DiaMedica Therapeutics’ ReMEDy2 trial remains on clinical hold, with the FDA requesting more data to allay its concerns about how the potential stroke drug is administered intravenously.
The agency placed the hold on the phase 2/3 trial of DiaMedica's only clinical asset, called DM199, back in July in response to three adverse events of transient acute hypotension, or low blood pressure, when the drug was infused intravenously.
DiaMedica already handed the FDA in vitro data suggesting the blame for the adverse events is likely to lie with the type of IV bag used. The bag was different to that used in the ReMEDy1 trial, when no hypotensive episodes were reported, the company noted in a release yesterday.
Hypotension is a known response to DM199 treatment, DiaMedica said in the release. The candidate is a synthetic version of a protein called human tissue kallikrein-1, which was being studied for acute ischemic stroke. Significant differences in protein binding were observed between the types of IV bags used in the two studies, which the company believes altered the total amount of drug being administered.
After reviewing the data, the FDA has requested an additional study of the IV infusion process and equipment to rule out this cause. DiaMedia has already begun preparing this study and will request a meeting with the agency to confirm the study’s design as well as receive guidance on a path toward lifting the trial hold.
The ReMEDy2 trial, which, according to ClinicalTrials.gov launched in September 2021, was designed to enroll 350 patients across 75 sites in the U.S. The company had voluntarily paused the trial after the three unexpected cases of clinically significant hypotension were reported. The effect was transient, and the blood pressure of all three patients recovered within minutes of stopping the infusion, with no ongoing adverse effects, DiaMedica noted.
The company is understandably keen for the hold to be lifted, having tried to conserve capital while the FDA makes a decision. DiaMedica had cash, equivalents and marketable securities totaling $36.1 million as of Sept. 30.
Aside from stroke, DiaMedica is also studying DM199 in phase 2 trials for IgA nephropathy and in African Americans with chronic kidney disease. The only other asset in the company’s pipeline is a preclinical recombinant protein called DM300.