Update on Therapeutic Options for Myelofibrosis

Posted on March 21, 2023March 21, 2023 by mpn_admin

March 19, 2023

Sara M. Tinsley-Vance, PhD, APRN, AOCN

Myelofibrosis is a rare hematologic malignancy associated with abnormal blood counts, splenomegaly, symptoms of chronic inflammation, and scarring of the bone marrow. Prognosis varies, although in most cases is poor. Without hematopoietic stem cell transplant, cure is not possible.

Characteristics of the disease, goals of treatment, and new treatment strategies were discussed in an oral presentation at the 2023 ONA Summit Live Virtual Meeting.

Treatment is focused on alleviation of symptoms, management of cytopenias, and prevention of complications. Current care is focused on inhibition of altered signaling of the JAK/STAT pathway. Ruxolitinib, fedratinib, and pacritinib are FDA-approved for intermediate- and high-risk myelofibrosis. Ruxolitinib was the first in class, JAK 1 and 2 inhibitor, approved in 2011 based on spleen volume reduction and improvement in myelofibrosis-related symptoms.

Fedratinib was approved in 2019 and pacritinib in 2022. Both fedratinib and pacritinib have the potential for spleen volume reduction, and symptom improvement. Pacritinib provides a treatment option for patients with thrombocytopenia.

A new drug application for momelotinib, a JAK1/JAK2/ACVR1/ALK2 inhibitor, was recently accepted by the US FDA. In the MOMENTUM clinical trial (ClinicalTrials.gov Identifier: NCT04173494), momelotinib met all primary and secondary endpoints. Spleen volume response, improvement in symptoms, and transfusion independence were achieved with this new agent.

Nurses and other allied healthcare professionals can benefit from understanding myelofibrosis, potential treatments, adverse side effects, and recommendations for monitoring to educate patients and engage them in discussion for shared decision-making.

Sara Tinsley-Vance is a nurse practitioner and quality of life researcher in the Malignant Hematology Program at Moffitt Cancer Center in Tampa, Florida

Reference

Tinsley-Vance SM. Myelofibrosis: therapeutic options for a complex rare disease. Oral presentation at: 2023 ONA Summit Live Virtual Meeting; March 17-19, 2023.

Earlier Jakafi Treatment Shows Encouraging Outcomes in Myelofibrosis

Posted on March 21, 2023March 21, 2023 by mpn_admin

Published on: March 15, 2023

Brielle Benyon

Earlier treatment with Jakafi showed promise in both improving survival and symptom burden in certain patients with myelofibrosis, though physicians often delay Jakafi treatment.

A higher percentage of patients with intermediate-2 and high-risk myelofibrosis who were introduced to Jakafi (ruxolitinib) within a year of being diagnosed saw improved survival and reduced symptom burden compared to those who were given the drug later or not at all,according to recent research that was published in the journal Cancer.

Researchers analyzed data from two clinical trials (COMFORT-I and COMFORT-II), which included 525 patients with myelofibrosis, a type of myeloproliferative neoplasm.

In this patient population, 84 patients received Jakafi within 12 months of being diagnosed, while 216 received the drug at or after 12 months from diagnosis. Additionally, 66 patients received placebo plus best available therapy within 12 months, and 159 patients received placebo plus best available therapy after 12 months.

Myelofibrosis causes a decrease in the number of normal cells that are produced in the bone marrow. As a result, the spleen starts to produce these types of cells, and often becomes inflamed — indicating potentially worsening disease and putting patients at risk for infections.

“Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue,” the researchers wrote.

Study findings showed that at week 48, patients who received Jakafi earlier had a higher rate of spleen volume response (meaning that their spleen shrunk) than those who were not exposed to the drug within a year of treatment (44% versus 26.9%, respectively).

Additionally, at a 240-week follow-up, 63% of patients who were given Jakafi early were still alive, compared with 57% of those who were given the drug a year or later after being diagnosed. At this time, 49.4% of patients who received placebo plus best available therapy within 12 months were alive, and 40.7% of those given placebo/best therapy at or after 12 months were alive.

The researchers also noted that on average, patients given Jakafi — regardless of whether it was within or after 12 months of diagnosis — tended to live longer than those prescribed placebo plus best available therapy.

The Food and Drug Administration approved Jakafi for intermediate- or high-risk myelofibrosis more than a decade ago, and it is recommended to be the first therapy offered for patients with the disease. However, as the study authors pointed out, Jakafi is often not the first drug given, or it is not given soon after diagnosis.

“The National Comprehensive Cancer Network guidelines for myeloproliferative neoplasms recommend (Jakafi) as a first-line treatment for patients with higher-risk (myelofibrosis),” study authors wrote. “There is a compelling rationale to treat patients with intermediate- or high-risk (myelofibrosis) with (Jakafi). Despite this, real-world treatment patterns indicate that many physicians delay or avoid (Jakafi) treatment, often in favor of hydroxyurea or watchful waiting.”

