FDA Requests Rat PK Data Before DiaMedica’s DM199 IND in Preeclampsia

DiaMedica Therapeutics has received written feedback from the U.S. Food and Drug Administration (FDA) outlining additional nonclinical requirements for the development of DM199 (rinvecalinase alfa) in preeclampsia. The agency indicated that a previously completed rat reproductive toxicity study could support a future U.S. Investigational New Drug (IND) application if the company demonstrates sufficient drug exposure, enzymatic activity, and pharmacologic effects throughout the study.

The feedback provides a potential path forward for DM199, an investigational recombinant human tissue kallikrein-1 (rhKLK1) therapy being developed for preeclampsia, fetal growth restriction, and acute ischemic stroke. Preeclampsia remains a major cause of maternal and fetal morbidity worldwide, with limited treatment options beyond blood pressure management and early delivery.

Why DM199 Matters in Preeclampsia

DM199 is a recombinant form of human tissue kallikrein-1, a naturally occurring serine protease involved in vascular regulation. The enzyme promotes the production of nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor, signaling molecules that help maintain blood vessel function and blood flow.

Researchers believe restoring kallikrein activity may address key biological pathways involved in preeclampsia, a pregnancy-related hypertensive disorder characterized by endothelial dysfunction, impaired placental perfusion, and systemic inflammation. By improving vascular health and blood flow, DM199 could offer a novel therapeutic approach for a condition with substantial unmet medical need.

FDA Feedback and Next Development Steps

To address the FDA’s request, DiaMedica will initiate a dedicated rat pharmacokinetic (PK) study to evaluate DM199 exposure levels and confirm biological activity in the species used for prior reproductive toxicity testing. The company is also compiling data from recently completed studies that support the pharmacodynamic effects of DM199 in rats.

The FDA’s response suggests that generating evidence of adequate systemic exposure and pharmacologic activity could validate rats as an appropriate toxicology model, potentially eliminating the need for additional reproductive toxicity studies.

Once the PK study is completed, DiaMedica plans to submit the new findings and supporting analyses to the FDA for further review as part of its U.S. IND strategy.

Management Perspective

Dr. Julie Krop, Chief Medical Officer of DiaMedica, said the company appreciates the FDA’s guidance and intends to complete the requested nonclinical work while advancing international clinical development efforts.

The feedback appears to narrow the regulatory focus to confirming exposure and biological activity rather than requiring entirely new reproductive toxicology programs, which could streamline the path toward a U.S. clinical study.

Development Outlook

DiaMedica expects to continue generating the nonclinical evidence needed to support a U.S. IND submission for DM199 in preeclampsia. In parallel, the company plans to initiate preeclampsia studies in Canada and the United Kingdom later this year.

The upcoming PK and pharmacologic activity data will be an important regulatory milestone, helping determine whether DM199 can advance into U.S. clinical evaluation as a potential therapy for a serious pregnancy complication that currently lacks targeted pharmacologic treatments.

What This Means for Patients

Preeclampsia is one of the leading causes of serious pregnancy complications, and treatment options remain limited. DM199 is being developed to address the underlying vascular dysfunction associated with the disease rather than simply controlling symptoms. While the therapy is still in development, the FDA’s feedback provides a clearer path for advancing clinical studies. If future trials confirm its safety and effectiveness, DM199 could offer a new treatment option for women with preeclampsia and potentially improve outcomes for both mothers and babies.

Reference

DiaMedica Receives FDA Feedback on DM199 Preeclampsia Nonclinical Program:: DiaMedica Therapeutics, Inc. (DMAC)