PharmaEssentia and MPN Advocacy & Education International Launch New Educational Initiative to Empower People Living With Polycythemia Vera (PV)

Posted on September 27, 2023September 27, 2023 by mpn_admin

Published: Sep 14, 2023

PV&ME™ campaign features personal stories from people living with PV and their journeys navigating the rare blood cancer

BURLINGTON, Mass. & EAST LANSING, Mich.–(BUSINESS WIRE)– PharmaEssentia USA Corporation, a subsidiary of PharmaEssentia Corporation (TPEx:6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, and MPN Advocacy & Education International, a leading advocacy group dedicated to providing the knowledge, support and resources patients will need as they adjust to living with a myeloproliferative neoplasm (MPN), today announced a new educational initiative for the MPN community called PV&ME. The goal of the campaign is to bring to light the unique and challenging experiences of living with polycythemia vera (PV) in the hopes of raising awareness, empowering patients to advocate for themselves and ensuring newly diagnosed patients feel supported in their journeys. PV&ME features the stories of four inspiring individuals – Buzz, Deb, Patti and Steven – living with this chronic cancer and their perspectives on navigating diagnosis, addressing burdensome symptoms and seeking comprehensive care.

PV is the most common MPN and a long-term, potentially life-threatening cancer that has had limited treatment options for many years. Patients with PV are at a more significant increased risk of developing thromboembolic events than the general population with cardiovascular disease, due to increased blood cell counts. They also have a long-term risk of progression to myelofibrosis or transformation to acute myeloid leukemia.^1-5

“People living with PV often face feelings of isolation as they navigate a long and confusing road to diagnosis and adjust to extreme fatigue or other often debilitating symptoms,” said Ann Brazeau, Chief Executive Officer, MPN Advocacy & Education International. “The stories shared in this new PV&ME campaign show just how important the right support and resources can be for this community. We hope this new initiative will help people with PV feel connected and empowered to advocate for themselves on their PV journeys.”

“At PharmaEssentia, we are committed to being an essential partner for the MPN community and know that a critical component of that is listening to and amplifying stories from individuals living with PV themselves,” said Raymond Urbanski, M.D., Ph.D., Senior Vice President and U.S. Head of Clinical Development and Medical Affairs at PharmaEssentia. “This MPN Awareness Day, we are proud to partner with MPN Advocacy & Education International to share these inspiring stories with the MPN community and help encourage patients to take a proactive approach in their care.”

The PV&ME educational video series launched on MPN Awareness Day (September 14) and can be found by visiting us.pharmaessentia.com/patients/patient-stories/. Throughout Blood Cancer Awareness Month, PharmaEssentia and MPN Advocacy & Education International will continue to share important educational content for the MPN community.

Follow PharmaEssentia USA on Twitter and LinkedIn for news and updates.

About Polycythemia Vera (PV)

Polycythemia vera (PV) is a cancer originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2.⁶

About PharmaEssentia

PharmaEssentia (TPEx: 6446), headquartered in Taipei, Taiwan, is a global and rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles, PharmaEssentia aims to deliver effective new biologics for challenging diseases in the areas of hematology and oncology, with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today PharmaEssentia is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung, Taiwan.

For more information about PharmaEssentia USA, visit the website, LinkedIn or Twitter.

About MPN Advocacy & Education International

MPN Advocacy and Education International provides educational programs, materials, and resources for patients, caregivers, physicians, and entire healthcare teams to improve their understanding of myelofibrosis, polycythemia vera, and essential thrombocythemia. They are dedicated to making a difference in the lives of those affected by MPNs and strive to grow awareness and advocate on behalf of the MPN community.

For more information about MPN Advocacy and Education International, visit the website, Facebook or Twitter.

PharmaEssentia, the PharmaEssentia logo, and PV&ME are trademarks or registered trademarks of PharmaEssentia Corporation.

