In response to up to date findings from the section 3 VERIFY examine offered on the 2025 ASH Annual Assembly, remedy with the hepcidin mimetic rusfertide continued to exhibit sustained hematocrit management under 45% and excessive charges of phlebotomy ineligibility by week 52 for sufferers with polycythemia vera (PV).
For many who crossed over from placebo to rusfertide, there was a speedy and sturdy drop of their hematocrit ranges inside the first 4 weeks. Each teams had comparable ranges of hematocrit management by week 52, no matter having acquired placebo or rusfertide within the first a part of the examine. For these persevering with rusfertide from half 1a of the examine to half 1b, the response price, outlined as absence of phlebotomy eligibility, went from 76.9% to 84.1%. For many who switched from placebo partially 1a to rusfertide partially 1b, the response went from 32.9% to 77.9%.
“Rusfertide met the first and all 4 secondary finish factors in VERIFY from baseline to week 32 and continued to offer sturdy, sustained management of hematocrit under 45% and phlebotomy ineligibility by week 52,” lead investigator Dr. Andrew Kuykendall, at Moffitt Most cancers Middle within the Division of Malignant Hematology, stated throughout a presentation of the outcomes. “After 52 weeks of remedy in VERIFY, rusfertide was nicely tolerated with a security profile that was in line with prior observations.”
What’s the examine design of VERIFY?
The section 3 examine was damaged into a number of elements. Partially 1a, sufferers have been randomly chosen to obtain the present normal of care plus rusfertide (147 sufferers) or placebo (146 sufferers) for 32 weeks, with main finish factors assessed at weeks 20 to 32. After this preliminary interval, sufferers within the placebo group crossed over to obtain rusfertide plus normal of care. This open-label a part of the examine (half 1b; 274 sufferers) continued till week 52 at which level sturdiness of response was assessed. Commonplace of care was outlined as phlebotomy with or with out cytoreductive remedy. Subsequent elements of the examine are ongoing to evaluate long-term security. Outcomes from ASH have been for Half 1b.
Baseline traits have been balanced between teams partially 1a of the examine, Kuykendall famous. Partially 1b, the median age was 57 years, and most sufferers have been male (72.6%). Practically half of sufferers had high-risk PV (44.9%), which was outlined as having a previous thromboembolic occasion and/or age 60 or older. The median age at PV analysis was 51 years and the median PV length was 2.9 years.
Practically half of sufferers weren’t on a cytoreductive remedy for half 1b of the examine (44.9%), which was in line with half 1a. For these on remedy, the most typical was hydroxyurea (38.3%) adopted by interferons (13.9%). There was a small subset of sufferers on ruxolitinib (2.6%; Jakafi).
What have been the outcomes from half 1a of the VERIFY examine?
Partially 1a of the examine, rusfertide was superior to placebo throughout all key finish factors. For placebo and rusfertide, respectively, the response charges have been greater than doubled (32.9% vs 76.9%) and 62.6% of these on rusfertide had a hematocrit decrease than 45% in contrast with 14.4% for placebo. There have been fewer imply phlebotomies required with rusfertide (0.5 sufferers) in contrast with placebo (1.8 sufferers).
Along with scientific finish factors, patient-reported outcomes have been additionally superior with rusfertide. For the PROMIS fatigue SF-8a T-score, there as a 0.17 improve at week 32 with placebo in contrast with a decline of 1.78 for rusfertide, suggesting much less fatigue (-1.95 delta). Enchancment was additionally seen in Myelofibrosis Symptom Evaluation Type Model 4.0 Whole Symptom Rating 7 Objects, with a 0.54 drop with placebo and a 2.4 drop for rusfertide (-1.87 delta).
What have been the brand new rusfertide findings from half 1b of VERIFY?
The median time to phlebotomy was not reached within the rusfertide arm in contrast with 16 weeks within the placebo group for half 1a. Partially 1b, the median time to phlebotomy was not estimable in each arms. “As soon as sufferers switched from placebo to rusfertide, time to first phlebotomy appeared comparable in each teams,” Kuykendall stated.
Ferritin ranges normalized over time for these receiving rusfertide, with a continued enchancment seen with rusfertide all through the course of the examine. There was no change with placebo partially 1a however a constant climb in ferritin as soon as sufferers crossed over to acquired rusfertide. There was solely a small change in serum iron ranges in each teams of sufferers (from ~6 µm ol/L at baseline growing to ~10 µm ol/L). Transferrin ranges decreased with rusfertide whereas transferrin saturation elevated. As with all ranges, a major shift might be seen with sufferers moved from placebo to rusfertide.
“Rusfertide lowered hematocrit ranges with out exacerbating systemic iron deficiency,” added Kuykendall.
There was a modest enchancment in imply corpuscular quantity ranges with rusfertide. Leukocytes counts have been steady in each arms with a slight improve, and an enchancment in platelet counts was seen with rusfertide.
What was the security profile for rusfertide in VERIFY?
On the information cutoff, 86.7% of sufferers continued to obtain open-label rusfertide, with discontinuations being unusual, Kuykendall stated. Partially 1a, simply 7.5% of sufferers discontinued rusfertide because of negative effects (8 sufferers) or examine withdrawal (3 sufferers). This in contrast with a discontinuation price of 4.1% within the placebo group for negative effects (5 sufferers) and illness development (1 affected person). Partially 1b, the discontinuation price was 2.6%, with three from negative effects, two from lack of efficacy, one for different causes, and one for examine withdrawal.
Partially 1a there have been fewer secondary most cancers occasions within the rusfertide group in contrast with placebo (3 versus 8, respectively). Partially 1b, those that switched from placebo had two most cancers occasions in contrast with 4 within the arm that was on rusfertide for each half 1a and 1b.
Most negative effects have been grade 1 (delicate) or 2 (average) in severity, with a minimum of one treatment-emergent negative effects occurring in 86.3% of these within the placebo group and for 90.3% of these within the rusfertide group partially 1a. Partially 1b, remedy associated negative effects charges have been comparable between teams at roughly 75%. The commonest grade 3 (extreme) remedy associated negative effects have been anemia, asthenia, and hypertension, Kuykendall famous. These occurred in three sufferers every. Critical negative effects have been skilled by 3.4% of sufferers partially 1a and for two.6% partially 1b.
Partially 1a of the examine, injection website reactions occurred in 32.9% of these within the placebo group and in 55.9% within the rusfertide group. Partially 1b, infusion website reactions have been seen in 32.9% of these within the crossover group and for 9.7% within the rusfertide arm.
“Optimistically, you’ll be able to see that among the injection website reactions truly go down within the rusfertide arm from week 32 to 52, suggesting it could reduce over time,” Kuykendall stated.
What are the following steps for rusfertide?
A regulatory submission is being deliberate for rusfertide as a remedy for sufferers with PV. Information for the submission will come from the VERIFY examine together with outcomes from the REVIVE examine. Within the REVIVE examine, the response price with rusfertide was 60% in contrast with 17% for placebo.
Half 2 and three of the VERIFY examine will proceed to evaluate long-term efficacy and security for rusfertide, with half 2 scheduled to go to week 156 and half 3 expending from the tip of half 2 by the tip of remedy.
References
- “Rusfertide or placebo plus present standard-of-care remedy for polycythemia vera: Sturdiness of response and security outcomes by week 52 from the randomized managed section 3 VERIFY examine” by Dr. Kuykendall, et al., Blood
- “Rusfertide, a hepcidin mimetic, for management of erythrocytosis in polycythemia vera” by Dr. Kremyanskaya, et al., New England Journal of Drugs
For extra information on most cancers updates, analysis and schooling, don’t neglect to