Patient-specific comorbidities as prognostic variables for survival in myelofibrosis

Posted on March 21, 2023March 21, 2023 by mpn_admin

Andrew L. Sochacki, Cosmin Adrian Bejan, Shilin Zhao, Ameet Patel, Ashwin Kishtagari, Travis P. Spaulding, Alexander J. Silver, Shannon S. Stockton, Kelly Pugh, R. Dixon Dorand, Manasa Bhatta,

Nicholas Strayer, Siwei Zhang, Christina A. Snider, Thomas Stricker, Aziz Nazha, Alexander G. Bick, Yaomin Xu, Michael R. Savona

Abstract

Treatment decisions in primary myelofibrosis (PMF) are guided by numerous prognostic systems. Patient-specific comorbidities have influence on treatment-related survival and are considered in clinical contexts but have not been routinely incorporated into current prognostic models. We hypothesized that patient-specific comorbidities would inform prognosis and could be incorporated into a quantitative score. All patients with PMF or secondary myelofibrosis with available DNA and comprehensive electronic health record (EHR) data treated at Vanderbilt University Medical Center between 1995 and 2016 were identified within Vanderbilt’s Synthetic Derivative and BioVU Biobank. We recapitulated established PMF risk scores (eg, Dynamic International Prognostic Scoring System [DIPSS], DIPSS plus, Genetics-Based Prognostic Scoring System, Mutation-Enhanced International Prognostic Scoring System 70+) and comorbidities through EHR chart extraction and next-generation sequencing on biobanked peripheral blood DNA. The impact of comorbidities was assessed via DIPSS-adjusted overall survival using Bonferroni correction. Comorbidities associated with inferior survival include renal failure/dysfunction (hazard ratio [HR], 4.3; 95% confidence interval [95% CI], 2.1-8.9; P = .0001), intracranial hemorrhage (HR, 28.7; 95% CI, 7.0-116.8; P = 2.83e-06), invasive fungal infection (HR, 41.2; 95% CI, 7.2-235.2; P = 2.90e-05), and chronic encephalopathy (HR, 15.1; 95% CI, 3.8-59.4; P = .0001). The extended DIPSS model including all 4 significant comorbidities showed a significantly higher discriminating power (C-index 0.81; 95% CI, 0.78-0.84) than the original DIPSS model (C-index 0.73; 95% CI, 0.70-0.77). In summary, we repurposed an institutional biobank to identify and risk-classify an uncommon hematologic malignancy by established (eg, DIPSS) and other clinical and pathologic factors (eg, comorbidities) in an unbiased fashion. The inclusion of comorbidities into risk evaluation may augment prognostic capability of future genetics-based scoring systems.

Protagonist Therapeutics Announces Highly Statistically Significant Results from the Randomized Withdrawal Portion of the REVIVE Study of Rusfertide in Polycythemia Vera

Posted on March 17, 2023March 17, 2023 by mpn_admin

Rusfertide met the study’s primary endpoint, with a statistically significant higher number of responders on rusfertide versus placebo (p=0.0003)

Rusfertide continues to be generally well tolerated with no new safety signals

NEWARK, CA / ACCESSWIRE / March 15, 2023 / Protagonist Therapeutics, Inc. (NASDAQ:PTGX) (“Protagonist” or “the Company”), today announced positive topline results from the blinded, placebo-controlled, randomized withdrawal portion of REVIVE, a study evaluating rusfertide, a subcutaneous injectable hepcidin mimetic, in patients with polycythemia vera (PV). Subjects receiving rusfertide achieved highly statistically significant improvements versus placebo in the primary endpoint.

The double-blind, placebo-controlled, 12-week randomized withdrawal phase was included as Part 2 of the REVIVE study to evaluate rusfertide in PV patients with frequent phlebotomy requirements. In the trial, study subjects were initially enrolled in the 28-week open label dose-titration and efficacy evaluation Part 1 of the study, followed by 1:1 randomization of 53 subjects to placebo versus rusfertide therapy for a subsequent duration of 12 weeks (“randomized withdrawal portion” or “Part 2”).

More subjects receiving rusfertide during the blinded randomized withdrawal portion of the REVIVE study were responders compared with placebo (69.2% versus 18.5%, p=0.0003). A study subject was defined as a responder if the subject completed 12 weeks of double-blind treatment while maintaining hematocrit control without phlebotomy eligibility and without phlebotomy. During the 12 weeks of the blinded randomized withdrawal, only 2 of 26 subjects on rusfertide were phlebotomized, keeping 92.3% patients phlebotomy free in the rusfertide arm (p=0.0003).

