Development

Cadrenal's CAD-1005 advances to Phase III trial for heparin-induced thrombocytopenia treatment

Cadrenal Therapeutics (Nasdaq: CVKD) announced that it has completed an End-of-Phase II meeting with the FDA for CAD-1005, its investigational 12-lipoxygenase inhibitor for heparin-induced thrombocytopenia, clearing a path to a pivotal Phase III trial after Phase II data showed a greater than 25% absolute reduction in thrombotic events when the drug was added to standard anticoagulant therapy.

The planned pivotal study is a randomized, blinded, placebo-controlled trial enrolling approximately 120 patients with suspected HIT across up to 50 clinical centers worldwide, with a primary endpoint of new or worsening thrombotic events in patients with Serotonin Release Assay-confirmed HIT. Cadrenal projects an NDA submission in 2029.

Phase II data showed that CAD-1005, added to standard-of-care anticoagulation, produced a greater than 25% absolute reduction in thrombotic events compared with anticoagulation alone. The press release does not disclose the full Phase II patient numbers, statistical confidence intervals, or secondary endpoint detail, so the magnitude and precision of that signal cannot be independently assessed from available data. No improvement in platelet count recovery was reported.

CAD-1005 (formerly VLX-1005) inhibits 12-LOX, an enzyme implicated in the immune-mediated platelet activation cascade that underlies HIT. That mechanism distinguishes it from the two agents currently available for HIT in the US — argatroban, a direct thrombin inhibitor approved by the FDA in 2000, and bivalirudin (Angiomax [bivalirudin]), whose FDA label covers HIT patients undergoing percutaneous coronary intervention. Both approved agents act downstream, blunting thrombin generation rather than interrupting the upstream antibody-driven platelet activation that initiates the condition. CAD-1005 is designed as an adjunct to anticoagulation rather than a replacement, positioning it to address the residual thrombotic risk that persists even with optimal anticoagulant management.

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The HIT treatment landscape has been static for more than two decades. No new molecular entity has received FDA approval for this indication since argatroban in 2000, a gap that reflects both the complexity of the disease biology and the challenges of conducting controlled trials in an acute, heterogeneous population. HIT occurs in a subset of the more than 12 million patients who receive heparin annually in US hospitals, when antibodies directed against platelet factor 4-heparin complexes activate platelets and trigger systemic thrombosis. Mortality rates exceed 20% in some published series, and complications include deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, and amputation.

CAD-1005 holds Orphan Drug Designation and Fast Track designation from the FDA, as well as orphan drug status from the European Medicines Agency. Those designations do not guarantee approval but do provide procedural advantages, including eligibility for priority review and potential for more frequent FDA interaction during development.


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