Tag Archives: pv

Fatigue, Quality of Life Improve With Rusfertide: Andrew Kuykendall, MD

Posted on by

April 27, 2025

Author(s): Maggie L. Shaw, Andrew Kuykendall, MD

Bringing this interview with Andrew Kuykendall, MD, clinical researcher at Moffitt Cancer Center, to a close, he addresses safety concerns that have been linked to the injectable hepcidin mimetic rusfertide (Takeda) and its overall impact on patient quality of life. Rusfertide is under investigation for treatment of polycythemia vera, a myeloproliferative neoplasm, in the ongoing phase 3 VERIFY trial (NCT05210790), on which Kuykendall is an investigator.

Previous segments of this interview focused on managing polycythemia vera, understanding hematocrit thresholds, reducing thrombotic risk, and reducing patient dependence on phlebotomy.

Read more

Prediction of resistance to hydroxyurea therapy in patients with polycythemia vera: a machine learning study (PV-AIM) validated in a prospective interventional phase IV trial (HU-F-AIM)

Posted on by

Published April 25, 2025

Florian H. Heidel, Valerio De Stefano, Matthias Zaiss, Jens Kisro, Eva Gückel, Susanne Großer, Mike W. Zuurman, Kirsi Manz, Kenneth Bryan, Armita Afsharinejad, Martin Griesshammer & Jean-Jacques Kiladjian

Abstract

Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thromboembolic (TE) risk and hematologic complications. Hydroxyurea (HU) serves as the most frequently used first-line cytoreductive therapy worldwide; however, resistance to HU (HU-RES) develops in a significant subset of patients, leading to increased morbidity and necessitating alternative treatments. This study, part of the PV-AIM project, employed machine learning techniques on real-world evidence (RWE) from the Optum® EHR database containing 82.960 PV patients to identify baseline predictors of HU-RES within the first 6–9 months of therapy. Using a Random Forest model, the study analyzed data from 1850 patients, focusing on laboratory parameters and clinical characteristics. Key predictive markers included red cell distribution width (RDW) and hemoglobin (HGB), showing the strongest association with HU-RES. A synergistic interaction between RDW and HGB was identified, enabling TE risk stratification. This study provides a robust framework for early detection of HU-RES using readily available clinical data, facilitating timely intervention. These findings underscore the importance of personalized treatment approaches in managing PV and highlight the utility of machine learning in enhancing predictive accuracy and clinical outcomes. Based on the results of PV-AIM we initiated an open-label, prospective, single-arm, interventional, phase IV study (HU-F-AIM) evaluating HU-resistance/intolerance. Validation of predictive biomarkers may facilitate identification of patients at risk of HU resistance who may benefit from alternative treatment options, possibly preventing ongoing phlebotomy during HU treatment, a frequent therapeutic choice in high-risk PV associated with early disease progression and increased thromboembolic complications. We propose an updated terminology that differentiates between true molecular resistance and clinical resistance, that may indicate the requirement for alternative therapeutic strategies.

Read more

 

Diagnosis and Management of PV and ET in Pediatric Populations Needs Improvement

Posted on by
Caleb Rans, PharmD
Publish Date

Polycythemia vera (PV) and essential thrombocythemia (ET) are rarely diagnosed in children, adolescents, and young adults. As the median age at diagnosis for these conditions is usually over 60 years, few pediatricians are familiar with their clinical, biological, and genetic features.1-3 Early diagnosis is essential to assess the need for specialized treatments and to prevent long-term complications, such as hemorrhage, thrombosis, or progression to secondary malignancies.1

In a 2-part study published in the European Journal of Pediatrics, Agathe Picard, MD, of the department of pediatric oncohematology at the Rennes University Hospital in France, and colleagues, analyzed practices around the diagnosis and management of pediatric patients with PV and ET in France.

Methodology and Study Design

In the first part of the study, a national practice survey about pediatric patients diagnosed with PV or ET was performed. The 8-question survey was sent to all pediatrician members of the leukemia committee of Société Française de lutte contre les Cancers et leucémies de l’Enfant et de l’adolescent (SFCE), and all hematologist members of France Intergroupe des Syndromes Myéloprolifératifs (FIM).

