Cellenkos Announces First Patient Dosed with CK0804 Cell Therapy in LIMBER-TREG108 Clinical Trial

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Category: DNA RNA and Cells

Published on Saturday, 07 January 2023 18:23

  • First patient dosed with CK0804 Treg cells as an add on therapy to ruxolitinib in patients with myelofibrosis who experience a suboptimal response to ruxolitinib.
  • On-going Phase 1b study evaluating safety of CK0804

HOUSTON, TX, USA I January 06, 2023 I Cellenkos Inc, a clinical stage biotechnology company focused on the development of allogeneic, off-the-shelf, T regulatory cell therapies targeting inflammatory disorders and autoimmune diseases, today announced that the first patient was dosed in the Phase 1b LIMBER-TREG108 study evaluating CK0804 as an add on therapy to ruxolitinib in patients with myelofibrosis who experience a suboptimal response to ruxolitinib. CK0804 is a novel allogeneic, CXCR4 enriched, T regulatory cell therapy product that utilizes Cellenkos’ proprietary CRANE™ technology to generate disease specific products.

The LIMBER-TREG108 trial (NCT05423691) is part of a development collaboration between Cellenkos and Incyte.

“This is an exciting milestone for our company. The initiation of this study of CK0804 as on add on therapy to ruxolitinib is an important achievement that brings us closer to delivering a potential new treatment which may have a life-changing impact for myelofibrosis patients who have less than optimal response to treatment with ruxolitinib,” said Tara Sadeghi, Chief Operating Officer of Cellenkos Inc., “Myelofibrosis patients who do not respond to ruxolitinib have limited treatment options and can progress to leukemia. This experimental immunotherapy treatment in combination with the standard of care may represent a new hope for the patients with myelofibrosis potentially enhancing the efficacy of current JAK inhibitor therapy while also offering possible immune modulation and restoration of impacted hematopoiesis.”

LIMBER-TREG108 is a multicenter study at The University of Texas MD Anderson Cancer Center, The University of Columbia Hospital and University of California, Davis. The study is led by principal investigator Lucia Masarova, M.D., Assistant Professor of Leukemia at MD Anderson. This Phase 1b study will evaluate the safety, pharmacodynamics and immunogenicity of intravenous CK0804, administered monthly for up to 6 doses. The study will consist of 2 phases: an open-label safety run-in of 9 patients (Stage 1) and an expansion cohort of 15 additional patients (Stage 2).

“We are pleased that the first patient first dose milestone in the LIMBER-TREG108 study – one of several studies in our LIMBER clinical program evaluating multiple monotherapy and combination strategies to improve and expand treatments for patients with MPNs – has been achieved. We look forward to the results of the study, and to continuing our partnership toward important scientific advances for these patients,” said Ekaterine Asatiani, M.D., Division Vice President and Head of Early Development at Incyte.

About Myelofibrosis

Myelofibrosis is a rare, chronic and progressive blood cancer that is part of a group of diseases known as myeloproliferative neoplasms. In myelofibrosis, scar tissue forms in the bone marrow and impairs its ability to produce normal blood cells. This can result in an enlarged spleen, as well as symptoms such as fatigue, itching and night sweats, which can severely impact a patient’s quality of life. About 16,000 to 18,500 people in the U.S. are living with myelofibrosis1. Patients who have had a suboptimal response to the standard of care treatment have limited options and a poor prognosis.

About CK0804

CK0804 is a novel allogenic cell therapy product consisting of T-regulatory cells that exploit the CXCR4/CXCL12 axis and are derived from clinical-grade umbilical cord blood units and manufactured using Cellenkos’ proprietary CRANE™ process. Multiple doses of CK0804 can be manufactured from a single umbilical cord blood unit, where the final cryopreserved product is readily available for use. No requirement for HLA matching to the patients makes CK0804 an ideal therapy that can be infused intravenously, in the outpatient setting.

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Global Myeloproliferative Disorders Drugs Market to Reach $11.2 Billion by 2027

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ReportLinker
ReportLinker
·24 min read
In the changed post COVID-19 business landscape, the global market for Myeloproliferative Disorders Drugs estimated at US$8. 5 Billion in the year 2020, is projected to reach a revised size of US$11.

New York, Dec. 28, 2022 (GLOBE NEWSWIRE) — Reportlinker.com announces the release of the report “Global Myeloproliferative Disorders Drugs Industry” – https://www.reportlinker.com/p06032290/?utm_source=GNW
2 Billion by 2027, growing at aCAGR of 3.9% over the period 2020-2027. Ph+ Chronic myelogenous leukemia (CML), one of the segments analyzed in the report, is projected to record 3.4% CAGR and reach US$8.1 Billion by the end of the analysis period. Taking into account the ongoing post pandemic recovery, growth in the Ph- Myeloproliferative Neoplasms (MPNs) segment is readjusted to a revised 5.5% CAGR for the next 7-year period.

