Recursion's REC-994 Shows Promising Safety and Efficacy Signals in Phase 2 CCM Trial
核心洞察
REC-994 demonstrated a favorable safety profile in the Phase 2 SYCAMORE (搜索) trial for Cerebral Cavernous Malformations (搜索), with no treatment-related discontinuations or serious adverse events.
The 400mg dose showed encouraging efficacy signals, with 50% of patients experiencing lesion volume reduction and improved functional outcomes compared to placebo after 12 months of treatment.
Particularly notable benefits were observed in patients with brainstem lesions, representing a significant advancement for this high-unmet-need population where surgical intervention is not possible.
Recursion (Nasdaq: RXRX) has announced positive 12-month data from its Phase 2 SYCAMORE (搜索) trial of REC-994, marking a significant milestone as the first industry-sponsored Phase 2 trial completed in Cerebral Cavernous Malformations (搜索) (CCM). The results were presented at the International Stroke Conference in Los Angeles, highlighting promising therapeutic potential for CCM patients.
Safety Profile Meets Primary Endpoint
The trial successfully met its primary endpoint of safety and tolerability. No significant safety signals were observed, with adverse events comparable between treatment and placebo arms. The most common side effects, reported in at least 10% of participants, included COVID-19, dizziness, headache, back pain, and constipation. Importantly, there were no treatment-related serious adverse events or discontinuations, with most treatment-emergent adverse events being Grade 1-2.
Efficacy Signals Show Promise
The 400mg dose of REC-994 demonstrated encouraging efficacy signals across multiple measures. Half of the patients receiving this dose (N=20) showed reduction in total lesion volume, compared to 28% in the placebo group (N=18). The absolute mean decrease in total lesion volume was -457 mm³ in the 400mg arm, contrasting with mean increases of 61 mm³ and 53 mm³ in the 200mg and placebo arms, respectively.
Functional Outcomes and Brainstem Lesions
Dr. Jan-Karl Burkhardt, Division Head of Cerebrovascular Surgery at the University of Pennsylvania and Principal Investigator, noted, "The results demonstrate safety of REC-994 for CCM patients and promising trends of efficacy including 50% of patients achieving a reduction in mean lesion volume after 12 months of treatment and improved functional outcome as assessed by mRS at the 400mg dose."
Particularly encouraging results were observed in patients with brainstem lesions, a subset with significant unmet medical needs due to the impossibility of surgical intervention. These patients showed similar trends in lesion volume reduction and functional improvement or stabilization with the 400mg dose.
Modified Rankin Scale Improvements
The modified Rankin Scale (mRS), an FDA-recognized measure of functional outcomes in stroke trials, showed promising trends. Despite starting with worse clinical function (higher proportion of mRS scores ≥3), patients on 400mg REC-994 demonstrated trends toward improvement or stabilization of symptoms, while the placebo group showed tendencies toward functional decline.
Additional Findings and Future Direction
The study revealed time-dependent reductions in hemosiderin ring size in the 400mg arm compared to lower dose and placebo groups. While seizure frequency appeared reduced in the 400mg arm, baseline imbalances in seizure history across groups warrant careful interpretation.
Najat Khan, Ph.D., Chief R&D Officer and Chief Commercial Officer of Recursion, stated, "These preliminary results show promising MRI-based and functional outcome signals, and we look forward to continued discussions with the FDA, and the CCM scientific and patient communities on next steps."
The company plans to submit these findings for peer-reviewed publication, with future steps to be guided by regulatory discussions and ongoing long-term extension study results.