Rusfertide Improves Responses in Phlebotomy-Dependent Polycythemia Vera

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Caroline Seymour

Patients with phlebotomy-dependent polycythemia vera, a type of myeloproliferative neoplasm, treated with rusfertide experienced a response rate of 60% (n = 18/30) compared with 17% (n = 5/29) in those who received placebo (P = .002), according to updated findings from part 2 of the phase 2 REVIVE trial (NCT04057040) published in the New England Journal of Medicine.1

The international trial was designed with 3 parts: a 28-week, open-label, dose-finding portion in which rusfertide was added to a patient’s ongoing therapy of phlebotomy alone or cytoreductive therapy with optional phlebotomy; a double-blind, randomized withdrawal portion wherein patients were randomly assigned to receive rusfertide or placebo for 12 weeks (weeks 29 to 41); and an open-label extension period following patients on rusfertide therapy for up to 3 years.

Findings from part 1 showed that the estimated mean number of annual phlebotomies was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). Moreover, the mean maximum hematocrit level was 44.5±2.2% during part 1 vs 50.0±5.8% during the 28 weeks before the first dose of rusfertide. Patient quality of life was also improved on rusfertide, with a lower severity of disease-related symptoms.

“Rusfertide appears to represent a significant step forward in treating [patients with] polycythemia vera through its unique approach of limiting the amount of iron available for blood cell production,” Marina Kremyanskaya, MD, PhD, an associate professor of medicine (hematology and medical oncology) at Icahn School of Medicine at Mount Sinai in New York, New York, and lead author of the study, stated in a news release.2 “Pending further clinical studies, this injectable agent could become a valuable therapeutic tool for a disease which many patients and their physicians struggle to bring under control.”

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Combination Therapies and New Research Drive Progress in Myelofibrosis

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Jordyn Sava

2023 brought a wave of positive developments for patients with myeloproliferative neoplasms (MPNs), particularly myelofibrosis. According to Raajit K. Rampal, MD, PhD, one study of particular interest was the phase 3 MANIFEST-2 trial (NCT04603495) of ruxolitinib (Jakafi) with pelabresib (CPI-0610).1 

This study, in addition to the TRANSFORM-1 trial (NCT04472598), showed significant improvement in spleen size and potential benefits in symptom reduction with combination therapies compared with single-agent treatments, suggesting that these combinations could become valuable options for treating patients with myelofibrosis upfront.1,2

Other studies, including early data of TP-3654 and selinexor (Xpovio), show potential for further advancements in myelofibrosis treatment.

“There is a lot to be excited about for the first time in a very long time. There are all of these other small molecule inhibitors in clinical trials [and] I think we will learn a lot from that,” said Rampal, hematologic oncologist at Memorial Sloan Kettering Cancer Center, in an interview with Targeted OncologyTM.

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Ryvu Therapeutics to Present Preclinical Data on RVU120 and Synthetic Lethality Programs at the 2024 AACR Annual Meeting

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Published: Mar 06, 2024

  • Updated preclinical data will be presented from Ryvu’s synthetic lethality pipeline, including PRMT5 inhibitors in MTAP-Deficient cancers, WRN inhibitors for the treatment of microsatellite unstable (MSI-H) tumors, and Ryvu’s cutting-edge synthetic lethality platform based on primary cancer cells.
  • Poster presentation to highlight the synergistic effects of RVU120 in combination with ruxolitinib in myeloproliferative neoplasms.
  • Ryvu’s partner Menarini to present data on MEN1703 (SEL24), demonstrating promising anti-tumor activity in preclinical models of myelofibrosis both as a single agent and combined with ruxolitinib.

KRAKOW, Poland, March 6, 2024 /PRNewswire/ — Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, announced today that preclinical data from its synthetic lethality pipeline and RVU120 project, as well as on MEN1703 (SEL24), will be presented at the upcoming 2024 AACR Annual Meeting, scheduled for April 5-10 in San Diego, California.

