

Caladrius made a number of protocol amendments including upping the number of sites to try to circumvent the challenges, but enrollment has still progressed slower than expected. Only one-third of the expected population of 105 patients has been enrolled so far, meaning the trial would have taken about four years to have the data to reach its primary endpoint.

That just wouldn’t be feasible, so Caladrius made the decision to pause.

The company said new techniques have been developed to diagnose CMD, but they continue to not be widely available. The available tests are invasive, requiring coronary angiography or the placement of a catheter directly in the blood vessel. MRI and PET imaging can also be used in some situations.

In April, Caladrius announced plans for a merger of equals with Cend, which will see the two companies become Lisata Therapeutics. The all-stock transaction is expected to close in the third quarter. Mazzo will lead the new company as CEO.

Cend’s solid tumor med CEND-1, which is in phase 1 and 2 trials, was selected as the lead candidate to advance under the newly combined entity.