In patients with moderate or severe Myeloproliferative Neoplasm-Symptom Assessment Form (MPN-SAF) symptom scores at baseline, the change from baseline was statistically significant in fatigue, problems with concentration, inactivity and itching during the 28-week open label Part 1 of the study. Meaningful comparison of symptom assessments in Part 2 are not possible since a majority of subjects randomized to placebo discontinued prior to the 12-week assessment of MPN-SAF symptoms.

Rusfertide was well tolerated, with localized injection site reactions comprising the majority of reported adverse events. No new safety signals were observed in these data following presentation of safety data from the REVIVE study at the American Society of Hematology (ASH) December 2022 Annual Meeting.

Additional details on these data can be found in slides 25 through 31 of the Protagonist Corporate Presentation, available on the Company’s website at protagonist-inc.com.

“Participants in our studies who required frequent phlebotomy, with or without cytoreductives, have now been treated with rusfertide for more than two years, remaining largely phlebotomy free,” said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. “Data from the REVIVE study suggest that rusfertide treatment results in a highly statistically significant reduction in the need for therapeutic phlebotomy in phlebotomy-dependent patients, leading to rapid, sustained, and durable control of hematocrit levels below 45%. Part 2 of REVIVE, the randomized withdrawal study, yielded no new safety findings while confirming previously reported efficacy and safety findings observed in the open label portion of REVIVE (Part 1).”

“These randomized withdrawal data from the REVIVE study indicate a dramatic difference in the experience of the treatment group versus the placebo group,” noted Dr. Ronald Hoffman, M.D., the Albert A. and Vera G. List Professor of Medicine (Hematology and Oncology), Director of the Myeloproliferative Research Program at the Icahn School of Medicine at Mount Sinai, and principal investigator of the study. “With robust and strongly positive results observed across a diverse set of patients, we now have further confirmation of rusfertide’s potential to serve as an important future treatment option for patients with polycythemia vera.”

“All study subjects who participated in the REVIVE clinical trial had been previously unsuccessful in controlling their hematocrit using standard-of-care therapies alone,” said Andrew Kuykendall, M.D., Department of Malignant Hematology, Moffit Cancer Center. “These new data from REVIVE provide important insights into the role that rusfertide (PTG-300) can potentially have within a future PV treatment paradigm, supporting patients and their physicians in achieving the treatment goal of hematocrit below 45%, in step with current NCCN Clinical Practice Guidelines.”

“The new randomized withdrawal data confirm our previous efficacy and safety findings of rusfertide in PV and support our strong conviction that rusfertide can be a potentially transformational therapeutic option for polycythemia vera,” said Dinesh V. Patel, Ph.D., President and Chief Executive Officer of Protagonist. “With the completion of the REVIVE study, the Company’s topmost priority continues to be execution of the 250-patient global, pivotal, Phase 3 VERIFY study in PV. The Protagonist team continues to work with full dedication alongside investigators, site staff and other partners with the shared aim of bringing this important potential therapy to PV patients.”

Novel Treatments Give Hope for a Transformed Transplant Community

Posted on March 17, 2023March 17, 2023 by mpn_admin

March 15, 2023

Improvements in graft-vs-host disease and transplant-related mortality have created a wave of hope for clinicians treating their patients with hematologic malignancies, stemming from the encouraging data seen with Orca-T and other novel therapeutics in the pipeline.

Improvements in graft-vs-host disease (GVHD) and transplant-related mortality have created a wave of hope for clinicians treating their patients with hematologic malignancies, stemming from the encouraging data seen with Orca-T and other novel therapeutics in the pipeline.

For example, at the 2023 Transplantation and Cellular Therapy Meetings, data from a single-center phase 2 trial showed that Orca-T, which is a high precision cell therapy, produced a 100% overall survival rate in 8 patients with acute leukemia, myeloproliferative neoplasms, chronic myeloid leukemia, and other hematologic cancers who underwent an allogeneic hematopoietic stem cell transplant with 7/8 non-permissive haploidentical mismatched donors.¹

The immune reconstitution of Orca-T in 100 patients from an ongoing, multicenter phase 1b trial (NCT04013685) was also examined in findings presented at the 2022 ASH Annual Meeting. Investigators performed longitudinal measurements of immune reconstitution, showcasing the peripheral blood counts of platelets, white blood cells, neutrophils, lymphocytes, monocytes, T cells, B cells, and natural killer (NK) cells. Results showed that patients on Orca-T exhibited early immune reconstitution in each of the key leukocyte and lymphocyte subsets believed to manage relapse and infection.²Researchers also observed elevated Treg frequencies. Overall, these immune reconstitution data may be correlated to the reduced occurrence and severity of acute and chronic GVHD.