AYA [patients] should be referred to specialized units that consider the social, psychological, and educational needs of these patients.

In the second part, a retrospective cohort study was conducted at 7 pediatric oncohematology departments in western France. The researchers analyzed clinical, biological, and genetic data, as well as treatment and complication patterns from 17 pediatric patients with PV or ET, all of whom were diagnosed before the age of 18.

Read more

Rusfertide Cuts Phlebotomy Need in Polycythemia Vera: Andrew Kuykendall, MD

Posted on by

April 10, 2025

Author(s): Maggie L. Shaw, Andrew Kuykendall, MD

With an expected completion date sometime in June, the phase 3 VERIFY trial (NCT05210790) will soon conclude its investigation of rusfertide (Takeda) as add-on therapy to a patient’s current course of treatment for their polycythemia vera. The investigative agent has already received breakthrough therapy, orphan drug, and fast track designations from the FDA.

In this fourth part of a discussion with The American Journal of Managed Care®, Andrew Kuykendall, MD, clinical researcher at Moffitt Cancer Center and VERIFY investigator, speaks to the impressive patient-reported outcomes seen thus far.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

Can you summarize the key findings seen so far in the phase 3 VERIFY study?

Super exciting results that we saw. The study design, a lot of this was really built on a phase 2 study that was published in The New England Journal of Medicine that took patients with polycythemia vera who were requiring phlebotomies on a regular basis. That study basically put everyone on rusfertide and assessed over time their need for phlebotomy. There are a couple of different nuances to that study, but I would say the take home point of what we saw is that rusfertide very effectively eliminated the need for these patients that were regularly needing phlebotomies to need any phlebotomies at all—really rapidly reduced that and so certainly paved the way for designing a phase 3 clinical trial that could show that in comparison to standard therapy.

This trial took patients that had polycythemia vera that were requiring regular phlebotomy—so at least 3 over the preceding 28 weeks or 5 over the course of the prior year—and it randomized them to either stay on their standard therapy and add rusfertide or stay on their standard therapy and add a placebo. Everyone was treated in kind of the standard way, even if you were randomized to the “placebo arm”; that was just the standard therapy. If you were on cytoreductive therapy like hydroxyurea or interferon or ruxolitinib—these are agents we use to treat the disease as well—you stayed on those agents and you continued to get phlebotomies, as you would if you if you were kind of in routine clinical care. Then the other group did the same thing, but they added on rusfertide as a weekly subcutaneous injection. For 20 weeks, there was a a dose-finding period where rusfertide, the doses were increased based on hematocrit level and various different control of the disease.

The primary end point, at least in the US, was looking at the number of patients that were “phlebotomy eligible,” meaning that they needed a phlebotomy to control their disease—and that was being looked at between weeks 20 and 32. What we found is significantly more patients in the placebo group, so in the patients that were not receiving rusfertide, were “phlebotomy eligible” during that period of time. Another way to say that is, more patients in the rusfertide group did not need a phlebotomy during that that critical time period. Just another way of showing the control that rusfertide has, and that was the primary end point. Based on the phase 2 data, we certainly were optimistic that this was going to be reached.

Read more

Reducing Polycythemia Vera–Associated Thrombotic Risk Through Iron Regulation

Posted on by

April 1, 2025

Author(s): Maggie L. Shaw, Andrew Kuykendall, MD

The investigational rusfertide (Takeda), is currently being evaluated in the phase 3 VERIFY trial (NCT05210790) as an injectable therapeutic to treat polycythemia vera (PV) through achieving and sustaining hematocrit control. This agent has already breakthrough therapy, orphan drug, and fast track designations from the FDA.

In part 3 of a discussion, Andrew Kuykendall, MD, clinical researcher at Moffitt Cancer Center and VERIFY investigator, talks of rusfertide’s ability to free patients from being tethered to the need for regular phlebotomies and live a more viable life.

Part 1 and part 2 of this interview are also available to learn more about this potential novel PV treatment.

