More than 50 Abstracts from Incyte’s Robust Oncology Portfolio to be Featured at the 64th ASH Annual Meeting

Posted on November 7, 2022November 7, 2022 by mpn_admin

November 3, 2022 10:24 AM Eastern Daylight Time

– Plenary Scientific Session to highlight Incyte-discovered novel anti-mutant CALR-targeted monoclonal antibody INCA033989

– Data from three of the Company’s LIMBER studies evaluating ruxolitinib in combination with parsaclisib and its ALK2 and BET inhibitors to be presented

– Incyte to host an in-person analyst and investor event on Sunday, December 11, 2022, from 8:00-9:30 p.m. CT to discuss key data presentations at ASH

WILMINGTON, Del.–(BUSINESS WIRE)–Incyte (Nasdaq:INCY) will present data from its oncology portfolio at the upcoming 64^th American Society of Hematology Annual Meeting (ASH 2022), held December 10-13, 2022, in New Orleans and virtually. More than 50 abstracts featuring Incyte compounds will be presented, highlighting its robust portfolio and clinical development programs.

“The data to be presented at ASH illustrate the scientific depth and progress made across several of our key programs, including ruxolitinib (Jakafi^®), parsaclisib, tafasitamab (Monjuvi^®/Minjuvi^®), pemigatinib (Pemazyre^®) as well as our LIMBER studies, which are evaluating new targets and combination strategies to expand treatment options for patients with myeloproliferative neoplasms (MPNs) and graft-versus-host disease (GVHD),” said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapeutics, Incyte. “Notably, the plenary scientific session at ASH will feature INCA033989, an Incyte-developed, novel anti-mutant CALR-targeted monoclonal antibody. Additionally, a combination study evaluating ruxolitinib with parsaclisib will be featured as an oral presentation, and two studies evaluating ruxolitinib with INCB000928 and INCB057643, our ALK2 and BET inhibitors, respectively, will also be presented. These presentations highlight our advancing portfolio and comprehensive approach to identifying potential new treatments for patients with cancer.”

Biden to sign executive order aimed at lowering drug costs

Posted on October 18, 2022October 18, 2022 by mpn_admin

October 14, 2022

By: Oriana Gonzalez

President Biden on Friday will sign an executive order directing administration officials to consider further actions to lower prescription drug costs, the White House announced.

Why it matters: With less than a month before the midterms, Biden is focusing on health care costs to help position Democratic candidates.

The big picture: Biden’s order would compliment the Inflation Reduction Act and specifically, the provision allowing the federal government to negotiate some prescription drug prices.

However, polls show that while the public is familiar with the law, they are unaware of its key health provisions.
Still, many of the law’s goals have strong public support, including limiting out-of-pocket prescription drug costs for people on Medicare and capping monthly out-of-pocket insulin costs for Medicare recipients.

State of play: The executive order directs the Department of Health and Human Services to “explore additional actions” it can take to lower prescription drug costs.

HHS will have 90 days to submit a report on how it will use new models of health care payment and delivery to lower drug costs “and promote access to innovative drug therapies for beneficiaries enrolled in the Medicare and Medicaid programs.”

Patient-reported outcomes of patients with myelofibrosis or essential thrombocythemia enrolled in the MOST study

Posted on October 11, 2022October 11, 2022 by mpn_admin

Ellen Ritchiea , Anas Al-Janadib, Craig Kessler, Robyn Scherberd, Tricia Kalafutd, Haobo Rend and Ruben Mesa

Introduction
Myelofibrosis (MF) and essential thrombocythemia (ET) are acquired Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), a rare group of malignant blood disorders characterized by abnormal clonal proliferation of at least one myeloid cell line
[1,2]. Hallmark characteristics of MF include splenomegaly, burdensome constitutional symptoms, cytopenia, and progressive bone marrow fibrosis [3,4]. ET is associated with increased platelet and megakaryocyte production, and increased risk of vascular events such as thrombosis and bleeding [1,3].

Patients with MF or ET report a range of symptoms such as abdominal discomfort, bone pain, fatigue, itching, night sweats, unexplained weight loss, and/or fever [5–9]. Additional symptoms common to MF are often related to spleen enlargement and include abdominal pain, left subcostal pain, and early satiety; additional ET symptoms are commonly vasomotor in nature and include headaches, dizziness, erythromelalgia, and concentration problems [1]. The MPN Landmark study demonstrated that these diseaserelated symptoms result in a reduced quality of life (QoL) in a majority of patients with MF and ET (81% and 57%, respectively) [7]. Notably, symptoms adversely affect patients’ QoL in not only those with the most severe disease, but also in those with low prognostic scores and in those in the lowest symptom
severity quartile [7].

Lower-risk patients with MF or ET have previously been reported to have a lower incidence of symptoms [10]; however, the severity and impact of MPN-associated symptoms is not well-recognized in lower-risk patients. Although treatments for both MF and ET are risk-adapted, and are directed at managing the disease and minimizing or improving symptoms [11,12], symptom burden is not included as a risk stratification factor for either MF or ET [12–15]. A practice of observation and monitoring of signs/symptoms for disease progression is recommended for lower-risk asymptomatic MF or low-risk ET [16,17]; however, patients with lower-risk symptomatic MF may receive cytoreductive therapy, ruxolitinib, or interferon at the physician’s discretion [17]. Therefore, characterizing symptom burden in these patients may help guide more effective disease management and treatment strategies.