The U.S. Market is Estimated at $2.3 Billion, While China is Forecast to Grow at 6.4% CAGR

The Myeloproliferative Disorders Drugs market in the U.S. is estimated at US$2.3 Billion in the year 2020. China, the world`s second largest economy, is forecast to reach a projected market size of US$2.2 Billion by the year 2027 trailing a CAGR of 6.4% over the analysis period 2020 to 2027. Among the other noteworthy geographic markets are Japan and Canada, each forecast to grow at 2.3% and 3.1% respectively over the 2020-2027 period. Within Europe, Germany is forecast to grow at approximately 2.8% CAGR.

Select Competitors (Total 34 Featured) –
Bristol-Myers Squibb
Inctye
Novartis
Pfizer
Takeda
Teva

Read the full report: https://www.reportlinker.com/p06032290/?utm_source=GNW

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Overview of Treatment Options for Myelofibrosis

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Rami S. Komrokji, M.D., Ruben Mesa, M.D.

Transcript:

Rami Komrokji, M.D.: I think ET (essential thrombocythemia) and PV (polycythemia vera) are similar but myelofibrosis probably is a little bit different, so the spectrum of symptoms and the goals of treatment may be different. I’ll ask you to walk us through how you think of managing myelofibrosis patients.

 

Ruben Mesa, M.D.: Well, I think that’s very helpful, Rami. I think that was a great description of how we treat ET and PV. Again, we’re trying to use a range of therapies, and we’ll discuss a little later some of the newer therapies. What I do is kind of early MPNs (myeloproliferative neoplasms), and not every patient leaves as an early MPN patient based on risk of blood clots, bleeding, potential symptoms, but they can progress to myelofibrosis. As we mentioned earlier, myelofibrosis in our spleen, difficult symptoms and sometimes lower blood counts has some variable risk of progression to acute leukemia. Now, MF (myelofibrosis) patients can have evolved from ET or PV. Again, as we’re monitoring those diseases, if they start to change, such as a bigger spleen, worsening symptoms, lower blood counts or scarring in the bone marrow, and we think they’ve progressed from MF or they’ve started it, we call it primary myelofibrosis. Now, when we consider treating MF, we do treat it differently than ET or PV, because it has the potential to be life-shortening. Now, it’s not life-shortening in everyone. Our therapies are helping to extend life. Individuals might be diagnosed (at older ages) and they may die of something else, but it does have that potential. Because of that, the first decision we (consider) as your physicians and you as a patient is “Should we pursue a bone marrow transplant?” Bone marrow transplant, it’s synonymous with stem cell transplant, can cure myelofibrosis. However, it’s a very complex therapy. It’s probably one of the most complex medical therapies an individual can undergo. Even in the best of circumstances, there is a real risk that the transplant could potentially be a life-threatening complication. Who do we transplant? We consider that in individuals, the younger you are, the more aggressive we think your myelofibrosis might be. The more fit you are, and the more aggressive you wish to be with your health care, the more we consider it. We will consider it (in ages up to) the late 70s, but as we get older, the risks become higher and the likelihood of it being a good option is lower. That’s a discussion and a thought process that occurs usually in parallel with us deciding on treatment. For treatment, we again consider the risks and benefits and stratify patients accordingly. First, there are low-risk patients who have no symptoms. There’s an occasion when we find someone who came in for a general physical and the spleen was enlarged, and we finally find myelofibrosis, but otherwise, they wouldn’t know they were sick. This is a minority. In these individuals, sometimes we will watch the disease. That is still a small minority of patients. People who have more risk than that and more symptoms, we typically will start on a medicine. Now we have three approved medicines. By far the one that has been used the greatest up to this point because it’s been approved now over 10 years is ruxolitinib. This is a medicine, a pill, that’s given twice a day, and it was approved because of the benefit it had for patients with MF, such as improving enlargement of the spleen. Sometimes the spleen can be under the rib cage on the left side, and sometimes it can be many times larger than it should be. It can cause discomfort, fullness and pain, and because of that, we like to reduce it. It can help with symptoms, and it can even impact the course of the disease; ruxolitinib clearly can have that benefit. It can improve symptoms, help you gain weight and help to improve the other symptoms such as fatigue, night sweats and so on. It likely helps patients with myelofibrosis live longer, and perhaps, in some individuals, even significantly longer than they would have lived otherwise. We know you can take it for a long time. I saw a patient yesterday in-clinic who first went on ruxolitinib in 2009 and has been on it ever since then. That’s dramatically longer than we might have expected that individual to live. It’s really made a big impact. Now, it has limitations. It sometimes can cause anemia, increase the risk of skin cancers and increase the risk of some infections, but it’s a good therapy. Second, we have fedratinib, which was approved much more recently in 2019. It can be helpful like ruxolitinib. It sometimes can be helpful to give if ruxolitinib initially didn’t help. It also can cause anemia, diarrhea or nausea. We usually give medicines for that. It rarely can lower vitamin B1 in the blood, which can cause something called encephalopathy, so we monitor for that. Usually, monitoring for that and giving vitamin B1 helps to nip that in the bud. The third medicine approved much more recently is for the subset of patients with myelofibrosis who have a very low platelet count that increases their risk of bleeding. Ruxolitinib and fedratinib can lower the platelet count, so the having pacritinib is a big plus. We can give it at full dose. We can have benefits for the spleen or for symptoms in individuals with a low platelet count. There are these three options, and some more are on the way. We’ll talk about some of the therapies on the way in a moment.