In an interview with OncLive^®, Lori Muffly, MD, an associate professor of medicine at Stanford University, discussed the updated findings with Orca-T in hematologic malignancies, spoke to the product’s immune reconstitution profile, and the next steps she hopes to see taken with this type of treatment and others in the pipeline.

OncLive: Orca-T has been an agent to watch for over the last few years. Updated findings were presented at the 2022 ASH Annual Meeting, as well as some at the 2023 Transplantation and Cellular Therapy Meetings. Could you highlight the topline data reported at both meetings?

Muffly: We are really excited about Orca-T in the transplant community. The data have been presented a few times now from the single-center phase 2 and multicenter phase 1b studies . In the matched setting, which has been presented multiple times, what has been shown is low rates of both acute and chronic GVHD, and incredibly low rates of transplant-related mortality.

For someone like me, who treats patients with typically adverse risk of acute leukemia, I think the most exciting part is seeing that the relapse rates appear to be not increased in any way compared with our historical tacrolimus/methotrexate GVHD prophylaxis. That is very exciting because having overall survival rates that are phenomenal, low relapse rates, and then particularly low GVHD and transplant-related mortality rates, is exactly what we’re looking for in the field of transplant.

There were some immune reconstitution data with Orca-T that were presented at the 2022 ASH Annual Meeting. What were the key takeaways from that?

One of the other nice things about the Orca-T platform, which is really a reduced T-cell dose, along with an administration of regulatory T cells, is that the infection rates are quite low, relative to historical control. One of the problems with more of a traditional T-cell depleted graft, either ex vivo or in vivo, is higher rates of infection, particularly viral infections. We have not seen that with Orca-T.

At this past year’s ASH Annual Meeting, there was a poster demonstrating in about 90 patients, at least with day 28 data, and then around 50 patients with 1 year of follow-up, the immune cell subset reconstitution. What we could see is that these patients reconstituted B cells, T cells, regulatory T cells and NK cells by 1 year, quite effectively. That probably has something to do with why we’re seeing lower rates of infection than as predicted in a T-cell deplete graft.

Putting it into context for the practicing clinician, why is immune reconstitution important and how do we use it to guide treatment decisions for patients?

With transplant, there are so many different factors that we think about—of course, a focus on the disease itself that we’re transplanting for. For example, if a patient has acute myeloid leukemia, trying to get a transplant that has the most potential for graft vs leukemia is important. We think about GVHD, because that is the adverse flip side of graft vs leukemia and identifying mechanisms of transplant that are associated with lower GVHD is important.

Then finally, the ability of the new graft to protect patients from infection and particularly opportunistic infection and viral reactivations [are what we think about]. Any 1 of those 3 components that’s missing is a big problem for our patients. If you have a transplant approach that really can take care of all 3 [components], that is really the holy grail of transplant: low relapse, low GVHD, and low infection.

Taking these data into context, what next steps would you like to see taken with this type of therapy?

I am really excited about the possibilities with Orca-T. Currently, as you probably know, there is a randomized phase 3 study, a registration trial, ongoing comparing Orca-T with historical control tacrolimus and methotrexate [and alloHSCT]. We have been very actively participating in that study. Obviously, we are hopeful to see the results and that this may lead to commercialization of this product.

We’re also really excited about Orca-T in the mismatched myeloablative setting. There was an oral abstract at the [2023 Transplantation and Cellular Therapy Meetings] presented with just under 10 patients with mismatched, unrelated donors. Those data look exciting, as well. There is a lot of opportunity for this program in the clinical space.

Now, the other thing that’s happening in the transplant community, which is very difficult to miss, is the evolution and uptake of posttransplant cyclophosphamide as GVHD prevention. We are really blessed right now that we have 2 exciting approaches going on at the same time: posttransplant cyclophosphamide and Orca-T. The field eventually will want to look at the 2 of them side by side, because they both seem to lead to low GVHD rates without an increase in disease relapse. As someone who offers these treatments to my patients, I have never been more excited about what we have going on in this field. I look forward to future studies as well.

Is there anything else that you think would be important for the practicing oncologist to know about these or any other therapies in the pipeline?

It is important for the practicing oncologist to know that as our therapeutics for blood cancers are improving, so are our approaches to bone marrow transplant. I no longer think about transplant-related mortalities of 20% to 30% when I’m talking to patients, and that’s how things started, at least when I started. I’m now hopeful that that sort of topline number is going to be more like a 5% risk [as more options become available]. While that’s still too high, it’s at least a bit more acceptable.

Also, the likelihood of developing GVHD with these newer approaches has substantially gone down. That is important for referring physicians to know because the darker days, scarier days, of transplant are behind us. This is a therapeutic that has curative potential for many, many adults out there. Many patients just are not referred. These data are important to get out there so that people in the community can realize transplant data are looking different than they used to look.