Patient-reported outcome (PRO) instruments are validated questionnaires often used in observational studies and clinical trials to assess the effect of a treatment or condition from the patient’s perspective [18]. PRO instruments provide important and otherwise clinically difficult to obtain measures of the patient’s perception of their physical, social, and psychological wellbeing [19]. Although most PRO-based assessments
of patients with MF have focused on those with intermediate (INT) or higher risk disease, limited PRO data from patients with lower risk MF have been published. For example, the MPN Landmark study recruited patients with MPNs irrespective of risk category or treatment; of note, most recruited patients with MF had INT-2- or high-risk disease [7]. Therefore, although evidence exists for the effects of symptom burden on QoL in patients with INT-2 and high-risk MF, there are limited data describing the effects of symptom burden on QoL in patients with lower-risk MF. Similarly, little is known about the comparison of PROs in patients with high- versus low-risk ET, and the extent to which ET-directed treatment received relieves symptom burden in these patients. Despite the importance of assessing PROs, a review of a registry of clinical trials (initiated between 2006 and 2016) in patients with MPNs reported that only 19/35 reported on at least one PRO assessment as a study endpoint; of the 19 trials, only nine published a detailed analysis of PRO data [20]. Thus, there is an unmet need for further investigation into the extent to which symptom burden affects the daily lives and QoL of patients with lower risk MF and ET.

The Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST; NCT02953704) is an ongoing noninterventional study designed to collect clinical characteristics, PROs, and treatment patterns of patients with specific risk categories of clinically diagnosed MF and ET in community and academic centers throughout the United States. This analysis assessed patient-reported symptom burden and its effect on QoL, work productivity, and activity in patients with MF and ET at the time of enrollment in MOST.

Age-related macular degeneration and myeloproliferative neoplasms – A common pathway

Posted on October 11, 2022October 11, 2022 by mpn_admin

Charlotte Liisborg

First published: 06 October 2022

https://doi.org/10.1111/aos.15247

This thesis has been submitted to the Graduate School of Health and Medical Sciences, University of Copenhagen, Denmark – January 31, 2022.

English summary

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss and blindness in high-income countries. It is a progressive retinal disease leading to damage of the cells responsible for central vision. The early stages of the disease are often asymptomatic, while late-stage AMD, which is divided into two entities, neovascular AMD and geographic atrophy (GA), both show vision loss, though generally with different progression rates. Drusen and pigmentary abnormalities in the retina characterise early AMD, while nAMD and GA show angiogenesis in and atrophy of the retina, respectively. The aetiology is multifactorial and, in addition to ageing, which is the most significant risk factor for developing AMD, environmental- and genetic risk factors are implicated in the pathogenesis. Research has focused on local changes in the eye where inflammation has been found to play an essential role, but studies also point to systemic alterations and especially systemic inflammation to be involved in the pathogenesis.

The Philadelphia-negative myeloproliferative neoplasms (MPN) are a group of haematological cancers with an acquired genetic defect of the pluripotent haematopoietic stem cell, characterised by excess haematopoiesis of the myeloid cell lineage. The diseases have been found to evolve in a biological continuum from early cancer state, essential thrombocythemia, over polycythaemia vera (PV), to the advanced myelofibrosis stage (PMF). The symptoms in these patients are often a result of the changes in the blood composition, hyperviscosity, microvascular disturbances, and reduced tissue perfusion. The major causes of morbidity and mortality are thromboembolic- and haemorrhagic events, and leukemic transformation. A group of mutations that drive the MPNs has been identified, e.g., the JAK2V617F mutation, which results in deregulation of the JAK/STAT signal transduction pathway important, for instance, in cell differentiation and survival. A previous large register study has shown that patients with MPNs have an increased risk of neovascular AMD, and a pilot study has shown an increased prevalence of intermediate AMD. We wish to study this further in a larger scale study. Several studies have also shown that systemic inflammation plays an essential role in both the initiation and progression of the malignant cell clone in MPNs. From this knowledge, a “Human inflammation model” has been developed. Since then, the MPNs has been used as model diseases for a similar inflammation model for the development of Alzheimer’s disease. In this PhD project, we would like to investigate systemic inflammation in relation to drusen presence. We will do this by comparing systemic immunological markers previously investigated in patients with AMD and compare with MPN. We are primarily interested in systemic immunological differences between patients with MPN and drusen (MPNd) and MPN with normal retinas (MPNn).

This thesis consists of two main studies. Study I investigated the prevalence of retinal changes associated with AMD and the prevalence of different AMD stages in 200 patients with MPN (paper I). Study II examined immunological similarities between AMD and MPNs. This study was divided into three substudies exploring systemic markers of inflammation, ageing and angiogenesis, respectively. This was done in four types of patients: nAMD, intermediate AMD (iAMD), MPNd and MPNn. Investigating, differences between MPNd and MPNn, will make it possible to identify changes in the immune system, relevant for AMD pathogenesis. Additionally, we will compare patients with MPNs with patients with iAMD and nAMD.

In study I (Paper I), we found that patients with MPNs have a significantly higher prevalence of large drusen and consequently AMD from an earlier age compared to the estimates from three large population-based studies. We also found that drusen prevalence was associated with a higher neutrophil-to-lymphocyte ratio indicating a higher level of chronic low-grade inflammation in patients with drusen compared to those without drusen.

In study II (papers II, III and IV), we found immunological differences between patients with MPNd and MPNn. When we investigated markers of inflammation, we found a higher level of systemic inflammation in MPNd than MPNn. This was indicated by a higher inflammation score (based on levels of pro-inflammatory markers), a higher neutrophil-to-lymphocyte ratio, and indications of a deregulated complement system. When examining markers of ageing, we found signs of accelerated immune ageing in MPNd compared to MPNn, shown by more senescent effector memory T cells.