¹ Griesshammer M, Kiladjian J-J, Besses C. Thromboembolic events in polycythemia vera. Ann Hematol. 2019;98:1071–82. DOI: 10.1007/s00277-019-03625-x
² Antithrombotic Trialists (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849-1860. https://doi.org/10.1016/S0140-6736(09)60503-1
³Yusef S, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. NEJM. 2016;374(21):2021-2031. DOI: 10.1056/NEJMoa1600176
⁴Risk and Prevention Study Collaborative Group; Roncaglioni M, et al. N-3 fatty acids in patients with multiple cardiovascular risk factors. NEJM. 2013;368:1800-1808. DOI: 10.1056/NEJMoa1205409
⁵ Barbui T, et al. In contemporary patients with polycythemia vera, rates of thrombosis and risk factors delineate a new clinical epidemiology. Blood. 2014;124:3021-3023. https://doi.org/10.1182/blood-2014-07-591610
⁶ Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 2015;5, e366; DOI:10.1038/bcj.2015.95

PharmaEssentia and MPN Advocacy & Education International Launch New Educational Initiative to Empower People Living With Polycythemia Vera (PV)

Posted on September 14, 2023September 14, 2023 by mpn_admin

PV&ME™ campaign features personal stories from people living with PV and their journeys navigating the rare blood cancer

September 14, 2023 08:00 AM Eastern Daylight Time

BURLINGTON, Mass. & EAST LANSING, Mich.–(BUSINESS WIRE)–PharmaEssentia USA Corporation, a subsidiary of PharmaEssentia Corporation (TPEx:6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, and MPN Advocacy & Education International, a leading advocacy group dedicated to providing the knowledge, support and resources patients will need as they adjust to living with a myeloproliferative neoplasm (MPN), today announced a new educational initiative for the MPN community called PV&ME. The goal of the campaign is to bring to light the unique and challenging experiences of living with polycythemia vera (PV) in the hopes of raising awareness, empowering patients to advocate for themselves and ensuring newly diagnosed patients feel supported in their journeys. PV&ME features the stories of four inspiring individuals – Buzz, Deb, Patti and Steven – living with this chronic cancer and their perspectives on navigating diagnosis, addressing burdensome symptoms and seeking comprehensive care.

Follow PharmaEssentia USA on Twitter and LinkedIn for news and updates.

About Polycythemia Vera (PV)

About PharmaEssentia

For more information about PharmaEssentia USA, visit the website, LinkedIn or Twitter.

About MPN Advocacy & Education International

For more information about MPN Advocacy and Education International, visit the website, Facebook or Twitter.

PharmaEssentia, the PharmaEssentia logo, and PV&ME are trademarks or registered trademarks of PharmaEssentia Corporation.

Patients With Polycythemia Vera Seek Guidance on Exercise

Posted on August 24, 2023August 24, 2023 by mpn_admin

August 23, 2023

Andrea S. Blevins Primeau, PhD, MBA

In a multicenter survey, patients with polycythemia vera (PV) shared their preferences and needs regarding physical activity (PA), including the frequency of PA per week and the type and location of activity. Notably, lower educational level was associated with higher levels of inactivity.

The study, which was published in the journal Cancer Medicine, surveyed 182 adult patients with PV about their disease burden and PA preferences and needs. The mean age of the cohort was 61 and 68% of patients were female. There were 57% of patients with more than 10 years of education and 48% were currently working. The mean time since diagnosis was 8 years.

Moderate-to-severe symptoms were present among 60% of patients, which most commonly included fatigue, concentration problems, and bone/muscle pain. Skin reactions, splenomegaly, tendency to bleed, and weight gain were also commonly reported symptoms.

There were 67% of patients who reported that they would like more information about PA. Patients with a lower educational level were significantly less likely to be engaged in PA at 50% compared with 69% of patients with a higher education level (P =.021).

Patients who were currently inactive preferred PA sessions 1 to 2 times per week for a duration of 15 to 45 minutes. Patients who already exercised, preferred PA 3 to 4 times per week for a duration of 30 to 60 minutes.

The majority of patients preferred individual training at 79%, whereas 40% preferred group training. The most common location that was preferred for PA was outdoors at 79% followed by at home at 56%. There was no significant difference in training setting or location among patients who were currently active or inactive.

The authors provided recommendations for the frequency, intensity, duration, and type of exercise for patient, as well as special recommendations depending on the symptom or side effect that an individual is experiencing. For example, yoga or tai-chi was recommended for patients with fatigue or concentration problems, whereas endurance training or yoga was recommended for patients with anxiety or depression.