References

Pavlova A, Lowsky R, Muffly L, et al. Orca-T, a high-precision cell therapy, for the treatment of hematologic malignancies in patients with 7/8 mismatch donors. Presented at: 2023 Transplantation & Cellular Therapy Meetings of ASCT and CIBMTR; February 15-19, 2023; Orlando, FL. Abstract 30.
Meyer EH, Killian MS, Pavlova A, et al. Rapid immune reconstitution and elevated regulatory T cell frequencies in patients treated with Orca-T. Blood. 2022;140(suppl 1):7656-7657. doi:10.1182/blood-2022-164468

Earlier Jakafi Treatment Shows Encouraging Outcomes in Myelofibrosis

Posted on March 17, 2023March 17, 2023 by mpn_admin

Published on: March 15, 2023

Earlier treatment with Jakafi showed promise in both improving survival and symptom burden in certain patients with myelofibrosis, though physicians often delay Jakafi treatment.

Researchers analyzed data from two clinical trials (COMFORT-I and COMFORT-II), which included 525 patients with myelofibrosis, a type of myeloproliferative neoplasm.

Incyte Announces Data from Across its Oncology Portfolio will be Presented at the AACR Annual Meeting 2023

Posted on March 15, 2023March 15, 2023 by mpn_admin

Tue, March 14, 2023 at 6:30 PM EDT

WILMINGTON, Del., March 14, 2023–(BUSINESS WIRE)–Incyte (Nasdaq:INCY) today announced that multiple abstracts from across its oncology portfolio will be presented during the upcoming American Association for Cancer Research (AACR) Annual Meeting 2023, held April 14-19, in Orlando, Florida.

“As Incyte continues to advance research in areas where we believe we can have the biggest impact for patients, we look forward to sharing new pre-clinical and clinical data from our expansive oncology portfolio at this year’s AACR,” said Steven Stein, M.D., Chief Medical Officer, Incyte. “Notably, a plenary session will feature data on pemigatinib in previously-treated solid tumors with activating FGFR1–3 alterations, and five-year results from the L-MIND study of tafasitamab (Monjuvi^®) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will be highlighted in a late-breaking oral presentation.”

Key abstracts from Incyte-sponsored and partner programs include:

Oral Presentation in a Plenary Session

Pemigatinib

Clinical and Translational Findings of Pemigatinib in Previously Treated Solid Tumors with Activating FGFR1–3 Alterations in the FIGHT-207 Study (Abstract #CT016. Session: Novel Biomarker-Driven Molecularly Targeted Therapy Trials. Tuesday, April 18, 2023, 10:15 a.m. – 10:30 a.m. ET)

Oral Presentation

INCB123667 (CDK2)

Development of a CDK2-Selective Small Molecule Inhibitor INCB123667 for the Treatment of CCNE1hi Breast Cancers (Abstract #1143. Session: Small Molecule Therapeutic Agents. Sunday, April 16, 2023, 3:52 p.m. – 4:07 p.m. ET)

Tafasitamab

Five-Year Safety and Efficacy of Tafasitamab in Patients with Relapsed or Refractory DLBCL: Final Results from the Phase 2 L-MIND Study¹ (Abstract #CT022. Session: Novel Clinical Trials for Hematological Malignancies. Sunday, April 16, 2023, 3:20 p.m. – 3:30 p.m. ET)

Poster Presentations

INCA33890 (PD-1×TGFbR2)

INCA33890, a Novel PD-1×TGFbR2 Bispecific Antibody Conditionally Antagonizes TGF Signaling in Primary Immune Cells Co-expressing PD-1 (Abstract #2936. Session: Therapeutic Antibodies 2. Monday, April 17, 2023, 1:30 p.m. – 5:00 p.m. ET)

INCB098377 (PI3Kδ)

Discovery of INCB098377: a Potent Inhibitor of Phosphoinositide 3-Kinase-Gamma (Abstract #5162. Session: Modifiers of the Tumor Microenvironment. Tuesday, April 18, 2023, 1:30 p.m. – 5:00 p.m. ET)

LIMBER (MPN)

A Phase 1 Study of Ruxolitinib in Combination with Abemaciclib for Patients with Primary or Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (Abstract #CT242. Session: Phase 1 and First-in-Human Clinical Trials in Progress. Tuesday, April 18, 2023, 1:30 p.m. – 5:00 p.m. ET)

Preclinical Characterization of the BET Inhibitor, INCB057643, in Combination with Ruxolitinib for Treatment of Myeloproliferative Neoplasms (MPN) (Abstract #6274. Session: Epigenetics. Wednesday, April 19, 2023, 9:00 a.m. – 12:30 p.m. ET)