Finally, when exploring a marker of angiogenesis, we found a lower CXCR3 expression on monocytes and T cells in nAMD compared to iAMD, MPNd and MPNn, in line with previous studies of nAMD compared to healthy controls. Further, we found decreasing CXCR3 expression over the MPN biological continuum. These studies indicate CXCR3 involvement in both nAMD and PMF, two disease stages characterised by angiogenesis and fibrosis.

From the results of this PhD project, we can conclude that the prevalence of drusen and AMD is increased in patients with MPN compared to the general population. Further, our results show that systemic inflammation may play a far more essential role in AMD pathogenesis than previously anticipated. We, therefore, propose an AMD model (Figure 18) where inflammation can initiate and accelerate the normal age-dependent accumulation of debris in the retina, which later evolve into drusen, resulting in increased local inflammation, and over time early- and intermediate AMD. This results in the increased risk of developing the late debilitating stages of AMD.

Novel Interventions May Reduce Phlebotomy Use in Patients With Polycythemia Vera

Posted on October 11, 2022October 11, 2022 by mpn_admin

October 7, 2022

Brittany Lovely

Patients with polycythemia vera (PV), a myeloproliferative neoplasm associated with JAK2 mutations and overproduction of red blood cells, often require regular therapeutic phlebotomies to avoid thrombosis. The most common presentations of thrombosis in PV include stroke, myocardial infarction, peripheral arterial thrombosis, transient ischemic attack, peripheral vein thrombosis, pulmonary embolism, and thrombosis in unusual venous districts.¹

To achieve acceptable disease control, patients with low-risk disease may need to undergo phlebotomy up to 5 times per year, which can lead to adverse effects (AEs) such as iron deficiency. Those with high-risk disease require cytoreduction and correction of cardiovascular risk factors with or without phlebotomy.^1,2

Alternative interventional treatments to reduce the risk of thrombosis represent a significant unmet need in the community setting as phlebotomy and cytoreductive therapies including hydrea, ruxolitinib (Jakafi), and interferons have not demonstrated consistency in efficacy or tolerability.²

“Many patients who use pills, injections, [or] cytoreductive therapies, to minimize the need for phlebotomy. [However,] it seems that the achievement of the goal [to] control the hematocrit [levels] below 45% is not readily achieved in the community setting,” Srdan Verstovsek, MD, PhD, said in an interview with OncologyLive^®. “Many times, we considered PV a benign condition, [but] when you dig in and analyze the results it’s not so. Individuals are unnecessarily exposed to uncontrolled blood cell counts, which leads to untimely death from the thrombotic events. To optimize care in a community setting for patients with PV, we should all engage in developing new drugs.” Verstovsek is the United Energy Resources Inc, professor of medicine, director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, and chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston.

Assessing the Unmet Need for Patients with PV

“Most patients with PV will get at least 1 phlebotomy during the course of their treatment,” Aaron Gerds, MD, said in an interview with OncologyLive^®. “Even if they are going to [receive] alternative medication we may use phlebotomy early on to quickly get hematocrit down after diagnosis. Patients who are lower risk for thrombosis would be treated with phlebotomy alone and patients who are higher risk for thrombosis are treated with a medication, which can free them from the need for phlebotomy. But there are still a significant proportion of patients who require phlebotomy in addition to a medication to control counts. They’re really getting 2 treatments at once, which is complicated to manage, and can lead to multiple adverse effects.” Gerds is an assistant professor in medicine (hematology and medical oncology) at Cleveland Clinic Taussig Cancer Institute in Ohio.

A phase 3 study is underway to assess outcomes for patients with previously diagnosed PV who require phlebotomy on a regular basis. VERIFY (NCT05210790) will evaluate whether the addition of the novel hepcidin mimetic rusfertide to ongoing therapy for PV will eliminate the need for patients to receive or prolong time between phlebotomies.^2,3

“The phase 3 study is built on the experience from the phase 2 study [REVIVE; NCT04057040],” Verstovsek said. “It includes patients from a variety of backgrounds. They don’t necessarily need to be on any therapy at all, if they fulfill the requirement of too many phlebotomies, which is certainly harmful for them. The patients would come often at the beginning to make sure that they are [treated] optimally with rusfertide, [and determining the] optimal dose without the adverse effects [may] require a few months of adjustments. [There is planned] long-term follow-up, almost a year and more, because PV is a lifelong condition.”

Rusfertide works by suppressing PV erythropoiesis. “Basically, it tricks the bone marrow into thinking it’s already iron deficient when it isn’t, thus slowing down the production of red blood cells keeping the hematocrit under 45%,” Gerds explained.

REVIVE assessed the ability of rusfertide to maintain hematocrit levels below 45%. All patients underwent phlebotomy to achieve hematocrit below 45% prior to prior to the first dose of rusfertide dose. Seventy patients received rusfertide at a median dose of 40 to 60 mg weekly via self-administered subcutaneous dosing.

Among 63 evaluable patients, during the first 28 weeks of treatment, 84% of patients did not require a phlebotomy. Of those who did proceed to phlebotomy, 14% required 1 and 2% required 2 phlebotomies.2 Rusfertide demonstrated similar efficacy in all categories of patients, independent of the PV patient risk category or concurrent therapy with hydroxyurea, interferon or ruxolitinib. In terms of safety, the most common AE was injection site reaction (33%) but no patients discontinued because of injection site reactions.

“Here is a drug that is effective, it is safe, it is self-administered, it is therefore simple, and it appears to be durable,” Verstovsek said of the phase 2 data.

