Phase IIa IMPRSSION trial: Sapablursen in phlebotomy-dependent PV

Results from the ongoing phase IIa, randomized, open-label IMPRSSION (NCT05143957) study evaluating sapablursen, an antisense oligonucleotide (ASO) targeting transmembrane serine protease 6 (TMPRSS6), added to standard of care (SoC) in 49 patients with phlebotomy-dependent polycythemia vera (PV) were published in Blood by Palmer et al. Phlebotomy dependence was defined as patients who had ≥3 phlebotomies in the preceding 6 months and ≥1 phlebotomy within the last 12 weeks. Patients in Cohort A received sapablursen 120 mg to Week 13, before switching to 80 mg through Week 37. Patients in Cohort B received sapablursen 40 mg throughout. The primary efficacy endpoint was the reduction from baseline in the number of phlebotomies per week between Weeks 17 and 37.

Key data: The estimated mean number of phlebotomies per year was reduced from 7.8 to 2.6 and from 8.8 to 3.6 in Cohorts A and B, respectively. The mean weekly phlebotomy rate was significantly reduced from baseline in both Cohort A (–0.10; 95% confidence interval [CI], –0.13 to –0.07; p < 0.0001) and B (–0.10; 95% CI, –0.14 to –0.06; p = 0.0001). Overall, 53% of patients in Cohort A and 41% of patients in Cohort B had a >90% reduction in phlebotomy rate. Mean hematocrit values were reduced from 46.4% at baseline to 41.5% at Week 17 and 40.5% at Week 37 in Cohort A, and from 45.5% to 42.9% and 43.5%, respectively, in Cohort B. The Myeloproliferative Neoplasm-Symptom Assessment Form Total Symptom Score (MPN-SAF-TSS) significantly improved from baseline to Week 37 in Cohort A (mean change from baseline [CFB], −6.21; p = 0.0052), but not Cohort B (mean CFB, −2.71; p = 0.34). Treatment-emergent adverse events (TEAEs) occurred in 97% of patients in Cohort A and 82% in Cohort B; most TEAEs were mild (75%) or moderate (22%) in severity. Serious adverse events (SAEs) were reported in 18% of patients. 

Key learning: In the IMPRSSION trial, sapablursen significantly reduced phlebotomy requirements and improved symptoms in patients with phlebotomy-dependent PV, supporting 80 mg as an appropriate starting dose. Sapablursen will be further evaluated in the planned placebo-controlled phase III INTREPID study (NCT07429266).