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Dr. Oh on the Anemia Benefit of Pacritinib in Myelofibrosis

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Dec 22, 2022

By Stephen Oh, MD, PhD

Stephen T. Oh, MD, PhD, co-chief, Division of Hematology, associate professor, Department of Medicine, Hematology Division, associate professor, Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, discusses the anemia benefit of pacritinib (Vonjo) in patients with myelofibrosis.

The phase 3 PERSIST-2 study (NCT02055781) evaluated the safety and efficacy of oral pacritinib compared with best available therapy in patients with thrombocytopenia and primary or secondary myelofibrosis. At the 2022 ASH Annual Meeting, investigators presented an analysis of pacritinib as a potent ACVR1 inhibitor and its clinical impact on transfusion independence in patients with myelofibrosis.

Although pacritinib is approved by the FDA for the treatment of adult patients with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L, data from the analysis showed that the agent provides an anemia benefit for other patients with myelofibrosis, Oh says.

Pacritinib displayed activity as an inhibitor of ACVR1 and reduced hepcidin levels in vitro. Treatment with the agent can lead to transfusion independence for patients with myelofibrosis who require red blood cell transfusions. These data, along with the efficacy findings from PERSIST-2, should be taken into consideration for deciding considering pacritinib, Oh concludes.

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Top Researcher Mesa to Lead Atrium Health Cancer Program

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December 13, 2022

CHARLOTTE– Dr. Ruben A. Mesa has been named president and executive director of Atrium Health’s cancer service line – which includes Atrium Health Levine Cancer Institute and Atrium Health Wake Forest Baptist Comprehensive Cancer Center – and vice dean for cancer programs at Wake Forest University School of Medicine.

Mesa will assume the roles filled by Dr. Derek Raghavan, who had previously announced his mid-January 2023 retirement and by Dr. William Blackstock, professor and chair of radiation oncology at Wake Forest University School of Medicine, who has served as interim director of Wake Forest Baptist’s Comprehensive Cancer Center since February.

Mesa will advance the growth and development of the health system’s cancer center and the entire cancer service line. He will be responsible for all aspects of the cancer program, including clinical operations, research, education, community outreach and diversity, equity and inclusion.

“Dr. Mesa is a nationally renowned researcher, academic and oncology expert who has been at the forefront of cutting-edge advancement for cancer prevention, screening and treatment across the country,” said Eugene A. Woods, CEO of Advocate Health, of which Atrium Health is a part. “Most importantly, he has a patient-first philosophy and will be the chief advocate leading the charge in the battle against cancer.”

Mesa serves as executive director of the Mays Cancer Center at UT Health San Antonio MD Anderson and professor of medicine at UT Health Science Center San Antonio. He has dedicated his career to research and drug development for myeloproliferative neoplasms – a group of chronic leukemias that can cause bone marrow problems, acute leukemia and premature death.

Over the past 11 years, Mesa has led or co-led the development of six drugs that have been FDA-approved for chronic leukemias. He has been the principal investigator or co-principal investigator for more than 100 cancer clinical trials, including numerous global Phase III trials.

Mesa’s accomplishments during his tenure at UT Health San Antonio include leading the planning and design of a new research specialty hospital to focus on cancer, integrating cancer prevention and screening practice and research activities, and expanding oversight for Greehey Children’s Cancer Research Institute – one of only two institutes in the country dedicated solely to pediatric cancer research.

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MPN Research Foundation Awards Additional $1.8 Million for Blood Cancer Research Into Myeloproliferative Neoplasms

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CHICAGO, IL, UNITED STATES, December 14, 2022 /EINPresswire.com/ — MPN Research Foundation (MPNRF) announces its 2022 Thrive Initiative recipients for projects that fill research funding gaps, some of which surfaced due to the pandemic. This $1.8 million in awards is in addition to currently funded research projects supported for 2021-2023.

MPNRF has invested more than $18.4 million over the past 21 years toward better understanding and treatment of essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), rare blood cancers collectively known as myeloproliferative neoplasms (MPNs).

“The 2022 Thrive Initiative will fund 11 additional MPN research projects totaling $1.8 million over two years,” according to Kapila Viges, MPNRF chief executive officer. “These include an exciting mix of seasoned MPN researchers, awarded for follow-on support to continue their existing projects, in many cases stalled by the pandemic, as well as junior and established investigators with new ideas and perspectives to explore. Together, they bring new talent and energy to solve compelling MPN questions, pioneering the way for new research and treatments.”

