New Treatment Could End the Phlebotomy Cycle for Men with High Hematocrit
If you're a man on testosterone replacement therapy (TRT) who's been told you need regular blood draws to manage your hematocrit levels, a breakthrough treatment currently in clinical trials could change everything. Recent research on a drug called rusfertide shows promise for maintaining healthy hematocrit levels without the constant need for therapeutic phlebotomies.The Problem You Know Too Well
Men on TRT frequently develop elevated hematocrit—a condition where your blood becomes too thick due to an overproduction of red blood cells. When your hematocrit rises above 54% (some doctors use 52%), you're at increased risk for blood clots, stroke, and heart problems. The standard solution? Regular therapeutic phlebotomies, essentially controlled blood donations to thin your blood.But here's the frustrating reality: this approach often feels like you're on a hamster wheel. You get a phlebotomy, your hematocrit drops, but then it climbs back up again, requiring another blood draw in a few weeks or months. It's reactive medicine at its finest—treating the symptom without addressing the underlying cause.
A Different Approach: Targeting the Root Cause
Researchers studying polycythemia vera (a blood disorder that causes similar hematocrit problems) have developed rusfertide, a synthetic version of hepcidin—a hormone your liver naturally produces to regulate iron absorption. Instead of repeatedly removing blood, this treatment works by controlling how much iron your body absorbs and uses to make red blood cells.Think of it this way: if your body is a factory producing too many red blood cells, traditional phlebotomy is like periodically emptying the warehouse. Rusfertide, on the other hand, reduces the raw materials (iron) going into the factory, naturally slowing production to normal levels.
The Clinical Results Are Impressive
In the REVIVE Phase 2 study, 69.2% of patients maintained healthy hematocrit levels below 45% without needing any phlebotomies during a 12-week period. Even more striking, 92.3% of patients in the treatment group avoided phlebotomy entirely during this phase.For context, maintaining hematocrit below 45% is crucial because studies show this significantly reduces the risk of blood clots and cardiovascular events—the very complications that make managing high hematocrit so important.
The Reality of Drug Approval
It's important to understand that rusfertide will likely receive orphan drug status specifically for polycythemia vera, not for polycythemia caused by testosterone replacement therapy. This means the FDA approval process and initial marketing will focus exclusively on this rare blood disorder, which affects approximately 100,000-150,000 patients in the United States. Men experiencing elevated hematocrit from TRT would be considered an "off-label" use, meaning doctors could potentially prescribe it, but insurance coverage would be uncertain and the drug company won't be able to market it specifically for TRT-related polycythemia. This regulatory pathway could significantly impact both availability and cost for TRT patients, even though the underlying mechanism—excess red blood cell production—is essentially identical.What This Could Mean for TRT Patients
While this study focused on polycythemia vera patients, the mechanism is directly relevant to men on TRT experiencing elevated hematocrit. Both conditions involve the same fundamental problem: too many red blood cells leading to dangerously thick blood.Current standard care for TRT-related high hematocrit often means:
- Regular blood draws every 6-12 weeks
- Scheduling challenges and time off work
- Potential iron deficiency from repeated phlebotomies
- The constant worry about when your next blood test will show rising levels
- Stable hematocrit levels without regular phlebotomies
- Better quality of life and symptom management
- Reduced anxiety about cardiovascular risks
- More consistent energy levels
Important Considerations
The drug was generally well-tolerated in trials, with most side effects being mild skin reactions. However, it's worth noting that the FDA temporarily placed a hold on the trial due to concerns from animal studies, though this was later resolved and the study continued.The treatment is currently being tested in a Phase 3 trial, which means it's still several years away from potential FDA approval and availability to the general public.
The Bottom Line
For men dealing with TRT-related high hematocrit, rusfertide represents a potentially game-changing approach. Instead of the endless cycle of phlebotomies that treat the symptom, this treatment addresses the underlying mechanism causing red blood cell overproduction.While we wait for more definitive results and eventual FDA approval, this research offers hope for a future where managing hematocrit doesn't mean being tethered to regular blood draws. It's a reminder that sometimes the best solutions come not from doing more of the same, but from fundamentally rethinking the problem.
If you're currently managing high hematocrit with regular phlebotomies, this is definitely worth discussing with your doctor as the research progresses. The prospect of maintaining healthy levels through a targeted treatment rather than reactive blood removal could represent a major quality-of-life improvement for thousands of men on TRT.
Note: This information is for educational purposes only. Always consult with your healthcare provider about your specific situation and treatment options.
*rusfertide, a novel hepcidin mimetic
Elevated hematocrit is a hallmark of polycythemia vera (PV), and it is associated with higher rates of death. Whilst it is essential to maintain hematocrit levels below 45% to decrease the risk of thrombotic and cardiovascular events, current standards of care (SOC) are not effective in the majority of patients. In this presentation, Ronald Hoffman, MD, presents results from the REVIVE study (NCT04057040), which evaluated the efficacy of rusfertide, a novel hepcidin mimetic, in patients with PV. The study met its primary endpoint of maintaining hematocrit levels below 45% and demonstrated that rusfertide was highly efficacious in controlling erythrocytosis. The data from the randomized withdrawal phase demonstrated the superior efficacy of rusfertide in eliminating the need for additional therapeutic phlebotomies as compared to placebo. Rusfertide therapy was associated with persistent hematocrit (HCT) control and improvements in PV-related symptoms. The treatment was generally well tolerated. The positive outcomes of the REVIVE study showcase the efficacy and tolerability of rusfertide as a highly effective therapy for uncontrolled erythrocytosis and associated symptoms in PV and is currently being investigated in the ongoing Phase III VERIFY study (NCT05210790). This press briefing took place at the European Hematology Association (EHA) Congress 2023, held in Frankfurt, Germany.
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