Read more

Understanding Hematocrit Thresholds in Polycythemia Vera Treatment

Posted on by

March 19, 2025

Author(s): Maggie L. Shaw, Andrew Kuykendall, MD

In early March, The American Journal of Managed Care® spoke with Andrew Kuykendall, MD, a clinical researcher at Moffitt Cancer Center who focuses on myeloproliferative neoplasms (MPNs), myelodysplastic syndrome/MPN overlap syndromes, and systemic mastocytosis. Kuykendall is an investigator on the phase 3 VERIFY trial (NCT05210790) of the injectable hepcidin mimetic rusfertide (Takeda) to treat polycythemia vera (PV) by enabling patients to achieve and sustain hematocrit control.1 Hematocrit is the measure of the percentage of red blood cells in the body.2

Treatment guidelines in PV currently recommend maintaining hematocrit below 45%, with a higher threshold for men vs women.2 For part 2 of this interview, Kuykendall explains the reasoning behind having different hematocrit thresholds.

In the first part of the interview, Kuykendall discussed how PV manifests and common ways to reduce its negative impact on patient quality of life.

Read more

Managing Polycythemia Vera to Reduce Risks and Improve Lives

Posted on by

March 5, 2025

Author(s): Maggie L. Shaw, Andrew Kuykendall, MD

Polycythemia vera is a classic myeloproliferative neoplasm and a chronic type of leukemia, which often leads to overproduction of various blood cells. Several medications are approved to treat this condition—among them ruxolitinib (Jakafi; Incyte), in December 2014,1 and ropeginterferon alfa-2b-njft (Besremi; PharmaEssentia), in November 20212—and others remain in clinical development. Rusfertide (Takeda) is currently being investigated in the phase 3 VERIFY trial (NCT05210790), with an estimate study complete date of June 2025.3 The hepcidin mimetic has already received breakthrough therapy, orphan drug, and fast track designations from the FDA.

In this interview, Andrew Kuykendall, MD, clinical researcher at Moffitt Cancer Center and a VERIFY investigator, breaks down how polycythemia vera manifests and common ways to reduce its negative impact on patient quality of life while reducing the risk of clinically worsening events.

Read more

Protagonist and Takeda Announce Positive Topline Results from Phase 3 VERIFY Study of Rusfertide in Patients with Polycythemia Vera

Posted on by

March 3, 2025

− Study met the primary endpoint, with a significantly higher proportion of clinical responders on rusfertide compared to placebo

− All four key secondary endpoints were met, including EU primary endpoint and patient-reported outcomes

− Rusfertide was generally well tolerated; no new safety findings were observed in the study

NEWARK, Calif. & OSAKA, Japan & CAMBRIDGE, Mass.–(BUSINESS WIRE)–Protagonist Therapeutics, Inc. (“Protagonist”) (NASDAQ:PTGX) and Takeda (TSE:4502/NYSE:TAK) today announced positive topline results for the Phase 3 VERIFY study, in which phlebotomy-dependent patients with polycythemia vera (PV) were randomized to treatment with either rusfertide or placebo, as an add-on to standard of care treatment. The study met its primary endpoint and all four key secondary endpoints. Rusfertide is a first-in-class investigational hepcidin mimetic peptide therapeutic, which has received Orphan Drug designation and Fast Track designation from the U.S. Food & Drug Administration (FDA).

Key findings from the study include:

  • The primary endpoint of the study was met, with a significantly higher proportion of clinical responders1 among rusfertide-treated patients with PV (77%) compared to those who received placebo (33%) during weeks 20-32; p<0.0001. The primary endpoint of the study was the proportion of patients achieving a response, which was defined as the absence of phlebotomy eligibility.
  • The first key secondary endpoint, which is the pre-specified primary endpoint for European Union (EU) regulators, was also met, with a mean of 0.5 phlebotomies per patient in the rusfertide arm compared to 1.8 phlebotomies per patient in the placebo arm during weeks 0-32; p<0.0001.
  • The other three pre-specified key secondary endpoints, namely hematocrit control2 and patient-reported outcomes using PROMIS Fatigue SF-8a3 and MFSAF TSS-74, were also achieved with statistical significance.
  • Rusfertide was generally well tolerated in the Phase 3 VERIFY trial, and safety was in line with previous rusfertide clinical studies. No new safety findings were observed in the study. The majority of adverse events were grade 1-2 injection site reactions and all serious adverse events reported were deemed to be not drug related. There was no evidence of an increased risk of cancer in rusfertide-treated patients compared to those on placebo.

