Guard Therapeutics' RMC-035 Fails Phase 2b POINTER Trial Despite Earlier Positive Results
核心洞察
Guard Therapeutics (搜索) announced that its Phase 2b POINTER study of RMC-035 for kidney protection during open-heart surgery failed to meet primary and key secondary efficacy endpoints.
The study showed no statistically significant difference between RMC-035 and placebo in estimated glomerular filtration rate (搜索) change from baseline to Day 90, with a placebo-adjusted change of −2.76 mL/min/1.73 m² (p=0.17).
These disappointing results contrast sharply with earlier positive Phase 2a AKITA study data that demonstrated robust kidney function improvements and favorable biomarker profiles.
Guard Therapeutics (搜索) announced disappointing top-line results from its Phase 2b POINTER study, revealing that the investigational drug candidate RMC-035 failed to demonstrate kidney-protective benefits in patients undergoing open-heart surgery. The study did not meet its primary and key secondary efficacy endpoints, marking a significant setback for the company's lead therapeutic program.
Primary Endpoint Results Fall Short
The Phase 2b POINTER study failed to demonstrate a statistically significant difference between RMC-035 and placebo in the primary endpoint of change in estimated glomerular filtration rate (搜索) (eGFR) from baseline to Day 90. The placebo-adjusted change in eGFR for RMC-035 at Day 90 was −2.76 mL/min/1.73 m² with a 90% Confidence Interval of −6.10 to 0.58 and p-value of 0.17.
The key secondary endpoint, Major Adverse Kidney Events at Day 90 (MAKE90), also failed to reach statistical significance. The common relative risk for MAKE90 was 0.89 with a 90% CI of 0.48 to 1.66 and p-value of 0.76.
"The results from the POINTER study are disappointing, given previous findings of efficacy for RMC-035 and the significant unmet medical need in preventing irreversible kidney damage after open-heart surgery," said Tobias Agervald, CEO of Guard Therapeutics (搜索).
Safety Profile Remains Favorable
Despite the efficacy disappointment, RMC-035 maintained its favorable safety profile. The drug was generally well tolerated throughout the study, and no safety concerns were identified during the trial period.
Contrast with Earlier Positive Results
The POINTER study results stand in stark contrast to the company's earlier Phase 2a AKITA study, which demonstrated robust improvements in kidney function following open-heart surgery. In October 2025, Guard Therapeutics (搜索) had announced additional positive analyses from the AKITA study showing that RMC-035 provided kidney-protective benefits in both patients with and without acute kidney injury (搜索).
The AKITA study had shown statistically significant improvements in kidney function measured by eGFR, with a net difference of 5.5 mL/min/1.73 m² (90% CI 1.7–9.4; P = 0.019) among patients without acute kidney injury (搜索) and 4.9 mL/min/1.73 m² (90% CI 0.8–9.1; P = 0.056) among patients with acute kidney injury at Day 90.
The earlier study also demonstrated favorable effects on important biomarkers, including a significant reduction in albuminuria (搜索) in patients with chronic kidney disease (搜索) and attenuation of Kidney Injury Molecule-1 (搜索) (KIM-1) increases at 24 hours post-surgery.
Strategic Evaluation Ahead
The complete data set from POINTER is expected to be available within approximately two weeks, though the company does not anticipate that additional analyses will change the overall study outcome. Guard Therapeutics (搜索) hosted a web conference on October 27 to discuss the study results and respond to questions from stakeholders.
Upon completion of the full data review, the company's Board of Directors will initiate a strategic evaluation process to determine the optimal path forward. This comprehensive review will include an assessment of the company's remaining resources, an integrated analysis of the full RMC-035 data set and the GTX peptide technology platform, as well as potential strategic alternatives.
"While the data do not support further development of RMC-035, we remain committed to fully understanding the study outcome and evaluating next steps," Agervald stated. The company indicated that further communication will be provided once the strategic evaluation process has been completed.