Pemigatinib

Drug Combination Screen Identifies Pemigatinib, an FGFR Inhibitor, as a Mechanism to Overcome KRASG12C Inhibitor Resistance in Lung Cancer (Abstract #412. Session: Drug Resistance in Molecular Targeted Therapies 2. Sunday, April 16, 2023, 1:30 p.m. – 5:00 p.m. ET)

Pemigatinib, an FGFR Inhibitor, Overcomes Resistance to KRASG12C Inhibitors in Mesenchymal-Like NSCLC Tumors (Abstract #430. Session: Drug Resistance in Molecular Targeted Therapies 2. Sunday, April 16, 2023, 1:30 p.m. – 5:00 p.m. ET)

P-Selectin Glycoprotein Ligand-1

P-Selectin Glycoprotein Ligand-1 Modulates the Functions of Human T Cells and Macrophages in Vitro (Abstract #6373. Session: Immune Checkpoints. Wednesday, April 19, 2023, 9:00 a.m. – 12:30 p.m. ET)

Tafasitamab

Combination of BTK Inhibitor Orelabrutinib, Anti-CD19 Antibody Tafasitamab, and IMiD Lenalidomide for the Treatment of B Cell Malignancies² (Abstract #4013. Session: Tyrosine Kinase and Phosphatase Inhibitors 1. Tuesday, April 18, 2023, 9:00 a.m. – 12:30 p.m. ET)

Preclinical Study of CD19 Detection Methods Using Monoclonal Antibodies Post Tafasitamab Treatment1 (Abstract #6329. Session: Anticancer Immunotherapeutics. Wednesday, April 19, 2023, 9:00 a.m. – 12:30 p.m. ET)

Zilurgisertib

Clinical Trial Simulation to Inform Dose Selection of Zilurgisertib, an ALK2 inhibitor, in Patients with Anemia Due to Myelofibrosis (MF) (Abstract #CT243. Session: Phase 1 and First-in-Human Clinical Trials in Progress. Tuesday, April 18, 2023, 1:30 p.m. – 5:00 p.m. ET)

For registered attendees, the virtual meeting platform and all on-demand sessions will be available through July 19, 2023. More information regarding the AACR Annual Meeting 2023 can be found at https://www.aacr.org/meeting/aacr-annual-meeting-2023/.

About Pemazyre^® (pemigatinib)
Pemazyre is a kinase inhibitor indicated in the United States for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test³. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Pemazyre is also 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.

In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion gene, worsening after cancer chemotherapy.

In Europe, Pemazyre is approved for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.

Pemazyre is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations.

Pemazyre is marketed by Incyte in the United States, Europe and Japan.

Pemazyre is a trademark of Incyte Corporation.

About Tafasitamab (Monjuvi^® / Minjuvi^®)
Tafasitamab is a humanized Fc-modified CD19 targeting immunotherapy. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb^® engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

In the United States, Monjuvi^® (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, Minjuvi^® (tafasitamab) received conditional marketing authorization in combination with lenalidomide, followed by Minjuvi^® monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Monjuvi^® and Minjuvi^® are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name MONJUVI^® in the U.S., and marketed by Incyte under the brand name Minjuvi^® in Europe and Canada.

XmAb^® is a registered trademark of Xencor, Inc.

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 older³.

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.

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 for the year ending December 31, 2022. Incyte disclaims any intent or obligation to update these forward-looking statements.

Dr. Rampal on the Role of JAK Inhibitors in Myelofibrosis

Posted on March 15, 2023March 15, 2023 by mpn_admin

Mar 14, 2023

Raajit K. Rampal, MD, PhD

Raajit K. Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center, discusses how the role of JAK inhibitors will continue to evolve in the treatment of patients with myelofibrosis.

patients with myelofibrosis, Rampal begins. However, it is not believed that JAK inhibitors modify the disease, and their effects can be limited in subgroups of patients, Rampal says.

Multiple JAK inhibitors are now available for the treatment of myelofibrosis, and this has allowed select patients to potentially be cycled between different agents, Rampal explains. As more data have emerged, they have been able to demonstrate how various JAK inhibitors can effect patients differently, and this may put clinicians in a position to better select certain JAK inhibitors for select patients, Rampal emphasizes.

Within the next 2 to 3 years, it is possible that the treatment landscape for patients with myelofibrosis will drastically shift, Rampal says. Multiple agents are in late phase 3 trials, and if data continue to prove positive for some or all of these treatments, there will be an influx of new treatment options entering clinical practice, Rampal notes.