VERIFY Aims to Extend Phlebotomy-Free Intervals

The double-blind, placebo-controlled trial will evaluate patients with PV randomly assigned 1:1 to ongoing therapy with either rusfertide or placebo. The primary efficacy will be evaluated during weeks 20 to 32, with primary end analysis reported at week 32. At that time the study will be unblinded. Durability of response will be assessed between weeks 32 to 52; all enrolled patients then will proceed with their ongoing therapy and rusfertide.^2,3

At week 52, durability of response will be evaluated and patients will enter the long-term safety follow-up (weeks 52-156). Therapy administered during this portion of the trial will be PV therapy plus rusfertide. The end of treatment is week 156 with an additional safety follow-up period occurring for 4 weeks.^2,3

Verstovsek noted that the aim of the trial is not to eliminate disease but control it. “We want to prove that rusfertide is effective, safe, simple, and long lasting. Studies such as [VERIFY] that cover [approximately] 1 year are the norm for PV and we are looking forward to this study to be open across the globe over the next couple of years. [We want to demonstrate] the value of eliminating the need for phlebotomy, improving the quality of life for these patients, and having it on the market for our patients in every practice,” he said.

Taking the Patient into Consideration

Gerds noted that patients may also benefit from the elimination of the multiple burdens associated with phlebotomy. “It leads to iron deficiency and [individuals] can be symptomatic from the iron deficiency—they can experience tiredness, achiness, changes in hair and nails, and the most famous adverse effect of iron deficiency being pica, the urge to eat dirt or ice. Additionally, [phlebotomy] takes time,” Gerds said noting that the scheduling and repeat tests are a “logistical hassle.”

Self-administration of the agent is also a key differentiator for patients with PV. “Patients [administer] the shot at home. Thinking about a systems-based approach to delivering of care, an infusion or injection room chair [remains free] in your cancer center,” Gerds said.

He added that there are several barriers to overcome, most of which rely on patient education. “When prescribing a medication such as rusfertide, you also have to prescribe the syringes and the needles, and you have to teach the patient how to do the injections,” he said.

At Cleveland Clinic, Gerds noted that they provide educational videos and offer nursing visits. “We also need to instruct them to on how to care for the medication at home—do not store it in extreme temperatures, how to draw from the vial, etc,” Gerds said.

In June 2021, the FDA granted breakthrough therapy designation to rusfertide as a potential therapeutic option for patients with PV to reduce erythrocytosis in those who do not require further treatment for thrombocytosis and/or leukocytosis.⁴

“I would envision, if we are successful in proving the value in eliminating phlebotomy and improving quality of life, that rusfertide would be a natural choice for individuals who are otherwise low risk, manage with phlebotomy alone, and have problems with it,” Verstovsek said. “Rusfertide appears to fulfill the purpose in patients who are low risk and for patients who are receiving some other cytoreductive therapy [such as] hydroxyurea in suboptimal responders. Adding rusfertide to optimize the care eliminates the need for phlebotomy and is a natural next step. I think there is a possibility of multiple different clinical scenarios where the drug may become valuable for low-risk to high-risk patients.”

Gerds noted that next steps for building on this research is improving the concurrent medications administered for this patient population as well as the identification of prognostic biomarkers. “We always want to [achieve] deep remissions and have [patients] live much longer than we would anticipate. And the truth is patients with PV often do very well…but we lack a lot of good biomarkers.”

References

Vannucchi AM. How I treat polycythemia vera. Blood. 2014;124(22):3212-3220. doi:10.1182/blood-2014-07-551929
Hoffman R, Ginzburg Y, Kremyanskaya M, et al. Rusfertide (PTG300) treatment in phlebotomy-dependent polycythemia vera patients. J Clin Oncol. 2022;40(suppl 16):7003. doi:10.1200/ JCO.2022.40.16_suppl.7003
A phase 3 study of rusfertide in patients with polycythemia vera (VERIFY). ClinicalTrials.gov. Updated August 1, 2022. Accessed September 20, 2022. https://clinicaltrials.gov/ct2/show/ NCT05210790
Protagonist Therapeutics receives FDA breakthrough therapy designation for rusfertide in polycythemia vera. News release. Protagonist Therapeutics. June 3, 2021. Accessed September 20, 2022. bit.ly/3R0Tir8

Myelofibrosis Epidemiology Analysis and Forecast, 2021-2031

Posted on September 26, 2022September 26, 2022 by mpn_admin

ReportLinker

Thu, September 22, 2022 at 10:23 AM

Summary Myelofibrosis (MF) belongs to a group of diseases called myeloproliferative disorders. MF is a serious bone marrow disorder that disrupts the body’s normal production of blood cells (MedlinePlus, 2020; Mayo Clinic, 2021).

New York, Sept. 22, 2022 (GLOBE NEWSWIRE) — Reportlinker.com announces the release of the report “Myelofibrosis Epidemiology Analysis and Forecast, 2021-2031” – https://www.reportlinker.com/p06317718/?utm_source=GNW

MF includes primary MF (PMF), which is idiopathic. At times, essential thrombocytosis (ET) or polycythemia vera (PV) could progress to MF, resulting in post-essential thrombocytosis MF (PET MF) and post-polycythemia vera MF (PPV MF), which are referred to as secondary MF (SMF).

MF not only shortens survival but also severely compromises quality of life due to marked splenomegaly and profound constitutional symptoms including fatigue, night sweats, fever or uncomfortable feeling of warmth, weight loss, peripheral edema, pruritus, bone pain, dyspnea, and intractable cough (Mesa et al., 2009; Canadian Cancer Society, 2022).

In the 8MM, diagnosed incident cases of MF (sum of the diagnosed incident cases of PMF and SMF) are expected to increase from 12,276 cases in 2021 to 15,009 cases in 2031, at an Annual Growth Rate (AGR) of 2.23%. In 2031, China will have the highest number of diagnosed incident cases of MF in the 8MM, with 9,302 cases, whereas Spain will have the fewest diagnosed incident cases of MF with 413 cases. In the 8MM, the diagnosed prevalent cases of MF (sum of the diagnosed prevalent cases of PMF and SMF) are expected to increase from 69,236 cases in 2021 to 84,311 cases in 2031, at an AGR of 2.18%Epidemiologists attribute the increase in the diagnosed incident cases and diagnosed prevalent cases of MF to changes in the diagnosed incidence and survival rates, and population dynamics in each market.