“We are thrilled to fund so many new or incomplete projects that otherwise might be left on the research bench without support,” says Brandon Goetzman, MPNRF board member and chair of the Scientific Steering Committee. “Each project went through a rigorous peer review process, with final selections based on scientific merit, independent of research focus.“

 

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Incyte’s Novel Mutant CALR Antibody Unveiled at ASH 2022 Plenary Scientific Session

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– INCA033989, a new anti-mutant calreticulin (CALR)-targeted monoclonal antibody, represents important research milestone in myelofibrosis (MF) and essential thrombocythemia (ET)

– INCA033989 abstract selected as one of only six ASH plenary presentations

– INCA033989 clinical trials to begin in 2023

– Research highlights Incyte’s discovery capabilities and progress of its LIMBER program evaluating new targets and combinations for patients with myeloproliferative neoplasms (MPNs) and graft-versus-host disease (GVHD)

WILMINGTON, Del.–(BUSINESS WIRE)–Incyte (Nasdaq:INCY) today announced new research detailing the development and mechanism of action of INCA033989, an Incyte-discovered, investigational novel anti-mutant calreticulin (CALR)-targeted monoclonal antibody. Pre-clinical data indicate that INCA033989 can alter disease course by reducing mutant CALR allele burden and thus may be an efficacious and safe treatment in patients with myelofibrosis (MF) and essential thrombocythemia (ET). This research was featured in the Plenary Scientific Session (Abstract #6. Session: Hematology Disease Topics & Pathways: Research, Diseases, Therapies, Myeloid Malignancies) at the 64th American Society of Hematology (ASH) Annual Meeting, held December 10-13, 2022, in New Orleans and virtually1.

“As a leader in the field, Incyte is uniquely positioned to develop novel medicines for these rare blood cancers, and this research provides strong rationale for the continued investigation and clinical advancement of INCA033989 – a novel treatment approach that targets CALR mutations.”

“As a pioneer in the field of myeloproliferative neoplasms (MPNs), having brought the first FDA-approved treatment to patients, we are excited to have the opportunity to share details of our latest research,” said Dash Dhanak, Ph.D., Executive Vice President and Chief Scientific Officer, Incyte. “We continue to apply our deep understanding of the complex biology of MPNs to expand treatment options for patients and the work on INCA033989 presented today reflects our progress toward this goal. We look forward to continuing to advance the development of this potential new treatment and to initiating clinical trials for INCA033989 next year.”

CALR mutations are responsible for disease development in approximately 25-35%2,3 of patients with MF and ET – two common types of MPNs. INCA033989 binds with high affinity to mutant CALR and inhibits oncogenesis, the process of cells becoming cancerous, in cells expressing this oncoprotein. As described in our presentation, INCA033989 potently antagonizes CALR oncogenic function, resulting in selective inhibition of JAK/STAT signaling only in CALR-mutated cells with no effect on normal, non-oncogenic cells. This selectivity of action with INCA033989 results in the specific killing of tumor cells harboring the mutation and is suggestive of the potential to alter the course of disease in patients with CALR-mutant MF and ET.

“Diseases like myelofibrosis and essential thrombocythemia are often difficult to understand and treat, and unique approaches are necessary to develop effective and safe therapies,” said Srdan Verstovsek, M.D., Ph.D., Professor of Medicine, Department of Leukemia, University of Texas MD Anderson Cancer Center. “As a leader in the field, Incyte is uniquely positioned to develop novel medicines for these rare blood cancers, and this research provides strong rationale for the continued investigation and clinical advancement of INCA033989 – a novel treatment approach that targets CALR mutations.”

More information regarding the congress and the more than 50 abstracts from Incyte’s oncology portfolio being featured at the meeting is available on the ASH website: https://www.hematology.org/meetings/annual-meeting.

About Myeloproliferative Neoplasms

Myeloproliferative neoplasms (MPNs) are a closely related group of blood cancers in which the bone marrow functions abnormally. The bone marrow is where the body’s blood cells are made. MPNs are progressive blood cancers that can strike anyone at any age, but they are more common in older adults. Estimates of the prevalence of MPNs vary, but analysis of claims data suggests there may be as many as 200,000 people in the U.S. living with the most prevalent MPNs: myelofibrosis, polycythemia vera or essential thrombocythemia4.

About LIMBER

Incyte is a leader in the discovery and development of therapies for patients with myeloproliferative neoplasms (MPNs) and graft-versus-host disease (GVHD). The Leadership In MPNs and GVHD BEyond Ruxolitinib (LIMBER) program is designed to evaluate multiple monotherapy and combination strategies to improve and expand treatments for patients with MPNs and GVHD. The program currently has three key areas of focus: development of a new, once-daily formulation of ruxolitinib; ruxolitinib-based combinations with new targets such as PI3Kδ, BET and ALK2; and new therapeutic options such as mutant CALR.

About Incyte

Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.

Forward-Looking Statements

Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding the presentation of data from Incyte’s clinical development pipeline, whether or when any development compounds or combinations will be approved or commercially available for use in humans anywhere in the world outside of the already approved indications in specific regions and Incyte’s goal of improving the lives of patients, contain predictions, estimates and other forward-looking statements.

These forward-looking statements are based on Incyte’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; the effects of the COVID-19 pandemic and measures to address the pandemic on Incyte and its partners’ clinical trials, supply chain, other third-party providers and development and discovery operations; determinations made by the U.S. FDA and other regulatory authorities outside of the United States; the efficacy or safety of Incyte and its partners’ products; the acceptance of Incyte and its partners’ products in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; and other risks detailed from time to time in Incyte’s reports filed with the Securities and Exchange Commission, including its annual report and its quarterly report on Form 10-Q for the quarter ended September 30, 2022. Incyte disclaims any intent or obligation to update these forward-looking statements.

