DiaMedica Therapeutics’ Phase II/III ReMEDy2 trial is on hold by the FDA because patients were experiencing severe drops in blood pressure.
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DiaMedica Therapeutics’ Phase II/III ReMEDy2 trial is on hold. The study, which is testing DM199 to treat acute ischemic stroke (AIS) patients, was stopped by the U.S. Food and Drug Administration because patients were experiencing severe drops in blood pressure. The hold is the latest obstacle encountered in this trial.
“Patient safety is very important as we plan and conduct our clinical studies,” Kirsten Gruis, M.D., chief medical officer of DiaMedica said. “Patient blood pressure is easily and routinely monitored in stroke patients which is why our study sites were able to quickly identify the issue and immediately stop the dosing of DM199, after which the patients then recovered within minutes and suffered no injuries. We are committed to working diligently with the FDA to resolve this issue and resume the trial as soon as reasonably practicable.”
DM199 is a recombinant form of human tissue kallikrein-1 (KLK1). When the body does not have enough KLK1, the deficiency can lead to disruption of various physiological processes and may play a role in strokes, chronic kidney disease, retinopathy, vascular dementia and resistant hypertension.
The drug is the first pharmaceutically active recombinant (synthetic) form of KLK1 to ever be made. The FDA granted it Fast Track designation in September 2021 to treat AIS patients.
The ReMEDy2 trial is intended to enroll about 350 patients at more than 75 sites across the United States. Participants in the trial receive either treatment with DM199 or a placebo within 24 hours of experiencing symptoms of a stroke. After 90 days, a follow-up helps determine how the patient is doing.
The trial has two primary endpoints. The first one is recovery from stroke based on the modified Rankin Scale (mRS). Because 25% of ischemic strokes are recurrent, the second endpoint is stroke recurrence within the 90-day follow-up.
However, the program is facing challenges. DiaMedica submitted three serious adverse event reports to the FDA related to clinically significant, transient hypotension (low blood pressure) occurring shortly after initiation of the intravenous dose of DM199. The company paused patient enrollment and the FDA has placed a clinical hold on the trial.
The cause of the low blood pressure may not be a problem with the drug itself. In a press release, DiaMedica stated that it suspects the IV bags used to administer the drug may be the cause of the adverse events.
In the ReMeDy1 trial, no blood pressure issues were reported in any of the 46 patients. However, the type of IV bag used in that trial is not available in many hospitals due to supply chain issues. After some compatibility testing, DiaMedica chose to use a different type of bag. As the company retraced its steps, testing revealed that the new bags had differences in drug absorption.
In order for the FDA to allow the trial to continue, DiaMedica must provide an analysis of what happened, suggested protocol to correct the problem in the future and data to support the protocol suggestions.
DiaMedica is already planning tp submit a revised ReMEDy2 trial protocol with the supporting rationale and data to the FDA for review as soon as it finishes its compatibility analysis.
The hold is another blow to the clinical trial. In DiaMedica’s Q1 2022 business update, the company acknowledged the trial was experiencing slower than expected site activations and enrollment due to staff shortages, the COVID-19 pandemic and site management logistics. The trial had planned to operate in 75 sites, but up until the FDA hold, DiaMedica had activated just nine.
The company remains optimistic, though.
“While having to pause enrollment in the ReMEDy2 trial was not desirable, we remain confident about the future potential of DM199 and are committed to refining the dosing procedures and methods that will further enhance patient safety,” Rick Pauls, DiaMedica’s president and CEO said.