Scope
– This report provides an overview of the risk factors, comorbidities, and the global and historical trends for MF in the eight major markets (8MM: US, France, Germany, Italy, Spain, UK, Japan, and China).
– It includes a 10-year epidemiological forecast for the diagnosed incident and diagnosed prevalent cases of MF, PMF, PET MF, and PPV MF based on county-specific studies published in peer-reviewed journals. The diagnosed incident cases of PMF are further segmented by sex, age (40-49 years, 50-59 years, 60-69 years, 70-79 years, and 80 years), the mutation-enhanced international prognostic scoring system (MIPSS70+) version 2.0 [very low risk (0 points), low risk (1-2 points), intermediate risk (3-4 points), high risk (5-8 points), and very high risk (?9 points)], mutations (JAK2V617F, CALR, and MPL), and anemia (with or without). The diagnosed prevalent cases of PMF are segmented by sex and age (40-49 years, 50-59 years, 60-69 years, 70-79 years, and 80 years). Epidemiologists also provide sex-specific diagnosed incidents and diagnosed prevalent cases of PET MF and PPV MF in the 8MM for the forecast period.

– The myelofibrosis epidemiology report is written and developed by Masters- and PhD-level epidemiologists.
– The Epidemiology Report is in-depth, high quality, transparent and market-driven, providing expert analysis of disease trends in the 8MM.

Read the full report here

How the Name Change to Myeloproliferative Neoplasms Affected People With the Disease

Posted on September 26, 2022September 26, 2022 by mpn_admin

September 23, 2022

Leah Lawrence

CURE, CURE Fall 2022, Volume 21, Issue 03

A decision to rename myeloproliferative neoplasms led to a plethora of developments in a space where there was once little interest.

To a greater extent, how would the evolution of the term myeloproliferative disorders (MPDs) — a group of diseases including polycythemia vera (PV), primary myelofibrosis (PMF) and essential thrombocythemia (ET) — to myeloproliferative neoplasms (MPNs) affect the lives of thousands upon thousands of people living with a rare disease?

As it turns out, that decision would transform the trajectory of a cancer space where there was once very little interest.

What’s in a Name?

In 2008, the World Health Organization (WHO) in collaboration with the United States-based Society for Hematopathology and the European Association for Haematopathology published a revised classification of the diseases that made up MPDs and officially classified them as neoplasms.

“They were considered a ‘disorder’ and then a ‘neoplasm,’” says David Ricci, a long-time member of the MPN Research Foundation Board of Directors. “The diseases had not changed. There was nothing about these diseases that was different before the change versus after the change.”

Instead, the change of name was made largely to be more accurate, Ricci

explains. The term MPDs dates back to a former president of the American Society of Hematology, Dr. Louis Wasserman, who coined the phrase to describe a range of diseases that had elevated blood counts, including chronic myeloid leukemia (CML), notes Dr. Ruben Mesa, executive director of Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center.

In PV, patients experience an increase in all blood cells, particularly red blood cells, which supply oxygen. Patients with ET have bone marrow that produces too many platelets, which can cause abnormal bleeding or blood clots. And in PMF, patients build up scar tissue in the bone marrow that produces blood cells, impairing the body’s ability to make normal blood cells.

“Over time we learned that all of these were neoplasms,” Mesa says. “All of the abnormal cells are related to one another, and that is a defining charac-teristic of a neoplasm.”

This characteristic is called clonality. Neoplasms are an abnormal growth of cells that can be either benign or malignant. MPNs start out as benign but may progress to being malignant.

“As science progressed and we learned this was a clonally driven disease, that sounded more like cancer,” says Dr. Michael R. Savona, head of hematology, cellular therapy and stem cell transplantation at Vanderbilt University Medical Center in Nashville, Tennessee.

“It would have been technically inaccu-rate to consider it otherwise.”

CTI BioPharma Announces Presentation of New Anemia Benefit Data from Pacritinib Program at the Society of Hematologic Oncology (SOHO) Tenth Annual Meeting

Posted on September 26, 2022September 26, 2022 by mpn_admin

SEATTLE, Sept. 21, 2022 /PRNewswire/ — CTI BioPharma Corp. (NASDAQ: CTIC) today announced two poster presentations from the Company’s pacritinib program at the Society of Hematologic Oncology (SOHO) Tenth Annual Meeting, to be held in Houston, Texas and virtually September 28 – October 1, 2022.

A new data analysis from the Phase 3 PERSIST-2 trial and an in vitro analysis of pacritinib, a novel JAK2/IRAK1 inhibitor approved by the U.S. FDA for patients with myelofibrosis and a platelet count below 50 x 10⁹/L, will highlight pacritinib’s impact on anemia and inhibition of Activin A receptor type 1 (ACVR1).

“Treatment with pacritinb at the approved dose of 200 mg twice daily (BID) led to improvements in transfusion independence and anemia when compared to best available therapy (BAT) in patients treated on the PERSIST-2 Phase 3 study,” said Dr. Stephen Oh, MD, PhD, Associate Professor of Medicine, Hematology Division at Washington University School of Medicine in St. Louis. “I am encouraged by these data, given the limited options to address anemia in myelofibrosis, especially high-risk patients with cytopenias who frequently require blood transfusions. I look forward to further investigation of pacritinib’s potential to alleviate anemia and related symptoms in this patient population.”