Although the landscape will change, it remains unclear exactly how that will happen. One possible scenario is that trials for the drugs in development are successful, and then clinicians will need to determine if these treatments will be added on to current regimens for use in combinations, or if they should follow the use of JAK inhibitors if a patient does not have a full response, Rampal notes. These remain unanswered questions, but they will be addressed in short time as other agents begin to enter the treatment landscape, Rampal concludes.

Myelofibrosis Market to Witness Upsurge in Growth During the Forecast Period (2022-2032)

Posted on March 15, 2023March 15, 2023 by mpn_admin

Published March 13, 2023

The Myelofibrosis market is expected to surge due to the disease’s increasing prevalence and awareness during the forecast period. Furthermore, launching various multiple-stage Myelofibrosis pipeline products will significantly revolutionize the Myelofibrosis market dynamics.

DelveInsight’s “Myelofibrosis Market Insights, Epidemiology, and Market Forecast-2032″ report offers an in-depth understanding of the Myelofibrosis, historical and forecasted epidemiology as well as the Myelofibrosis market trends in the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom) and Japan.

The Myelofibrosis market report covers emerging drugs, current treatment practices, market share of the individual therapies, and current & forecasted market size from 2019 to 2032. It also evaluates the current treatment practice/algorithm, market drivers & barriers, and unmet medical needs to curate the best of the opportunities and assess the underlying potential of the market.

Myelofibrosis Overview

Myelofibrosis (MF) is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar like material. It is classified as a type of chronic leukemia and belongs to a group of blood disorders called myeloproliferative diseases.

Some of the key facts of the Myelofibrosis Market Report:

The Myelofibrosis market size is anticipated to grow with a significant CAGR during the study period (2019-2032)
In June 2022, Sierra Oncology submitted an NDA to the US FDA for momelotinib to treat myelofibrosis. The FDA has accepted the NDA and has assigned a PDUFA date of 16 June 2023
Vonjo, approved by the US FDA on February 28, 2022, is a kinase inhibitor used for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L
In various studies of European countries, annual prevalence of Myelofibrosis ranged from 0.5–9 cases per 100,000 individuals
Myelofibrosis is a disease that tends to affect the middle-aged and elderly population with a mean age of 60 years at diagnosis. Males are more commonly affected than females. In younger children, girls are affected twice as often as boys
The total prevalent population of myelofibrosis in the 7MM comprised of 39,735 cases in2021and is projected to increase during the study period (2019–2032)
In 2021, the highest number of prevalent cases were observed in the US. The total prevalent population of myelofibrosis in the US is 19,815 in 2021 and is projected to increase during the forecast period (2022-2032)
Key Myelofibrosis Companies: Pharmaxis, Keros Therapeutics, Bristol-Myers Squibb, Ascentage Pharma Group Inc., Sumitomo Pharma Oncology, Galecto Biotech AB, Actuate Therapeutics Inc, Karyopharm Therapeutics Inc, AbbVie, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Taiga Biotechnologies, Inc., Rigel Pharmaceuticals, Celgene, Novartis Pharmaceuticals, Sierra Oncology, Inc., Incyte Corporation, Imago BioSciences, Inc., Samus Therapeutics, Inc., Constellation Pharmaceuticals, Kartos Therapeutics, Inc., NS Pharma, Inc., Nippon Shinyaku Co., Ltd., Geron Corporation, Inc., Suzhou Zelgen Biopharmaceuticals Co.,Ltd, Hoffmann-La Roche, Lynk Pharmaceuticals Co., Ltd, Chengdu Zenitar Biomedical Technology Co., Ltd, Prelude Therapeutics, Cellenkos, Jacobio Pharmaceuticals, Active Biotech, The Menarini Group, Cyclica Inc, GAT Therapeutics, Hinova pharmaceuticals, iOnctura, Telios Pharma, Inc., and others
Key Myelofibrosis Therapies: Momelotinib, Navitoclax, Parsaclisib, Reblozy, Pelabresib, PXS-5505, and others

Key benefits of the Myelofibrosis Market report:

Myelofibrosis market report covers a descriptive overview and comprehensive insight of the Myelofibrosis Epidemiology and Myelofibrosis market in the 7MM (the United States, EU5 (Germany, Spain, France, Italy, UK) & Japan.)
The Myelofibrosis market report provides insights on the current and emerging therapies.
Myelofibrosis market report provides a global historical and forecasted market covering drug outreach in 7MM.
The Myelofibrosis market report offers an edge that will help develop business strategies by understanding trends shaping and driving the Myelofibrosis market.

Download the report to understand which factors are driving Myelofibrosis epidemiology trends @ Myelofibrosis Epidemiological Insights

Myelofibrosis Market

The dynamics of the Myelofibrosis market are anticipated to change in the coming years owing to the expected launch of emerging therapies and others during the forecasted period 2019-2032.