_______________________________
1 Reis E, et al. Discovery of INCA033989, a Monoclonal Antibody That Selectively Antagonizes Mutant Calreticulin Oncogenic Function in Myeloproliferative Neoplasms. Presented at the 64 ASH Annual Meeting, December 10-13, 2022.
2 Nagalia et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013; 369:2391-2405.
3 Klampfl T et al. Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms. N Engl J Med 2013; 369:2379-2390.
4 Data on file.

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Incyte Announces Data from Two LIMBER Studies Evaluating Combination Treatments in Patients with Myelofibrosis (MF) Presented at ASH 2022

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– Phase 2 data demonstrate that the addition of parsaclisib to ruxolitinib (Jakafi®) resulted in spleen volume reduction and improvement in symptom burden in patients with myelofibrosis (MF)

– Initial results of a Phase 1/2 study evaluating the safety and tolerability of INCB00928, an ALK2 inhibitor, show INCB00928 improves anemia in patients with MF both as monotherapy and in combination with ruxolitinib

– These studies are part of our LIMBER program evaluating ruxolitinib combinations and potential new targets for appropriate patients with myeloproliferative neoplasms (MPNs)

WILMINGTON, Del.–(BUSINESS WIRE)–Incyte (Nasdaq:INCY) today announced new data from two of its LIMBER (Leadership In MPNs and GVHD BEyond Ruxolitinib) trials evaluating monotherapy and combination strategies using ruxolitinib (Jakafi®) with parsaclisib, its investigational phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, and INCB00928 (zilurgisertib), its activin receptor-like kinase (ALK2) inhibitor, in patients with myelofibrosis (MF). These Phase 2 and Phase 1/2 trials (Abstract #236 and Abstract #1714, respectively) were presented at the 64th American Society of Hematology (ASH) Annual Meeting, held December 10-13, 2022, in New Orleans and virtually1,2.

“MF is a rare, chronic blood cancer, and despite the advancements made in treatment, additional options are needed”

“Despite the significant advances we have made in the treatment of myeloproliferative neoplasms (MPNs) like MF, a need for additional options remains for those who have an inadequate response to or are unable to tolerate current therapies,” said Peter Langmuir, M.D., Vice President, Oncology Drug Development, Incyte. “The parsaclisib and ruxolitinib data presented at ASH demonstrate the clinical potential of the combination to improve upon the standard of care and continue to support the safety profile. We look forward to building on these results through our Phase 3 LIMBER-304 and LIMBER-313 trials evaluating parsaclisib as an add-on to ruxolitinib and in the frontline setting, both of which are currently underway.”

Final results from the Phase 2 trial (Abstract #236; NCT02718300) evaluating the efficacy and safety of add-on parsaclisib to ruxolitinib for patients with MF who had a suboptimal response to ruxolitinib resulted in additional spleen volume reduction and improvement in symptom burden with add-on parsaclisib. Patients in the trial received parsaclisib daily for eight weeks in combination with stable dose ruxolitinib and then daily or weekly thereafter. Patients who received an all daily parsaclisib dosing schedule appeared to have a more durable efficacy profile compared with daily followed by weekly dosing of parsaclisib. Specifically:

  • At 12 weeks of treatment, 59.5% (25), 21.4% (9) and 4.8% (2) of patients who received all daily dosing experienced ≥10%, ≥25% and ≥35% reduction in spleen volume, respectively.
    • Comparatively, 28.1% (9), 3.1% (1) and 0% of patients who received daily followed by weekly dosing experienced ≥10%, ≥25% and ≥35% reduction in spleen volume, respectively.
  • At 24 weeks of treatment the reduction was maintained, with 50% (21), 28.6% (12) and 7.1% (3) patients who received all daily dosing experiencing ≥10%, ≥25% and ≥35% reduction in spleen volume, respectively.
    • Comparatively, 12.5% (4), 12.5% (4) and 3.1% (1) of patients who received daily followed by weekly dosing experienced ≥10%, ≥25% and ≥35% reduction in spleen volume, respectively.
  • Addition of parsaclisib to ruxolitinib was generally well-tolerated, with limited grade 3 or 4 adverse events and treatment-emergent adverse event (TEAE)-related discontinuations. TEAEs common to PI3Kδ inhibitors in lymphoma (e.g., hepatotoxicity, rash, colitis) were infrequent or absent with the addition of parsaclisib.
    • Serious TEAEs occurring in ≥2 patients overall included pneumonia (n=6; 2 daily/weekly, 1 all daily), fall (n=3; 2 daily/weekly, 1 all daily) and pyrexia (n=2; 1 daily/weekly, 1 all daily).
    • Overall, 9 patients (5 daily/weekly, 4 all daily) had a TEAE leading to parsaclisib discontinuation, and 4 patients (2 daily/weekly, 2 all daily) had a TEAE leading to ruxolitinib discontinuation.

“MF is a rare, chronic blood cancer, and despite the advancements made in treatment, additional options are needed,” said Abdulraheem Yacoub, Associate Professor, Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center. “I am encouraged by these findings and the potential of parsaclisib and ruxolitinib to be an efficacious combination therapy to help improve outcomes for certain patients living with MF.”