“We are pleased to report that pacritinib is a highly potent inhibitor of ACVR1. This inhibition is thought to lead to improvements in blood transfusion requirements and anemia in patients with cytopenic myelofibrosis,” said Adam Craig, MD, PhD, President and Chief Executive Officer of CTI BioPharma. “The data presented at SOHO 2022 support our belief that pacritinib is a simple, safe and effective JAK2 inhibitor. We plan to present additional data on pacritinib’s anemia benefit at a medical meeting later this year.”

A Patient Story: My Journey to a Better Life

Posted on September 1, 2022September 1, 2022 by mpn_admin

By Mayra D.

My Primary Myelofibrosis journey started on a festive Cinco de Mayo in 2015 while I was at work. Without any warning, I started to feel sick to the point that I almost collapsed at my desk. I still remember this incident like it was yesterday. I was sweating and had an awful pain in my lower back that kept me out of my chair. I had very severe discomfort in my upper abdomen that was not an ordinary stomach pain. At that moment I knew I was struggling health-wise. I was feeling so weak and so out of balance, things I had never felt or experienced before in my life. After this scary episode, I was rushed to the ER. When I got to the hospital, I was not able to walk, and breathing was very difficult. Even holding my cell phone was a challenge. I was admitted right away due to the fact that my hemoglobin was very low among other things. After a bunch of blood transfusions, IV treatments, and everything in between, the doctors were able to stabilize my condition. After a week I was released from the hospital and started what I called ‘My Health Crisis Path’.

I started to see an Oncologist/Hematologist on a regular basis. One year later, I was rushed to the ER once again. At first the doctors thought I was pre-menopausal and that was the cause of the anemia. No, it wasn’t! The severe night sweats, the awful skin itching, especially after taking a shower, the painful feet, and leg cramps at night while in bed, and the severe anemia, were all part of a few of the new symptoms I was experiencing. Overall, my health was not improving, and I was feeling weaker every day. After a year and a half of trying new treatments with no diagnosis, the Oncologist/Hematologist team decided that the next step for me was a bone marrow biopsy. Everything became crystal clear with my ‘Jak 2 Mutation’ and the finding of Primary Myelofibrosis (MF).

This health crisis of mine impacted me and my entire family. My husband got so overwhelmed he even lost his job. I was forced to resign from my job and my husband losing his caused a great struggle financially. It was okay, and we managed together as a family, but having him by my side every step of the way was more important and something money can’t buy.

On the other hand, my daughter, who was only 14, felt like she was losing her mom. She reached rock bottom not only emotionally but academically. Today I can say joyfully my daughter is now 21 years old and is a successful college student attending a State University. Through all of this, we saw a psychiatrist and had a few counseling sessions in order to help us individually and as a family cope with this unexpected health crisis. It has helped us with the healing and moving forward process. Our daughter once said: “We are a family no one left behind.”

I used to donate blood and today I am on the other side of the chair. My driver’s license even says that I am an organ donor. Slowly but surely, I started to accept the fact that I suffered from a rare chronic blood disorder. I had two options in front of me, either feel sorry for myself and do nothing about it or go out there and make a difference. I chose the second option. It was not an easy task. In the beginning, I felt alone and confused, and I didn’t know where to go for help, support, and answers. When I heard the word ‘cancer’ for the first time it was a feeling I can’t explain. But this didn’t stop me.

Being a former graphic designer, I was used to putting on a creative hat, so I knew what to do next. I began by researching about MPN in general. In the process, I came up with what I called ‘My 4 Daily Elements’: Chemo-Tablet Treatment, Anti-Inflammatory Nutritional Meal Plan, Routine of Exercise, and Mindfulness (I want to point out that when I started this health journey there was not much guidance like there is today). A few years ago, I received a couple of certificates in Modeling and Acting from a local school, so I decided to take advantage and use these tools. This knowledge and experience are my platform for cancer awareness. Today I’m proud to say I’m a member of a Cancer Support Community at the cancer institute in Orlando, FL. I’m also a member of MPN groups on social media. I was interviewed a couple of years ago and an article of my journey was published in Prevention Magazine. What an honor it was being able to speak about this rare and chronic blood disorder. We may be a small group, but our voices can make a big difference.

I am also the voice in the Latino community. I spoke on a local radio station where I was able to bring awareness to Central Florida. In my message I let the listeners understand that talking about cancer doesn’t make you a victim or a weak person, it makes us stronger by informing others. I even asked one of the CSC-Mental Health Therapist to join me for another live radio chat so we could talk about integrative medicine and what it offers the cancer community.

Next month, I’m going to attend my first meeting as part of the Patient and Family Advisory Council at Orlando Health. In December I’m also going to be participating in the Sea World 3 Mile Reindeer Run for pediatric cancer and bone marrow transplant programs at AdventHealth for the second year. Sharing my story is very important to me. If I can shed light, hope, and support to others then my mission is accomplished. “ME with a Purpose.”

Incyte Announces FDA Approval Of Pemazyre® (Pemigatinib) As The First And Only Targeted Treatment For Myeloid/Lymphoid Neoplasms (MLNs) With FGFR1 Rearrangement

Posted on August 29, 2022August 29, 2022 by mpn_admin

August 26, 2022 at 10:00am EDT

– This marks the second indication for Pemazyre, which received accelerated FDA approval in 2020 for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement

– Pemazyre is the only FGFR inhibitor with multiple indications

WILMINGTON, Del.–(BUSINESS WIRE)–Aug. 26, 2022– Incyte (Nasdaq:INCY) today announced that the U.S. Food and Drug Administration (FDA) has approved Pemazyre^® (pemigatinib), a selective fibroblast growth factor receptor (FGFR) inhibitor, for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. MLNs with FGFR1 rearrangement are extremely rare and aggressive blood cancers that may impact less than 1 in 100,000 people in the United States¹.