Reference
Felser S, Rogahn J, Hollenbach L, et al. Physical exercise recommendations for patients with polycythemia vera based on preferences identified in a large international patient survey study of the East German Study Group for Hematology and Oncology (OSHO #97). Cancer Med. Published online August 9, 2023. doi: 10.1002/cam4.6413

Optimizing Hydroxyurea Management Among Patients With Polycythemia Vera

Posted on August 14, 2023August 14, 2023 by mpn_admin

August 8, 2023

Amber Denham

Results of a retrospective, real-world analysis determined that many patients with chronic myeloproliferative neoplasm (MPN) polycythemia vera (PV) received underdosed hydroxyurea, which led to lower complete response and toxicity rates, as well as proceeded with hydroxyurea regardless of poor clinical or hematological responses. These results highlight the need for more optimized [hydroxyurea] management and intervention in less-than-optimal responders.

“Hydroxyurea is currently the most used cytoreductive therapy for PV patients at high risk of thrombosis, with most patients achieving adequate control of the disease with acceptable tolerance,” Francesca Palandri, MD, Universitaria di Bologna, Bologna, Italy, and coauthors explained. “However, many patients may only obtain a poor response to [hydroxyurea] or develop drug-related toxicities during therapy.”

This study sought to define clinical characteristics associated with the achievement of complete response (CR) to hydroxyurea, investigate whether the type of suboptimal response may influence a decision to switch to ruxolitinib, and assess if a patient achieving CR to hydroxyurea would improve outcome parameters. The analysis included 563 patients with polycythemia vera treated with hydroxyurea for ≥12 months during an observational “PV-NET” Italian study. Among this patient population, 166 patients achieved complete response (CR), 264 achieved partial response (PR), and 133 achieved no response (NR).

In a multivariate analysis, the absence of splenomegaly (P = 0.03), pruritus (P = 0.002), and a median hydroxyurea dose of ≥1 g/day (P < 0.001) remained associated with CR. Overall, 283 patients who received either CR or PR continued hydroxyurea, and 114 patients switched to ruxolitinib. It was noted that many patients continued hydroxyurea despite a PR/NR and that splenomegaly and other symptoms were the main drivers of an early switch.

A median hydroxyurea dose of ≥1 g/day was correlated with more frequent adverse events. In the 449 patients who were receiving only hydroxyurea, rates of thrombosis, hemorrhages, progression, and overall survival (OS) were comparable among the CR, PR, and NR groups.

Palandri et al concluded, “Better [hydroxyurea] management, standardization of the criteria for and timing of responses to [hydroxyurea], and adequate intervention in poor responders should be advised.”

New Study Demonstrates Ropeginterferon Alfa-2b-njft Is a Cost-Effective Treatment Option for a Broad Range of Patients with Polycythemia Vera

Posted on August 14, 2023August 14, 2023 by mpn_admin

Published August 4, 2023

Analysis published in the Journal of Comparative Effectiveness Research shows ropeginterferon alfa-2b-njft provided a cost-effective benefit in quality-adjusted life years compared to a commonly used treatment pathway

BURLINGTON, Mass.–(BUSINESS WIRE)– PharmaEssentia USA Corporation, a subsidiary of PharmaEssentia Corporation (TPEx:6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced the publication of a cost-effectiveness analysis of ropeginterferon alfa-2b-njft (marketed as BESREMi^®) in the Journal of Comparative Effectiveness Research. The analysis, titled “Cost-Effectiveness of Ropeginterferon Alfa-2b-njft for the Treatment of Polycythemia Vera,” showed that ropeginterferon alfa-2b-njft provided a cost-effective benefit for a broad range of patients with polycythemia vera (PV) versus first-line hydroxyurea followed by ruxolitinib. Cost effectiveness was demonstrated in a modeled population including both low- and high-risk patients receiving first- or second-line treatment with ropeginterferon alfa-2b-njft.

“PV is a chronic blood cancer that requires lifelong therapy, which can prevent or delay negative clinical outcomes, but is also associated with additional costs to patients and payers. These new data demonstrate ropeginterferon alfa-2b-njft’s value not only to people living with PV, but also to the healthcare system at large,” said Dr. Aaron Gerds, MD, MS, Medical Director at Case Comprehensive Cancer Center and lead study author. “This study shows ropeginterferon alfa-2b-njft is a cost-effective treatment option over the modeled lifetime and that earlier initiation of treatment of PV with effective therapy can translate to more favorable cost to benefit ratios.”