Additionally, data from a Phase 1/2 open-label, dose escalation and expansion study (Abstract #1714; NCT04455841) assessing the safety and tolerability of INCB00928 (zilurgisertib), a potent and selective ALK2 inhibitor, as monotherapy or in combination with ruxolitinib in patients with anemia due to MF were presented at ASH. Anemia occurs in more than one-third of patients at MF diagnosis and can be exacerbated during treatment3,4. Initial results of the study observed reduction in post-dose hepcidin levels at all dose levels and observed improvements in anemia among patients treated in both the monotherapy and combination cohorts, which suggest the potential for therapeutic activity. The data also support once-daily dosing of INCB00928 and continued dose escalation to achieve optimal exposure. Treatment with INCB00928 monotherapy and in combination with ruxolitinib resulted in predominantly grade 1/2 TEAEs and no dose-limiting toxicities (DLTs). Few grade ≥3 TEAEs were observed, including thrombocytopenia in two patients with baseline grade 2 thrombocytopenia, and neutropenia in one patient with baseline grade 2 neutropenia. No TEAEs led to study drug discontinuation.

More information regarding the congress and the more than 50 abstracts from Incyte’s oncology portfolio being featured at the meeting is available on the ASH website: https://www.hematology.org/meetings/annual-meeting.

About Myeloproliferative Neoplasms

Myeloproliferative neoplasms (MPNs) are a closely related group of blood cancers in which the bone marrow functions abnormally. The bone marrow is where the body’s blood cells are made. MPNs are progressive blood cancers that can strike anyone at any age, but they are more common in older adults. Estimates of the prevalence of MPNs vary, but analysis of claims data suggests there may be as many as 200,000 people in the U.S. living with the most prevalent MPNs: myelofibrosis, polycythemia vera or essential thrombocythemia5.

About LIMBER

Incyte is a leader in the discovery and development of therapies for patients with myeloproliferative neoplasms (MPNs) and graft-versus-host disease (GVHD). The Leadership In MPNs and GVHD BEyond Ruxolitinib (LIMBER) program is designed to evaluate multiple monotherapy and combination strategies to improve and expand treatments for patients with MPNs and GVHD. The program currently has three key areas of focus: development of a new, once-daily formulation of ruxolitinib; ruxolitinib-based combinations with new targets such as PI3Kδ, BET and ALK2; and new therapeutic options such as mutant CALR.

About Jakafi® (ruxolitinib)

Jakafi® (ruxolitinib) is a JAK1/JAK2 inhibitor approved by the U.S. FDA for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea; intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults; steroid-refractory acute GVHD in adult and pediatric patients 12 years and older; and chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older6.

Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi® (ruxolitinib) outside the United States. Jakafi is a registered trademark of Incyte Corporation. Jakavi is a registered trademark of Novartis AG in countries outside the United States.

Important Safety Information

Jakafi can cause serious side effects, including:

Low blood counts: Jakafi® (ruxolitinib) may cause low platelet, red blood cell, and white blood cell counts. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will do a blood test to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.

Cancer: Some people have had certain types of non-melanoma skin cancers during treatment with Jakafi. Your healthcare provider will regularly check your skin during your treatment with Jakafi. Tell your healthcare provider if you develop any new or changing skin lesions during treatment with Jakafi.

Increases in cholesterol: You may have changes in your blood cholesterol levels during treatment with Jakafi. Your healthcare provider will do blood tests to check your cholesterol levels about every 8 to 12 weeks after you start taking Jakafi, and as needed.

Increased risk of major cardiovascular events such as heart attack, stroke or death in people who have cardiovascular risk factors and who are current or past smokers while using another JAK inhibitor to treat rheumatoid arthritis: Get emergency help right away if you have any symptoms of a heart attack or stroke while taking Jakafi, including: discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back, severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw, pain or discomfort in your arms, back, neck, jaw, or stomach, shortness of breath with or without chest discomfort, breaking out in a cold sweat, nausea or vomiting, feeling lightheaded, weakness in one part or on one side of your body, slurred speech

Increased risk of blood clots: Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) have happened in people taking another JAK inhibitor for rheumatoid arthritis and may be life-threatening. Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with Jakafi, including: swelling, pain, or tenderness in one or both legs, sudden, unexplained chest or upper back pain, shortness of breath or difficulty breathing

Possible increased risk of new (secondary) cancers: People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers. People who smoke or who smoked in the past have an added risk of new cancers.

The most common side effects of Jakafi include: for certain types of myelofibrosis (MF) and polycythemia vera (PV) – low platelet or red blood cell counts, bruising, dizziness, headache, and diarrhea; for acute GVHD – low platelet counts, low red or white blood cell counts, infections, and swelling; and for chronic GVHD – low red blood cell or platelet counts and infections including viral infections.

These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Call your doctor for medical advice about side effects.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had low white or red blood cell counts, have or had tuberculosis (TB) or have been in close contact with someone who has TB, had shingles (herpes zoster), have or had hepatitis B, have or had liver or kidney problems, are on dialysis, have high cholesterol or triglycerides, had cancer, are a current or past smoker, had a blood clot, heart attack, other heart problems or stroke, or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change your dose or stop taking Jakafi without first talking to your healthcare provider.