“The approval of Pemazyre represents an important treatment advancement for people living with MLNs with FGFR1 rearrangement who currently have limited treatment options,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “These are complex hematologic malignancies with a range of presentations, and this approval highlights Incyte’s continued leadership and commitment to advancing care for patients with rare blood cancers.”

A patient with an MLN with FGFR1 rearrangement may present with bone marrow involvement with a chronic myeloid malignancy (such as myeloproliferative neoplasm [MPN], myelodysplastic syndrome/MPN) or a blast phase malignancy (such as B- or T-cell acute lymphoblastic leukemia/lymphoma, acute myeloid leukemia or mixed phenotype acute leukemia). Bone marrow involvement may or may not be accompanied by extramedullary disease (EMD); some patients may present with EMD only. MLNs with FGFR1 rearrangement are caused by chromosomal translocations involving the FGFR1 gene, with various partner genes resulting in constitutive activation of the FGFR1 receptor tyrosine kinase, impacting cell differentiation, proliferation and survival². Patients often relapse because existing first-line therapies sometimes fail to induce durable clinical and cytogenetic responses.

The FDA approval was based on data from the Phase 2 FIGHT-203 study, a multicenter open-label, single-arm trial that evaluated the safety and efficacy of Pemazyre in 28 patients with relapsed or refractory MLNs with FGFR1 rearrangement. Patients could have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or after a disease modifying therapy or were not a candidate for allo-HSCT or other disease modifying therapies.

Study participants included patients with documented MLNs with an 8p11 translocation on conventional cytogenetics and/or an FGFR1 rearrangement on break-apart FISH testing. (An FDA-approved test for detection of FGFR1 rearrangement in patients with relapsed or refractory MLNs is not available.)
In patients with chronic phase in the marrow with or without EMD (N = 18), the complete response (CR) rate was 78% (14/18; 95% CI 52, 94). The median time to response of CR was 104 days (range, 44 to 435 days). The median duration of CR was not reached (range, 1+ to 988+ days).
In patients with blast phase in the marrow with or without EMD (N = 4), two patients achieved a CR (duration: 1+ and 94 days).
In patients with EMD only (N = 3), one patient achieved a CR (duration: 64+ days).
For all patients (N = 28 including three patients without evidence of morphologic disease) the complete cytogenetic response rate was 79% (22/28; 95% CI: 59, 92).

The most common (≥ 20%) adverse reactions were hyperphosphatemia (74%), nail toxicity (62%), alopecia (59%), stomatitis (53%), diarrhea (50%), dry eye (50%), fatigue (44%), rash (35%), abdominal pain (35%), anemia (35%), constipation (32%), dry mouth (32%), epistaxis (29%), retinal pigment epithelial detachment (26%), extremity pain (26%), decreased appetite (24%), dry skin (24%), dyspepsia (24%), back pain (24%), nausea (21%), blurred vision (21%), peripheral edema (21%) and dizziness (21%).

“In patients with relapsed or refractory MLNs with FGFR1 rearrangement treated with Pemazyre in FIGHT-203, the high rate of complete response and complete cytogenetic response in patients with chronic phase disease and the high rate of complete cytogenetic response in patients with blast phase disease is clinically meaningful, especially in light of the lack of these specific responses with existing first-line treatments,” said Dr. Srdan Verstovsek, M.D., Ph.D., Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, and principal investigator for the FIGHT-203 study.

The supplemental New Drug Application (sNDA) for Pemazyre for the treatment of adults with relapsed or refractory MLNs with FGFR1 rearrangement was reviewed by the FDA under Priority Review. The FDA grants Priority Review to medicines that may offer a major advance in treatment where none currently exists. The designation shortens the review period to six months compared to 10 months for Standard Review.

Incyte established its leadership in rare blood cancers more than 10 years ago with the development of the first JAK inhibitor approved by the FDA for the treatment of certain patients with myelofibrosis and polycythemia vera. Incyte continues to research additional pathways to address rare blood cancers through its LIMBER (Leadership In MPNs Beyond Ruxolitinib) clinical development program, designed to evaluate multiple therapies and investigational strategies to improve and expand treatments for patients living with MPNs and other related hematologic malignancies and conditions.

Incyte is committed to supporting patients and removing barriers to access medicines. Eligible patients in the U.S. who are prescribed Pemazyre have access to IncyteCARES (Connecting to Access, Reimbursement, Education and Support), a comprehensive program offering personalized patient support, including financial assistance and ongoing education and additional resources. More information about IncyteCARES is available by visiting www.incytecares.com or calling 1-855-452-5234.

About FIGHT-203
FIGHT-203 is a Phase 2, multicenter trial that enrolled patients 18 years and older with myeloid/lymphoid neoplasms (MLNs) with a fibroblast growth factor receptor 1 (FGFR1) rearrangement. Sponsored by Incyte, the study evaluated the safety and efficacy of pemigatinib for the treatment of adults with MLNs with FGFR1 rearrangement. Patients received pemigatinib 13.5 mg once daily in 21-day cycles, either on a continuous schedule (the approved recommended starting dosage for use in patients with MLNs with FGFR1 rearrangement) or as an intermittent schedule (14 days on, 7 days off, an unapproved dosage regimen in MLN with FGFR1 rearrangement). Pemigatinib was administered until disease progression or unacceptable toxicity or until patients were able to receive allo-HSCT. For more information about the study, please visit https://clinicaltrials.gov/ct2/show/NCT03011372.

About Pemazyre^® (pemigatinib)
Pemazyre, a fibroblast growth factor receptor (FGFR) inhibitor, is the first targeted treatment approved for use in the United States for treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement.