PV is the most common myeloproliferative neoplasm (MPN) and a long-term, potentially life-threatening disease with limited approved treatment options. Patients with PV are at risk for disease progression to myelofibrosis (post-PV MF) or transformation to blast phase (MPN-BP) which is akin to acute myeloid leukemia^1-3. Patients are also at an increased risk for arterial and venous thromboembolic events (TEs) which are associated with higher mortality, lower quality of life, and higher healthcare costs^4-7.

This new study used an economic model developed from the United States healthcare system perspective. Inputs were informed by the data from randomized clinical trials, including the PROUD-PV and CONTINUATION-PV studies, and from real-world sources. The model compared ropeginterferon alfa-2b-njft used either as first- or second-line therapy versus an alternative treatment pathway of first-line hydroxyurea followed by ruxolitinib. To reflect the long-term consequences of treating PV, results were presented over a lifetime horizon.

Findings from the study conclude ropeginterferon alfa-2b-njft is a cost-effective treatment option for a broad range of patients with PV, including both low- and high-risk patients and patients with and without prior cytoreductive treatment with hydroxyurea. Of note:

These data show that over the modeled lifetime, patients who receive ropeginterferon alfa-2b-njft have more years alive (0.4), higher quality-adjusted life years (QALYs) (0.4), and higher cost ($60,175) as compared to the alternative treatment pathway. Weighing the additional costs versus the additional QALY gains results in a cost per QALY of $141,783.
This cost per QALY is less than a standard willingness to pay threshold of $150,000 per QALY⁸.
In this study, treating patients at a younger age or those with low-risk disease led to more cost-effective results, suggesting that earlier initiation of treatment of PV with effective therapy can translate to more favorable cost to benefit ratios.
The model was sensitive to treatment costs, the percentage of patients who discontinue hydroxyurea, the percentage of ropeginterferon alfa-2b-njft users who switch to monthly dosing, the percentage of ropeginterferon alfa-2b-njft users as 2nd line treatment, and the treatment response rates.

“Ropeginterferon alfa-2b-njft has demonstrated safety and efficacy in studies including both low- and high-risk patients and patients with and without prior cytoreductive treatment with HU. Recently, the National Comprehensive Cancer Network (NCCN) updated their treatment guidelines to include ropeginterferon as a preferred treatment regimen for both low- and high-risk PV patients⁹. As ropeginterferon continues to be more widely used in clinical practice, this study was imperative to demonstrate the cost-effectiveness of ropeginterferon alfa-2b-njft for a broad range of patients with PV,” said Raymond Urbanski, M.D., Ph.D., Senior Vice President and U.S. Head of Clinical Development and Medical Affairs at PharmaEssentia. “This analysis also underscores the importance of treating low-risk patients and patients early in their disease journey to help minimize more severe events and their corresponding costs to the healthcare system.”

The full benefits of ropeginterferon alfa-2b-njft may not be fully captured in the model, and in particular, data on disutility of phlebotomy are lacking. Although some patients may tolerate regular phlebotomies, others can experience iron deficiency which can negatively impact quality of life. While the results from a scenario analysis incorporating a small decrement in utility had minimal impact on the cost-effectiveness results, due to the lack of data in this area, this estimate remains conservative. This study took a U.S. healthcare perspective, and the results may not generalize to other countries given the differences in healthcare resource use, costs and cost-effectiveness thresholds.

About Polycythemia Vera (PV)

About BESREMi^® (ropeginterferon alfa-2b-njft)

BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients.

BESREMi has orphan drug designation for the treatment of polycythemia vera (PV) in adults in the United States. The product was approved by the European Medicines Agency (EMA) in 2019, in the United States in 2021, and has recently received approval in Taiwan and South Korea. The drug candidate was invented by PharmaEssentia and is manufactured in the company’s Taichung plant, which was cGMP certified by TFDA in 2017 and by EMA in January 2018. PharmaEssentia retains full global intellectual property rights for the product in all indications.