Women should not take Jakafi while pregnant or planning to become pregnant. Do not breastfeed during treatment with Jakafi and for 2 weeks after the final dose.

Please see the Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi.

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.

About Incyte

Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.

Forward-Looking Statements

Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding the presentation of data from Incyte’s clinical development pipeline, whether or when any development compounds or combinations will be approved or commercially available for use in humans anywhere in the world outside of the already approved indications in specific regions and Incyte’s goal of improving the lives of patients, contain predictions, estimates and other forward-looking statements. These forward-looking statements are based on Incyte’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; the effects of the COVID-19 pandemic and measures to address the pandemic on Incyte and its partners’ clinical trials, supply chain, other third-party providers and development and discovery operations; determinations made by the U.S. FDA and other regulatory authorities outside of the United States; the efficacy or safety of Incyte and its partners’ products; the acceptance of Incyte and its partners’ products in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; and other risks detailed from time to time in Incyte’s reports filed with the Securities and Exchange Commission, including its annual report and its quarterly report on Form 10-Q for the quarter ended September 30, 2022. Incyte disclaims any intent or obligation to update these forward-looking statements.

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1 Yacoub A, et al. Efficacy and Safety of Add-on Parsaclisib to Ruxolitinib Therapy in Myelofibrosis Patients With Suboptimal Response to Ruxolitinib: Final Results From a Phase 2 Study. Presented at the 64th ASH Annual Meeting, December 10-13, 2022.
2 Mohan S, et al. A Phase ½ Study of INCB000928 As Monotherapy or Combined with Ruxolitinib (RUX) in Patients (Pts) with Anemia Due to Myelofibrosis (MF). Presented at the 64th ASH Annual Meeting, December 10-13, 2022.
3 Tefferi A, et al. Mayo Clin Proc. 2012;87(1):25-33.
4 Naymagon L, Mascarenhas J. Hemasphere. 2017;1(1):doi: 10.1097/HS1099.0000000000000001.
5 MPN Research Foundation. “MPN Landmark Survey.” Available at: https://www.mpnlandmarksurvey.com/pdf/mpn-landmark-survey-summary.pdf. Accessed February 2019.
6 Jakafi (ruxolitinib) tablets: Prescribing Information. U.S. Food and Drug Administration.

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Verstovsek Highlights Future Directions for MPN Treatments

Posted on by
Jordyn Sava

In an interview with Targeted Oncology, Srdan Verstovsek, MD, discussed the current MPN treatment landscape and where the field is shifting.

For patients with myeloproliferative neoplasms (MPNs), JAK inhibition has become an important therapeutic approach for treatment. Particularly for patients with myelofibrosis (MF), JAK inhibitors have allowed for reduction in symptoms and better outcomes.

The first JAK inhibitor to make its debut in the MPN treatment landscape was ruxolitinib (Jakafi), followed by the FDA approval of fedratinib (Inrebic) in 2019. Since then, experts have continued to make advancements with novel therapeutic strategies.

With now over 10 ongoing phase 3 trials around the world, investigators are combining novel treatments with JAK inhibitors to develop new options to use when treating patients with MPNs, including polycythemia vera (PV), essential thrombocytopenia (ET), and myelofibrosis.

“We are looking first to see whether the combinations that are exploring enhancement of the control of the sign symptoms on top of JAK inhibitors will do that well, well enough to be approved and then considered in everyday practice. We are also looking in the near future to see whether any of these therapies can prolong life,” said Srdan Verstovsek, MD, in an interview with Targeted OncologyTM.

In the interview, Verstovsek, associate professor of medicine in the Leukemia department at the University of Texas MD Anderson Cancer Center, discussed the current MPN treatment landscape and where the field is shifting.

Targeted Oncology: Can you describe the current treatment landscape for essential thrombocytopenia?

Verstovsek: In essential thrombocythemia or ET, we worry about the thrombotic risk and our priority is to decrease it. We define the patients that are at an increased risk of blood clotting by applying certain prognostic factors. A significant change in the prognostication happened several years ago, which is now incorporated in United States based guidance, the NCCN guidelines. This is to say that in addition to historical factors of age over 60, or history of blood clotting, now, we also account for a presence or absence of a JAK2 mutation, which is present in about 60% of ET patients and it drives the disease process.

Therefore, there is a significant shift in identifying those that are at high risk of blood clotting by adding a JAK2 mutation presence to age. So, patients that are older than 60 and have a JAK2 mutation are the high-risk patients or of course, those that have a history of blood clotting. There is also an attempt to improve our management of these patients. Standard practice is to prescribe hydroxyurea, which is chemotherapy by mouth, to decrease the blood cell count. Then anagrelide is a second-line agent which inhibits the growth of the cells in the bone marrow that make platelets, so it lowers the platelets.

There is a phase 3 randomized study underway comparing anagrelide to a new agent that has the potential to be active in ET as it is in PV for which is already approved. I’m talking about ropeginterferon alfa-2b-njft [Besremi]. That study is a global randomized study comparing ropeginterferon to rusfertide, to prove the point that ropeginterferon might be better in controlling the platelets and the white cells that may be elevated sometimes in his patients. Hopefully, we are not going to have only to implement a prognostication and identification of the patients that need to be treated, otherwise, you just give them aspirin, but also more therapies to offer. Right now, it’s hydrea. And for interferon if we can get it off label, this will be onlabel as a second-line choice in the near future if the study is successful.