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Patients With Myelofibrosis Are at Higher Risk for Poor Cardiovascular Outcomes After Heart Failure Hospitalization

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Grace Taylor

03/05/2024

Patients with myeloproliferative neoplasms (MPN) are at high risk of cardiovascular (CV) disease, including heart failure (HF). Those with myelofibrosis in particular have a higher chance of experiencing HF. In a study presented at the 2023 ASH Annual Meeting & Exposition, Orly Leiva, New York University Grossman School of Medicine, Boston, Massachusetts, and colleagues examined CV outcomes for patients with MPN (essential thrombocythemia [ET], polycythemia vera [PV], or MF) who were hospitalized for HF.

The authors completed a retrospective analysis using data from the National Readmission Database (NRD). They used ICD-10 codes to identify adult patients with a history of MPN who had a primary diagnosis of HF from 2017 and 2018 (N = 4632). Of these patients, 2639 had ET, 1109 had PV, and 884 had MF.

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Advocacy: PDABs on Our Radar

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In response to rising drug costs, some states are creating Prescription Drug Affordability Boards, or PDABs, that have varying degrees of oversight. PDABs are tasked with determining reasonable drug prices based on things such as: if the price affects a patient’s access to a drug, if there are other drugs proven to do the same thing for a cheaper price, and what the drug manufacturer charges. Additionally, special consideration is to be taken for drugs that treat rare conditions, and input from patient communities is supposed to be included in the decision-making process.

Colorado was one of the first states to create a PDAB back in 2021 and they are currently reviewing 5 drugs, one of which is an orphan drug used by cystic fibrosis patients. Each state decides how they will select the drugs for review. Other states with PDABs are Maine, Maryland, Minnesota, New Hampshire, Oregon, and Washington. States that introduced PDAB legislation in 2023 are Connecticut, Michigan, New Jersey, New Mexico, Rhode Island, Vermont, and Virginia.

As a patient advocacy and education organization, we want to ensure that our MPN community is informed about PDABs and how they could impact your access to MPN drugs. We also want to make certain that the MPN patient voice is central to any board if an MPN drug comes up for review. Most importantly, we want to make sure that every MPN patient benefiting from an MPN drug has access to it.

We want to hear from you! Are you in a state with a Prescription Drug Affordability Board? If so, do you know how your board chooses which drugs will be reviewed or which drugs are currently up for review? Let us know by contacting Ann Brazeau at abrazeau@mpnadvocacy.com.
Stay tuned as we learn more about PDABs and make plans to ensure the MPN voices are heard!

A Patient Story: If I Only Knew

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I’m 38 today and was diagnosed with ET at age 21 while in college in 2007, following a routine blood test. I took the blood test so that I could donate bone marrow to earn money ($400 at the time) for an upcoming study abroad trip. Apart from the increased platelet count, I did not have other noticeable symptoms.  The blood test results indicated an increased platelet count, and I was not permitted to donate bone marrow.  I underwent a bone marrow biopsy many months later, which confirmed the diagnosis of ET. I am JAK2+.
Between that time period in college and today, I’ve been on and off hydroxyurea, on and off baby aspirin, got married, had two children, learned more about bleeding and other symptoms related to high platelet counts and have met new members of the MPN community. I wish I knew then how much hormone levels and clotting issues can impact women’s reproductive health. Interestingly, I learned after my son was born that I also carry the gene for hemophilia A, an incurable bleeding disorder. Call me if you’d like to talk about both clotting or bleeding!
These days, I do occasionally experience incredible fatigue and frequently find myself scratching itchy skin (particularly after the shower) and have noticed some vision changes but am not sure if that can be attributed to ET. Today, I’m so grateful for the knowledge I’ve gained and the support available to me in the MPN community, especially MPN Advocacy and Education International.

Dr Jennifer Vaughn: Patients With MPN, MDS Should Discuss Long-Term Priorities Upfront

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Laura Joszt, MA
Justina Petrullo
With most patients with myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDS) experiencing long-term, chronic disease, it’s important to discuss their priorities and set up the relationship with their providers upfront, explained Jennifer Vaughn, MD, assistant professor in the division of hematology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute.

