DiaMedica Therapeutics Inc. announced positive interim results from Part 1a of its Phase 2 study evaluating DM199 (rinvecalinase alfa) for preeclampsia treatment, demonstrating statistically significant blood pressure reductions and a favorable safety profile. The recombinant form of the KLK1 protein achieved pre-specified safety and efficacy endpoints, reinforcing its therapeutic potential in a condition with no approved pharmacological treatments in the United States and Europe.
Dose-Dependent Blood Pressure Reductions
The study revealed substantial dose-dependent reductions in both systolic and diastolic blood pressure. Cohort 9, receiving the highest dose (n=3), achieved the most significant mean reductions at 5 minutes post-infusion: systolic blood pressure decreased by 35 mmHg (p<0.05) and diastolic blood pressure by 15 mmHg (p<0.05).
Pooled cohorts 6-9 (n=12), representing the potentially therapeutic dose range, exhibited statistically significant mean blood pressure reductions at multiple time points, demonstrating durability of response. At 5 minutes, 30 minutes, and 24 hours post-infusion, systolic blood pressure reductions were 25 mmHg (p=0.0003), 15 mmHg (p=0.0018), and 20 mmHg (p=0.0031), respectively. Diastolic blood pressure reductions were 13 mmHg (p=0.0007), 13 mmHg (p=0.0002), and 10 mmHg (p=0.0294) at the same time points.
Safety Profile and Placental Transfer
DM199 demonstrated no placental transfer, addressing a historically significant safety hurdle in preeclampsia treatment development. No serious treatment emergent adverse events were reported across all cohorts. Mild adverse events included nausea in 14% of patients (n=4), headache in 11% (n=3), and flushing in 4% (n=1). No participants discontinued treatment or experienced induction of early labor.
"DM199 could potentially offer a significant safety advantage for both mothers and their babies," said Rick Pauls, President and CEO of DiaMedica Therapeutics, highlighting the importance of the drug not crossing the placental barrier.
Improved Placental Perfusion
DM199 produced a statistically significant 13.2% (p=0.0003) mean reduction in uterine artery pulsatility index at the 2-hour mark, indicating reduced blood flow resistance and improved placental perfusion. This improvement may reduce placental hypoxia, supporting fetal growth and potential disease modification.
Study Design and Patient Population
The investigator-sponsored, open-label, single-center, single-arm study is being conducted at Tygerberg Hospital, Cape Town, South Africa, under the direction of Catherine Cluver, MD, PhD, Professor of Maternal/Fetal Medicine at Stellenbosch University. The trial plans to enroll up to 90 women with preeclampsia and 30 women with fetal growth restriction.
Study participants averaged 32.5 years old with a mean gestation of 37 weeks at enrollment. Baseline measurements showed mean systolic blood pressure of 165 mmHg and mean diastolic blood pressure of 102 mmHg. Following enrollment, participants received DM199 IV infusion, with blood pressure measurements at 5 and 30 minutes post-infusion. For cohorts 2-9, participants received subcutaneous injection at 1 hour post-IV, with measurements continuing through 24 hours.
Approximately 80% of deliveries occurred within 24 hours following enrollment, with 9 vaginal deliveries and 16 cesarean sections recorded.
Clinical Significance and Next Steps
"With hypertension being the leading cause of delivery, often prematurely, in early onset preeclampsia, DM199's ability to safely reduce blood pressure represents an exciting development in the search for an effective treatment for preeclampsia," said Professor Cathy Cluver, principal investigator and leader of the Preeclampsia Research Unit at Tygerberg Hospital.
Based on the positive results, the company will proceed with enrollment of the dose expansion cohort (Part 1b). Additionally, enrollment in the fetal growth restriction cohort (Part 3) will be initiated based on the observed pulsatility index reductions.
Preeclampsia affects up to 8% of pregnancies worldwide and poses significant risks including stroke, placental abruption, progression to eclampsia, premature delivery, and death. The condition occurs when the placenta fails to embed properly in early pregnancy, leading to chronic oxygen starvation and subsequent release of noxious factors that cause systemic endothelial dysfunction after 20 weeks of pregnancy.