“According to the estimates, the highest market size of Myelofibrosis was found in theUnitedStates and the least was in Spain across the 7MM. Besides, the upcoming therapies of Myelofibrosis are expected to combat the current unmet needs faced by the patients with Myelofibrosis and add to the overall growth of the Myelofibrosis market size.”

Myelofibrosis Epidemiology

The epidemiology section provides insights into the historical, current, and forecasted epidemiology trends in the seven major countries (7MM) from 2019 to 2032. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. The epidemiology section also provides a detailed analysis of the diagnosed patient pool and future trends.

Myelofibrosis Epidemiology Segmentation:

The Myelofibrosis market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into:

Total Prevalence of Myelofibrosis
Prevalent Cases of Myelofibrosis by severity
Gender-specific Prevalence of Myelofibrosis
Diagnosed Cases of Episodic and Chronic Myelofibrosis

Myelofibrosis Drugs Uptake and Pipeline Development Activities

The drugs uptake section focuses on the rate of uptake of the potential drugs recently launched in the Myelofibrosis market or expected to get launched during the study period. The analysis covers Myelofibrosis market uptake by drugs, patient uptake by therapies, and sales of each drug.

Moreover, the therapeutics assessment section helps understand the drugs with the most rapid uptake and the reasons behind the maximal use of the drugs. Additionally, it compares the drugs based on market share.

The report also covers the Myelofibrosis Pipeline Development Activities. It provides valuable insights about different therapeutic candidates in various stages and the key companies involved in developing targeted therapeutics. It also analyzes recent developments such as collaborations, acquisitions, mergers, licensing patent details, and other information for emerging therapies.

Myelofibrosis Therapies and Key Companies

Momelotinib: Sierra Oncology
Navitoclax: AbbVie
Parsaclisib: Incyte
Reblozy: Celgene/Bristol Myers Squibb
Pelabresib: MorphoSys
PXS-5505: Pharmaxis

Myelofibrosis Market Strengths

Myelofibrosis is a rare form of hematologic cancer; thus, companies developing its treatment options can possess several advantages like market exclusivities, premium pricing, trial subsidy, and other benefits from the government bodies for R&D.

Dr. Mascarenhas on the Role of Pacritinib in Myelofibrosis

Posted on March 15, 2023March 15, 2023 by mpn_admin

Mar 8, 2023

John Mascarenhas, MD

John Mascarenhas, MD, professor of medicine, the Icahn School of Medicine, Mount Sinai, director, the Center of Excellence for Blood Cancers and Myeloid Disorders, member, the Tisch Cancer Institute, Mount Sinai, discusses the role of pacritinib (Vonjo) in patients with myelofibrosis.

Pacritinib is JAK1-sparing, JAK2, FLT3, IRAK1, and ACVR1 inhibitor used in the treatment of patients with myelofibrosis in the setting of cytopenias at full dose to obtain spleen and symptom benefit, Mascarenhas says. In February 2022, the FDA granted an accelerated approval to pacritinib 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.

The approval was based on data from the phase 3 PERSIST-1 (NCT01773187), phase 3 PERSIST-2 (NCT02055781), and phase 2 PAC203 (NCT04884191) trials, a dose-finding study, and the ongoing phase 3 PACIFICA trial (NCT03165734) is serving as a confirmatory trial following the agent’s accelerated approval, Mascarenhas expands.

Although pacritinib is approved for patients with platelets less than 50 × 109/L , PERSIST-2 also produced data in patients with a platelet count of less than 100 x 109/L. Prior to the approval of pacritinib, clinicians did not have a JAK2 inhibitor available for patients with a platelet count below that could be administered at the full dose, Mascarenhas notes. The JAK2 inhibitors fedratinib (Inrebic) and ruxolitinib (Jakafi) have labels patients with platelet counts of 50 × 109/L and greater. Since those two agents are more myelosuppressive, clinicians must attenuate the dose when treating patients with a platelet count below 50 × 109/L, reducing the spleen and symptom benefit generated by fedratinib and ruxolitinib, Mascarenhas says. Twenty 20 mg of pacritinib given twice daily can be delivered to patients with platelet counts at 20 × 109/or less and still produce spleen and symptom benefits with a favorable toxicity profile, Mascarenhas continues.

Studies have not demonstrated an increased risk of cardiovascular events with pacritinib, and data have shown reduced myelosuppression. There may be an increased risk of bleeding with pacritinib, and patients who have a known coagulopathy, have bleeding diathesis, or are receiving anticoagulation should be counseled appropriately, Mascarenhas expands. Although it is important consider the potential benefits and risks for each individual patient, pacritinib does provide an efficacious treatment option for patients with myelofibrosis with low platelet counts, Mascarenhas concludes.