About 1 in 5 Hematologic Cancer Patients Had Severe COVID-19, Despite Vaccination

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Leah Lawrence

In a study of more than 6000 patients with hematologic cancers, 21% developed severe COVID-19, despite being vaccinated. Researchers reported these results in JAMA Network Open.

The study included 6122 patients from the national Veterans Health Administration who had hematologic cancers. All patients had been vaccinated against COVID-19 but had a confirmed case of COVID-19 between January 1, 2021, and September 30, 2022.

The patients had chronic lymphocytic leukemia (CLL; n=1206) or other non-Hodgkin lymphomas (NHLs; n=1731), plasmacytoid neoplasms (n=1014), myeloproliferative neoplasms (MPNs; n=1144), myelodysplastic syndromes (MDS; n=518), chronic myeloid leukemia (CML; n=180), acute myeloid leukemia (AML; n=172), or Hodgkin lymphoma (n=157).

A total of 1301 paints (21.3%) had severe COVID-19, which was defined as dying within 28 days of SARS-CoV-2 infection, requiring mechanical ventilation, or requiring hospitalization with the use of dexamethasone, evidence of hypoxemia, or the use of supplemental oxygen.

The proportion of patients with severe COVID-19 was similar among those with lymphoid malignancies (21.6%) and those with myeloid malignancies (20.5%). The rate of severe COVID-19 was highest in patient with MDS (28.2%) and lowest in patients with Hodgkin lymphoma (12.1%).

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Non-Driver Gene Mutations Have Adverse Prognostic Impact in Primary Myelofibrosis

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Lauren Dembeck, PhD

A study published in the American Journal of Hematology has confirmed the adverse prognostic impacts of numerous non-driver gene mutations in primary myelofibrosis (PMF).

Researchers analyzed the impact of non-driver somatic mutations in patients with PMF treated at 60 institutions in Spain. Targeted next-generation sequencing (NGS) sequencing evaluating up to 56 non-myeloproliferative neoplasm driver genes was conducted. Of those, the team focused on 20 genes consistently analyzed across NGS panels. Only pathogenic or likely-pathogenic genetic variants with a variant allele frequency (VAF) higher than 1% were considered mutations.

A total of 312 patients with PMF according to World Health Organization criteria at the time of diagnosis and with availability of NGS data were included in the analysis. The median age of the cohort was 68 years. At a median follow-up duration of 4 years, 9% of patients had progressed to acute myeloid leukemia, and 47% had died.

Overall, 72% of patients had non-driver mutations, with 47% having 2 or more mutations (range, 0-7). The most frequent mutations detected were in ASXL1 (34%), TET2 (22%), SRSF2 (17%), U2AF1 Q157 (9%), CBL (8%), EZH2 (7%), TP53 (6%), DNMT3A (6%), and SETBP1 (5%).

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Years After Genetic Finding, Drugs Targeting CALR-Mutant Myeloproliferative Neoplasms Enter Trials

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Feb 29, 2024 | Catherine Shaffer

NEW YORK – More than a decade after mutations in the CALR gene were first linked to the development of myeloproliferative neoplasms, CALR-targeted drug candidates are advancing to Phase I clinical trials.

If these drugs reach the market, they could provide a treatment option for a group of patients with myelofibrosis and essential thrombocythemia who typically must wait until their condition turns serious to attempt a risky stem cell transplant.

About 300,000 patients in the US have myeloproliferative neoplasms. Kapila Vigas, CEO of the MPN Research Foundation, said patients can have very different presentations of the disease, and it can take “years or decades” to get a diagnosis. Although myeloproliferative neoplasms are classified as chronic cancers that patients can live with for many years with blood count monitoring, Vigas said some patients can abruptly progress, and their condition can become serious.

“That uncertainty is really concerning to patients,” Vigas said. “We think from a psychosocial perspective, it’s worse than an acute cancer because while cancer may be more serious, it’s predictable, and there’s a plan and a protocol, whereas when you’re diagnosed with [a myeloproliferative neoplasm] watch and wait is almost a first-line approach. It just adds to the anxiety.”

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