“The positive results of the Phase 3 VERIFY study across the primary and all key secondary endpoints provide compelling evidence of the potential for rusfertide as a first-in-class erythrocytosis-specific agent to address unmet medical needs in patients with PV who are unable to achieve adequate hematocrit control despite standard of care treatments,” said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. “We plan to submit additional details of these promising results for presentation at upcoming medical conferences in 2025. We are immensely grateful to the patients, study staff and principal investigators who made the VERIFY study possible.”

Read more

Divesiran Is Tolerable and Shows Positive Early Signals in Polycythemia Vera

Posted on by

February 26, 2025

Author(s): Kyle Doherty

Fact checked by: Megan Hollasch

Divesiran (SLN124), a novel small interfering RNA (siRNA), was safe and displayed signals of efficacy in the treatment of patients with polycythemia vera, according to findings from the phase 1/2 SANRECO trial (NCT05499013).1

Initial results from SANRECO presented during the 2024 ASH Annual Meeting showed that divesiran reduced phlebotomy frequency in patients (n = 21). A total of 79 phlebotomies occurred across all patients prior to dosing; there were 5 phlebotomies during the treatment period and 2 during follow-up among all patients. Divesiran also induced hepcidin in all patients and decreased hematocrit in all cohorts of patients treated.

Additionally, patients did not experience any dose-limiting toxicities. Most treatment-emergent adverse effects (TEAEs) were grade 1 in severity (84%) and there were no TEAEs above grade 2 reported. There were also no treatment-related serious AEs or TEAEs leading to treatment discontinuation.

Divesiran is a first-in-class GalNAc-conjugated siRNA that targets TMPRSS6, a negative regulator of the HJV/BMP/SMAD signaling pathway that induces hepcidin expression. The agent is designed to have a long duration of action, and, notably, it’s target sequence is unique to TMPRSS6 and was selected to maximize TMPRSS6 knock down. Investigators hypothesized that inhibiting TMPRSS6 would raise hepcidin levels and lower iron delivery to the bone marrow, leading to reduced erythropoiesis.

Read more

4 Ways Polycythemia Vera Can Affect Your Quality of Life — and What You Can Do About It

Posted on by
By Jessica Migala
Published on February 14, 2025
by Walter Tsang, MD
Just like any chronic health condition, polycythemia vera (PV) can have a negative impact on your everyday life. Research has shown that PV is associated with a lower quality of life in measures, including health, cognitive, emotional, and physical functioning.

Symptoms such as fatigue, itchy skin, and mental health issues can make it difficult to function, but they can be managed. “This is a chronic condition that people can live with,” says Jacqueline S. Garcia, MD, a medical oncologist at Dana-Farber Cancer Institute in Boston.

Here are some common challenges of living with PV and ways to cope, so you can stay healthy and live well as you manage this condition.

1. Fatigue Can Interfere With Daily Activities

Fatigue is one of the most common symptoms of PV. “Polycythemia vera is a blood disorder that stems from an error in the bone marrow,” says Dr. Garcia. As a result, bone marrow overproduces red blood cells, causing the body to use up your iron supply. This results in iron deficiency, which leads to fatigue, she explains.
Another factor that can contribute to fatigue is phlebotomy treatment, which is a procedure that involves drawing blood to reduce blood cells and blood volume. A common side effect of this treatment is increased fatigue and iron deficiency, according to Garcia.

The degree of fatigue can vary from one person to another and depend on age, menopausal status, other health conditions — such as cardiovascular disease or diabetes — and more factors, says Garcia.

What to do about it: When it comes to polycythemia vera fatigue, research found that fatigue was a bigger problem for people who had a higher BMI, continued to drink alcohol or use tobacco, and didn’t exercise.

Maintaining healthy lifestyle habits may help you feel more energized every day. For instance, Garcia recommends exercising in moderation, as long as you have your doctor’s okay and don’t push yourself if you feel faint.

Read more