What has recently been seen in the polycythemia vera and myelofibrosis spaces?

Where in essential thrombocythemia we worry about thrombotic risk, we phlebotomize the patients to decrease the hematocrit, which is a measure of the percent of blood made from red blood cells in polycythemia vera and we give patients aspirin to make a blood flow easier. In some patients older than 60 or those that have a history of blood clots, we give them cytoreductive therapy to decrease the red blood cells, white cells, and platelets. Again, we use hydroxyurea for ET. But now ropeginterferon was approved last November for PV. It is a long acting interferon and the guidance now says that one could consider 1 or the other meaning, hydrea or ropeginterferon as a frontline choice. Then in a second-line, we have standard practice drug ruxolitinib, a JAK inhibitor, which is actually approved for hydroxyurea-resistant, -refractory, or -intolerant patients.

In this setting, there is another drug that is being developed in a phase 3 randomized study for possible approval. It’s called rusfertide. It’s a hepcidin mimetic and hepcidin is an important protein in the blood that modulates the iron metabolism. That medication would mimic what it does and keep the iron inside the liver, for example, or spleen, or a lining of the [gastrointestinal] tract. That’s called a radical endothelial system in the body. That would decrease the iron availability for the red blood cells and that would lead to elimination of the need for phlebotomy, which is very important, and people may feel better. At the moment, there is a phase 3 randomized placebo-controlled study in patients that need too many phlebotomies with a goal to approve rusfertide in the near future as another agent for these patients with PV.

Then, myelofibrosis is the most aggressive of MPNs with a shorter life expectancy. Here we have a plethora of different studies underway. The most important part is that in addition to ruxolitinib and fedratinib, this year, we have also pacritinib approved which is another JAK inhibitor and it can be given to patients with low platelets. Then, there is the recent application for possible approval of another JAK inhibitor called momelotinib, which is quite different from the others. It can improve anemia and eliminate the need for transfusions. The phase 3 randomized study of momelotinib vs danazol has completed and the results are good, and an application for approval is in place. By next summer, we may have momelotinib the fourth drug approved from myelofibrosis which will be perfect for patients who have suffered from anemia.

Can you further explain ruxolitinib and its mechanism of action?

Ruxolitinib inhibits JAK1 and JAK2, 2 of 4 members of JAK enzymes that are important in the body for function relative to blood making inflammation in the immune system. In particular, the JAK2 enzyme is associated with the growth factors and mechanisms of cell growth for red blood cells and platelets. JAK1 and JAK2 are also involved heavily in inflammation.Ruxolitinib will inhibit the proliferation and inflammation. People with myelofibrosis, for example, have a smaller spleen because of therapy, and that is why people feel much better, because it’s anti-inflammatory. On the other hand, it can lower the platelets through myelosuppression and that’s why we need to balance when we can give it. We like to give it as early as possible in the life of the patients and when the patients are not too sick. It’s easier to give it, it is a good dose, and the results are much better with earlier intervention.

In polycythemia vera, ruxolitinib is valuable as a second-line choice when things don’t go well with hydroxyurea. Patients then have much higher white blood cell counts, may have a big spleen, and of course, require phlebotomy. In that setting, it has been proven in 2 randomized studies that ruxolitinib provides a significant clinical benefit in normalizing blood cell count, improving quality of life, and decreasing spleen in those that have a big spleen. It appears after many years of follow-up that this is very durable, and possibly decreases the risk of early death from the complications of uncontrolled polycythemia vera. We use it often in the second-line setting, and it is a number 1 choice in PV.

What unmet needs still exist regarding MPNs?

In any of these three conditions, ET, PV, or myelofibrosis, we are talking about decreasing thrombotic risk, controlling the blood cell count, improving the quality of life, and decreasing the spleen. We don’t really have drugs that would eliminate disease or make it controllable forever. More active drugs that will be much more durable and perhaps that can be achieved by combinations [are needed]. For example, in myelofibrosis, we’re witnessing a flurry of phase 3 randomized studies where novel agents are combined with the JAK inhibitor ruxolitinib to make it even better and perhaps longer lasting in controlling signs and symptoms. I would like to see agents like interferon that have a potential that can lower, and perhaps eliminate malignant clones.

What are the future directions in this space?

We are looking first to see whether the combinations that are exploring enhancement of the control of the sign symptoms, on top of JAK inhibitors, will actually do that well or well enough to be approved and considered everyday practice. We are also looking in the very near future to see whether any of these therapies can prolong life. Overall survival is already in 1 study with a possible approval with the drug called imetelstat, which is a telomerase inhibitor, a primary goal. This is a phase 3 randomized study in a second-line setting.

Then to enhance that, perhaps not in a year but in 3-5 years, that effect of the potential targeted agents to bring about the molecular response, and that would mean possibly a complete response and partial response. We are at the beginning of the new phase in developing the drugs, not just to talk about improvement in the number or the size of the spleen or a blood cell count, but also to talk about affecting the malignant clone.

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