Pemazyre is also indicated for the treatment of adults with relapsed or refractory previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement as detected by an FDA-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response (DOR). Continued approval may be contingent on verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Ocular Toxicity
Retinal Pigment Epithelial Detachment (RPED): PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring including optical coherence tomography (OCT) to detect asymptomatic RPED; therefore, the incidence of asymptomatic RPED with PEMAZYRE is unknown.

Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%. The median time to first onset of RPED was 56 days. RPED led to dose interruption of PEMAZYRE in 3.1% of patients, and dose reduction and permanent discontinuation in 1.3% and in 0.2% of patients, respectively. RPED resolved or improved to Grade 1 levels in 76% of patients who required dosage modification of PEMAZYRE for RPED.

Perform a comprehensive ophthalmological examination including OCT prior to initiation of PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during treatment. For onset of visual symptoms, refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE. Modify the dose or permanently discontinue PEMAZYRE as recommended in the prescribing information for PEMAZYRE.

Dry Eye: Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, dry eye occurred in 31% of patients, including Grade 3-4 in 1.6% of patients. Treat patients with ocular demulcents as needed.

Hyperphosphatemia and Soft Tissue Mineralization
PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, hyperphosphatemia was reported in 93% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169). Phosphate lowering therapy was required in 33% of patients receiving PEMAZYRE.

Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is >5.5 mg/dL. For serum phosphate levels >7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia as recommended in the prescribing information.

Embryo-Fetal Toxicity
Based on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm when administered to a pregnant woman. Oral administration of pemigatinib to pregnant rats during the period of organogenesis caused fetal malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 13.5 mg.

Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose.

Adverse Reactions: Cholangiocarcinoma
Serious adverse reactions occurred in 45% of patients receiving PEMAZYRE (n=146). Serious adverse reactions in ≥2% of patients who received PEMAZYRE included abdominal pain, pyrexia, cholangitis, pleural effusion, acute kidney injury, cholangitis infective, failure to thrive, hypercalcemia, hyponatremia, small intestinal obstruction, and urinary tract infection. Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion.

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received PEMAZYRE. Adverse reactions requiring permanent discontinuation in ≥1% of patients included intestinal obstruction and acute kidney injury.

Dosage interruptions due to an adverse reaction occurred in 43% of patients who received PEMAZYRE. Adverse reactions requiring dosage interruption in ≥1% of patients included stomatitis, palmar-plantar erythrodysesthesia syndrome, arthralgia, fatigue, abdominal pain, AST increased, asthenia, pyrexia, ALT increased, cholangitis, small intestinal obstruction, alkaline phosphatase increased, diarrhea, hyperbilirubinemia, electrocardiogram QT prolonged, decreased appetite, dehydration, hypercalcemia, hyperphosphatemia, hypophosphatemia, back pain, pain in extremity, syncope, acute kidney injury, onychomadesis, and hypotension.

Dose reductions due to an adverse reaction occurred in 14% of patients who received PEMAZYRE. Adverse reactions requiring dosage reductions in ≥1% of patients who received PEMAZYRE included stomatitis, arthralgia, palmar-plantar erythrodysesthesia syndrome, asthenia, and onychomadesis.

Clinically relevant adverse reactions occurring in ≤10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 0.5% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N = 635]). Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated with hyperphosphatemia were observed with PEMAZYRE treatment.

Within the first 21-day cycle of PEMAZYRE dosing, serum creatinine increased (mean increase of 0.2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

In cholangiocarcinoma (n=146) the most common adverse reactions (incidence ≥20%) were hyperphosphatemia (60%), alopecia (49%), diarrhea (47%), nail toxicity (43%), fatigue (42%), dysgeusia (40%), nausea (40%), constipation (35%), stomatitis (35%), dry eye (35%), dry mouth (34%), decreased appetite (33%), vomiting (27%), arthralgia (25%), abdominal pain (23%), hypophosphatemia (23%), back pain (20%), and dry skin (20%).

Adverse Reactions: Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement

Serious adverse reactions occurred in 53% of patients receiving PEMAZYRE at all dosages (n=34). Serious adverse reactions in > 5% of patients included acute kidney injury. Fatal adverse reactions occurred in 9% of patients who received PEMAZYRE, including acute kidney injury, multiple organ dysfunction syndrome, and malignant neoplasm progression, occurring in one patient each.

Permanent discontinuation due to an adverse reaction occurred in 12% of patients who received PEMAZYRE at all dosages. Adverse reactions requiring permanent discontinuation included cardiac failure, multiple organ dysfunction syndrome, blood alkaline phosphatase increase, and calciphylaxis. In patients who started treatment on the recommended dosage (n = 20), adverse reactions requiring dosage interruption of PEMAZYRE occurred in 80% of patients. Adverse reactions which required dosage interruption in > 2 patients treated at the recommended dosage included nail toxicities (20%) and hyperphosphatemia (15%).

Dose reductions of PEMAZYRE due to an adverse reaction occurred in 80% of patients who started treatment on the recommended dosage. Adverse reactions requiring dose reductions occurring in > 2 patients were nail toxicities (20%), hyperphosphatemia (20%), and alopecia (15%).

Drug Interactions

Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce the dose of PEMAZYRE if concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE.

Special Populations
Advise lactating women not to breastfeed during treatment with PEMAZYRE and for 1 week after the last dose.

Reduce the recommended dose of PEMAZYRE for patients with severe renal impairment as described in the prescribing information.

Reduce the recommended dose of PEMAZYRE for patients with severe hepatic impairment as described in the prescribing information.

Please see Full Prescribing Information for PEMAZYRE.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

You may also report side effects to Incyte Medical Information at 1-855-463-3463.