NCCN Guidelines Update Recommends Ropeginterferon Alfa-2b for Polycythemia Vera

Posted on July 10, 2023July 10, 2023 by mpn_admin

July 7, 2023

Rose McNulty

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology was recently updated to include ropeginterferon alfa-2b (Besremi; PharmaEssentia) as a preferred treatment option for patients with high- and low-risk polycythemia vera (PV), according to a press release from PharmaEssentia USA Corporation.¹

The updated guidelines recommend ropeginterferon alfa-2b and designate the recommendation as category 2A, which signifies a uniform NCCN consensus that ropeginterferon alfa-2b is an appropriate intervention for patients with PV. The agent was granted FDA approval for the treatment of PV in 2021 and was the first FDA-approved treatment indicated for PV regardless of previous treatment.²

“Importantly, the NCCN Guidelines update includes moving [ropeginterferon alfa-2b] to preferred status, reinforcing to treating physicians and patients that with its broad utility, [ropeginterferon alfa-2b] is recommended for proactively treating PV,” said John Mascarenhas, MD, professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai in New York, in a statement.¹

PV, a rare hematological malignancy and the most common chronic myeloproliferative neoplasm, is characterized by overproduction of red blood cells in bone marrow that can lead to elevated white blood cell and platelet counts. Ropeginterferon alfa-2b is a monopegylated, long-acting interferon that blocks the signals that cause malignant cells to multiply.

The FDA approval of ropeginterferon alfa-2b was based on safety data from the PEGINVERA (NCT01193699) trial; PROUD-PV (NCT01949805) and its open-label extension portion, CONTINUATION-PV (NCT02218047); and efficacy data from the PEGINVERA clinical study program, according to a press release following the 2021 approval.³

Efficacy results showed that 61% of patients experienced complete hematological response—defined as hematocrit less than 45% without phlebotomy for at least 2 months since the patient’s last phlebotomy, platelet counts of 400 x 109/L or less, leukocytes of 10 x 109/L or less, and normal spleen size—following 7.5 years of treatment with ropeginterferon alfa-2b. Based on objective laboratory parameters, 80% of patients achieved a hematological response in the study.

As far as safety, ropeginterferon alfa-2b was shown tolerable in a pooled safety population, with the most common adverse reactions with incidence of 40% or higher being influenza-like illness, arthralgia, fatigue, pruritis, nasopharyngitis, and musculoskeletal pain. Serious adverse reactions occurring in less than 4% of cases were urinary tract infection, transient ischemic attack, and depression.

New data from the PROUD-PV and CONTINUATION-PV studies were presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition last December, adding to evidence in support of ropeginterferon alfa-2b for PV. In one abstract, the majority of both low- and high-risk patients with PV (85.7% and 75.0%, respectively) in the CONTINUATION-PV trial did not require phlebotomy for the entire sixth year of treatment.⁴

“This recent update to treatment guidelines by NCCN represents the community’s recognition of the value of [ropeginterferon alfa-2b] as a therapeutic option for all adults with PV, regardless of their treatment history,” said Raymond Urbanski, MD, PhD, US. Head of Clinical Development and Medical Affairs at PharmEssentia. “Given its deep, durable control over the disease beyond the symptoms, we’re continuing to study [ropeginterferon alfa-2b] in PV, as well as other myeloproliferative neoplasms (MPNs) and hematologic malignancies.”

References

1. NCCN Clinical Practice Guidelines in Oncology updated to recommend Besremi (ropeginterferon alfa-2b-njft) as a preferred intervention for polycythemia vera. News release. PharmaEssentia USA Corporation. May 23, 2023. Accessed May 24, 2023. https://us.pharmaessentia.com/wp-content/uploads/2023/05/NCCN_Guidelines_Update_Press_Release_May-23-2023.pdf

2. FDA approves treatment for rare blood disease. News release. FDA. November 12, 2021. Accessed July 6, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-rare-blood-disease

3. US FDA approves Besremi (ropeginterferon alfa-2b-njft) as the only interferon for adults with polycythemia vera. News release. PharmaEssentia Corporation. November 12, 2021. Accessed July 6, 2023. https://us.pharmaessentia.com/wp-content/uploads/2021/11/BESREMi-FDA-Approval-November-12-2021.pdf

4. Caffrey M, Shaw ML, Klein H. ASH 2022: rare diseases & blood disorders. Am J Manag Care. 2023;29(SP1):SP42-SP46.

Dr Kremyanskaya on the Efficacy of Rusfertide in Phlebotomy-Dependent Polycythemia Vera

Posted on June 27, 2023June 27, 2023 by mpn_admin

June 16, 2023

Marina Kremyanskaya, MD, PhD

Marina Kremyanskaya, MD, PhD, assistant professor of medicine, hematology, and medical oncology, Icahn School of Medicine, Mount Sinai, medical director, Inpatient Oncology Unit, The Mount Sinai Hospital, discusses key efficacy data for rusfertide (PTG-300) in the phase 2 REVIVE trial (NCT04057040) of phlebotomy-dependent polycythemia vera.

