At ASH we presented the results of parts 1a and 1b of the VERIFY study. This is a phase III study assessing the safety and efficacy of rusfertide, a hepcidin memetic, in patients with polycythemia vera.

What was the study design?

The study design was patients who have polycythemia vera who were requiring frequent phlebotomy were enrolled and randomised 1:1 to either go on rusfertide versus placebo in addition to their current standard of care. So everyone received their current standard of care and then were randomised to either rusfertide or placebo in addition to that.

The study was broken into different parts and part 1a, which was 32 weeks, this was the blinded portion of the study.  The first 20 weeks of that 32 weeks was a dose titration phase and the primary endpoint was assessed from weeks 20-32. The primary endpoint was the absence of phlebotomy eligibility and this was compared from rusfertide versus placebo.

After week 32 patients rolled over into part 1b. This was the open label portion of the study, so patients who were initially randomised to rusfertide continued on rusfertide. Those patients who were randomised to placebo rolled over onto rusfertide at that point in time. This was followed by parts 2 and 3 which were not presented at ASH but are ongoing and this is the open label extension and safety assessment period of time.

What were the key results?

Earlier this year at ASCO we presented the primary results from part 1a of the study and in that presentation we showed that rusfertide met its primary and all four key secondary endpoints. The primary endpoint focussed on the absence of phlebotomy eligibility but also the key secondary endpoints looked at other measures of haematocrit control, so the ability to maintain haematocrit at goal less than 45% for weeks 0-32 as well as rusfertide showed the ability to have fewer phlebotomies on average compared to patients who were randomised to placebo.

The second two key secondary endpoints focussed on patient-reported outcomes and there rusfertide showed an improvement in the PROMIS fatigue score compared to those randomised to placebo, as well as an improvement in the myelofibrosis symptom assessment form.

So what we presented earlier was that rusfertide was able to meet its primary and all four key secondary endpoints in terms of controlling haematocrit consistently as well as patient-reported outcomes. At ASH this year we extended upon that and presented the part 1b which was the rollover portion. Here we showed that rusfertide patients who stayed on rusfertide continued to maintain that durable response and were able to actually increase their response rates as you get further on into part 1b. Those patients who were initially randomised to placebo were able to achieve similar response rates when they rolled over onto rusfertide as we saw in part 1a of the study in patients initially randomised to rusfertide.

What is the clinical significance of these results?

The clinical significance is that now we have an agent which hopefully at some point will be approved and will replace our current standard of care in terms of relying upon this kind of archaic phlebotomies or repeated phlebotomies. So patients who are receiving phlebotomies, which is really a standard of care for most patients with polycythemia vera at some point during their treatment course, who are struggling with those, who don’t tolerate those or who don’t really want to be tied to the healthcare system now have an alternative strategy to consistently and safely maintain haematocrit levels at goal. This is something that can be done in patients who are not on cytoreductive therapy or it can be added to their current standard of care, whichever cytoreductive therapy they are currently on.

Additionally, this offers an agent that has shown symptomatic improvement. So we know patients with PV have decreased quality of life so this is something that can have the potential to improve that quality of life as they live with this disease.