DiaMedica Therapeutics thinks it has the data to get out from under a stubborn FDA clinical hold. Ten months after its phase 2/3 stroke clinical trial suffered the setback, the biotech is on the cusp of submitting evidence designed to explain the unexpected low blood pressure events and allay concerns.
The FDA imposed the clinical hold in July 2022 in response to three serious adverse event reports related to clinically significant, transient low blood pressure that occurred shortly after initiation of the intravenous dose of DM199. DiaMedica sees the molecule, a recombinant form of human tissue kallikrein-1, as a way to improve stroke recovery, but the clinical hold has held up its push to validate the hypothesis.
Now, the biotech can see the end of its troubles. Management expects to submit a response to the FDA’s clinical hold and ask for the restrictions on the study to be lifted this week. DiaMedica outlined its case for resolving the situation in its first-quarter business update Tuesday.
The problem, as DiaMedica identified in July, appears to stem from a change in the IV bags. Supply issues forced the switch and seemingly changed drug absorption in the bags. Responding to the FDA’s request for additional data, DiaMedica simulated actual use of DM199 in a hospital setting and studied worst-case scenarios by altering variables such as storage duration, temperature and light exposure.
According to DiaMedica, the studies confirm the conclusion that the dose administered in the phase 2b trial was higher than planned, because of the change in IV bag, and caused the low blood pressure. Based on that conclusion, the biotech has proposed lowering the dose from 1.0 µg/kg to 0.5 µg/kg to minimize the blood pressure risk while still providing a therapeutic dose.
The proposals have no effect on the three weeks of subcutaneous dosing required under the protocol, and DiaMedica sees no need to impose special handling restrictions on the investigational product. Once DiaMedica submits the evidence, it will then face a wait to learn what the FDA makes of the proposals.