Polycythemia vera is a specific type of erythrocytosis that also features systemic symptoms and a high risk of thromboembolic and/or cardiovascular (CV) complications. High levels of the iron-regulator hepcidin have been implicated in uncontrolled red blood cell formation.

The REVIVE trial compared the ability of the first-in-class hepcidin mimetic rusfertide vs placebo to control erythrocytosis in patients with polycythemia vera who had previously received 3 or more phlebotomies in 28 weeks with or without concurrent cytoreductive therapy. The trial was composed of a dose-finding stage (part 1), blinded randomized withdrawal (part 2), and an open-label extension portion (part 3).

Patients in part 1 received a weekly subcutaneous dose of rusfertide that was individually adjusted to achieve a hematocrit level below 45% (range, 10 mg-120 mg). In part 2, patients were randomized to continue rusfertide or to receive placebo. The study’s primary end point was efficacy as characterized by the proportion of responders in part 2, Kremyanskaya says. Responses were achieved if patients had a hematocrit level below 45% without phlebotomy eligibility, did not receive therapeutic phlebotomy, and had completed 12 weeks of treatment, she explains.

Results from the randomized withdrawal phase were presented at the 2023 EHA Congress and demonstrated that rusfertide produced a significantly higher percentage of responders vs placebo, Kremyanskaya reports. These percentages were 69.2% (n = 18/26) with rusfertide vs 18.5% (n = 5/27) with placebo. Additionally, most patients on the study had low ferretin levels at baseline, indicating iron deficiency, Kremyanskaya states. After treatment with rusfertide, ferretin levels were normalized and maintained for many of these patients, she says.

Analysis of symptom improvement was based on data from part 1, as the majority of patients in the placebo arm of part 2 discontinued treatment prior to the 12-week mark, Kremyanskaya continues. Rusfertide treatment significantly improved the rate and severity of problems with concentration, itching, fatigue, and inactivity, which tend to be moderate or severe at baseline. Regarding safety, the agent was generally well tolerated, Kremyanskaya concludes.

Disclosures: Dr Kremyanskaya reported receiving honoraria and being on the advisory board for Protagonist Therapeutics, Inc.

Rusfertide Offers Durable Hematocrit Control in Phlebotomy-Dependent Polycythemia Vera

Posted on June 14, 2023June 14, 2023 by mpn_admin

June 11, 2023

Caroline Seymour

Rusfertide (PTG-300) demonstrated freedom from phlebotomy, sustained hematocrit control, and 12-week treatment completion in 69.2% (n = 18/26) vs 18.5% (n = 5/27) of patients with phlebotomy-dependent polycythemia vera who received placebo (P = .0003), meeting the primary end point of the phase 2 REVIVE trial (NCT04057040). Findings were presented at the 2023 EHA Congress.

“The REVIVE study demonstrated significantly higher efficacy with rusfertide compared with placebo in subjects with polycythemia vera,” said Marina Kremyanskaya, MD, PhD, lead study author and assistant professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai in New York, New York, in a presentation of the data. “Current standard-of-care therapy in polycythemia vera does not consistently maintain hematocrit below 45%, thereby potentially increasing the risk of thromboembolic events. Rusfertide has the potential to consistently maintain hematocrit [levels] below 45%.”

Polycythemia vera is a myeloproliferative neoplasm (MPN) that produces red blood cells in excess and is often marked by elevated hematocrit. Hematocrit, when uncontrolled, can lead to higher fatality from cardiovascular causes or thrombotic events. Although guidelines from the National Comprehensive Cancer Network and European LeukemiaNet state that hematocrit should be maintained below 45%, current standard-of-care therapy fails to do so in most patients.

Hepcidin is a peptide hormone that controls iron availability for red blood cell formation. Rusfertide is a novel hepcidin mimetic that mirrors the effects of hepcidin on erythropoiesis, representing a potential add-on therapy to standard therapy with improved activity. This hypothesis was tested in the phase 2 REVIVE trial.

To be eligible for enrollment in the study, patients had to have phlebotomy-dependent polycythemia vera per 2016 World Health Organization criteria, having received at least 3 phlebotomies in 28 weeks with or without concurrent cytoreductive therapy. Additionally, all patients had to be phlebotomized to hematocrit levels below 45% prior to the first dose of rusfertide to standardize the starting hematocrit.

The study consisted of 3 parts: dose finding, blinded randomized withdrawal, and open-label extension. Rusfertide was administered subcutaneously in doses ranging from 10 mg to 120 mg weekly. In part 1, rusfertide was titrated for the first 16 weeks to determine the clinically effective dose. Efficacy was evaluated in weeks 17 to 28. In part 2, patients were randomly assigned 1:1 to receive active or placebo doses of rusfertide in weeks 29 to 41. Study treatment continued in part 3 for up to 3 years.

Safety and efficacy served as key end points of the trial. Efficacy was characterized by the proportion of responders in part 2, defined by the proportion of patients who maintained hematocrit below 45% and the percentage reduction in phlebotomies. Patient outcomes were evaluated with the MPN Symptoms Assessment Form Total Symptom Score.

A total of 70 patients were included in the dose-finding portion of the research. Fifty-nine patients were treated in part 2, 53 of which were included in the primary efficacy analysis set. Fifty-two patients are ongoing treatment in part 3

Regarding baseline characteristics of those included in part 2, most patients were male, above the age of 50 years at diagnosis, had polycythemia vera for approximately 5 years, and received hydroxyurea as the primary means of cytoreductive therapy. Across the arms, 52.7% of patients were high risk and 47.4% were low risk. Body mass index was 30.1 ± 5.76 kg/m2 and 28.7 ± 4.55 kg/m2 in the placebo and rusfertide arms, respectively.

Additional findings demonstrated similar benefit in time to treatment failure with rusfertide in responders (P < .0001), patients ineligible for phlebotomy plus hydroxyurea (P < .0001), and those with hematocrit under 45% (P < .0001).

Kremyanskaya also explained that rusfertide led to meaningful reductions in the need for phlebotomy, both with phlebotomy only (n = 37) and phlebotomy plus cytoreductive therapy (n = 33).

Although the focus of the presentation centered around outcomes in part 2, investigators also evaluated symptom improvement in part 1. Notably, moderate or severe symptoms of problems with concentration (P =.0018), itching (P = .0054), fatigue (P =.0074), and inactivity (P =.0005) were all improved following treatment with rusfertide. Kremyanskaya noted that meaningful comparison of symptom improvement was not possible in part 2 because most patients who were randomized to placebo discontinued prior to the 12-week symptom assessment.

In terms of safety, Kremyanskaya stated that rusfertide was “generally well tolerated.” Treatment-emergent adverse effects (TEAEs) included injection site erythema (64.3%), injection site pain (41.4%), injection site pruritus (40.4%), fatigue (31.4%), injection site mass (25.7%), pruritus (25.7%), arthralgia (24.3%), injection site swelling (24.3%), dizziness (22.9%), headache (22.9%), nausea (22.9%), anemia (20.0%), COVID-19 (20.0%), injection site irritation (18.6%), and injection site bruising (15.7%). Most events were grade 1/2 (83%), and 17% of patients experienced grade 3 events. No grade 5 events occurred.

“Most common TEAEs were injection site reactions, which decreased in incidence with continued treatment,” Kremyanskaya noted. “Additionally, events were localized, grade 1 or 2 in severity, and generally did not lead to treatment discontinuation,”

Two treatment-related events of mild thrombocytosis and recurrent grade 1 injection site erythema led to treatment discontinuation.

Patients who completed the REVIVE study will be eligible to enroll in PTG-300-21, a separate, 2-year follow-on extension trial. The agent is also under evaluation in the phase 3 VERIFY trial (NCT05210790), where it is being compared with placebo in patients with polycythemia vera maintaining hematocrit control and in improving symptoms of disease.

Disclosures: Dr Kremyanskaya reported receiving honoraria and being on the advisory board for Protagonist Therapeutics, Inc.

Reference

Kremyanskaya M, Kuykendall A, Pemmaraju N, et al. Targeted therapy of uncontrolled erythrocytosis in polycythemia vera with the hepcidin mimetic, rusfertide: – blinded randomized withdrawal results of the REVIVE study. Presented at: 2023 EHA Congress; June 8-11, 2023; Frankfurt, Germany. Abstract LBA2710.