ECLIPSE PV Trial Begins Ropeginterferon Alfa-2b Dosing in Polycythemia Vera

Posted on May 16, 2023May 16, 2023 by mpn_admin

May 15, 2023

Caroline Seymour

The first patients have been dosed in the phase 3b ECLIPSE PV trial, which is evaluating an accelerated dosing schedule of ropeginterferon alfa-2b-njft for the treatment of patients with polycythemia vera.

The first patients have been dosed in the phase 3b ECLIPSE PV trial (NCT05481151), which is evaluating an accelerated dosing schedule of ropeginterferon alfa-2b-njft (Besremi) using a prefilled syringe for the treatment of patients with polycythemia vera (PV).¹

“This therapy represents an important addition to the treatment arsenal for PV in the U.S., and clinical data support its use across a broad range of patients regardless of their treatment history,” John Mascarenhas, MD, professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai in New York, stated in a news release. “This new study is addressing an important therapeutic and clinical question regarding whether treatment utilizing accelerated dosing leads to a more rapid hematologic and molecular response, indicating potential disease modifying activity and long-term disease control.”

In November 2021, the FDA approved ropeginterferon alfa-2b for the treatment of patients with PV.² The agent is a novel monopegylated, long-acting interferon that can be administered once every 2 weeks, or every 4 weeks with hematological stability, for at least 1 year. The agent has the potential to produce durable activity through its pegylation technology.¹

The phase 3b study will evaluate an accelerated dosing schedule for ropeginterferon alfa-2b compared with the current labeled dosing.³ The primary end point of the study is the proportion of patients achieving a complete hematologic response at 24 weeks of treatment, defined as hematocrit below 45% for at least 3 months since last phlebotomy, platelets not exceeding 400 x 10⁹/L, and leukocytes of 10 x 10⁹/L or below.

The study, which will enroll approximately 100 patients with PV in the United States and Canada, will randomly assign patients to receive either the accelerated dosing or the current labeled dosing of 50 µg or 100 µg with 50 mcg titration every 2 weeks. Patients assigned to the accelerated dosing arm will receive a starting dose of 250 µg, then 350 µg at week 2, with a target optimal dose of 500 µg at week 4. Subsequent dosing will remain fixed at the highest tolerated dose for the rest of treatment.

The study will run for 48 weeks and will be followed by a 28-day period of safety follow-up. Patients who respond to treatment will be eligible to participate in a long-term extension phase of the study.

Topline data from the trial are expected by 2024.

“Our goal with this study is to deliver evidence on the potentially enhanced benefits of treating patients with ropeginterferon alfa-2b through this accelerated dosing schedule and to bring additional confidence to clinicians and patients in the utility of the treatment to manage this chronic cancer,” Raymond Urbanski, MD, PhD, U.S. head of Clinical Development and Medical Affairs, said in a news release. “We believe this study will deliver further insight into the potential of ropeginterferon alfa-2b to meet the needs of PV patients.”

References

PharmaEssentia initiates phase 3b trial of ropeginterferon alfa-2b-njft investigatng new dosing regimen for patients with polycythemia vera (PV). News release. May 3, 2023. Accessed May 15, 2023. https://us.pharmaessentia.com/wp-content/uploads/2023/05/ECLIPSE-PV_Initiation_Press_Release_May-3-2023-1.pdf
US FDA approves BESREMI (ropeginterferon alfa-2b-njft) as the only interferon for adults with polycythemia vera. News release. PharmaEssentia Corporation. November 12, 2021. Accessed May 15, 2023. https://us.pharmaessentia.com/wp-content/uploads/2021/11/BESREMi-FDA-Approval-November-12-2021.pdf
A study to assess efficacy, safety, and tolerability of P1101 in adult patients with PV. ClinicalTrials.gov. Updated March 27, 2023. Accessed May 15, 2023. https://clinicaltrials.gov/ct2/show/NCT05481151

Mesa Highlights JAK Inhibition for the Treatment of Myelofibrosis

Posted on May 16, 2023May 16, 2023 by mpn_admin

May 15, 2023

Jordyn Sava

In an interview, Ruben Mesa, MD, discussed the currently available JAK inhibitors for patients with myelofibrosis, and what is in store for the field.

JAK inhibitors have paved the way and improved clinical outcomes for patients with myeloproliferative neoplasms over the past decade. Not only have these agents shown significant improvements in efficacy outcomes, but they have demonstrated favorable safety profiles in this patient population.

Currently, 3 JAK inhibitors are approved for patients with myelofibrosis. The first was ruxolitinib (Jakafi), which was approved by the FDA in 2015 and continues to be the main therapy for patients with myelofibrosis. Patients treated with ruxolitinib have had improved splenomegaly and constitutional symptoms, as well as an observed survival benefit.

Following the approval of ruxolitinib came 2 more, including the JAK2 inhibitor fedratinib (Inrebic) which was approved in 2019, and pacritinib (Vonjo) in 2022. Studies of fedratinib have confirmed that the agent is a beneficial second-line treatment option for patients who are ruxolitinib-resistant. Pacritinib also continues to serve as a good treatment option for patients with myelofibrosis and severe thrombocytopenia.

Now, another JAK1/2 inhibitor is in clinical development, known as momelotinib, and is being evaluated in the phase 3 MOMENTUM trial (NCT04173494) for patients who are symptomatic and anemic with advanced myelofibrosis. Those enrolled in MOMENTUM must have previously been treated with a JAK inhibitor, and findings from the study already have revealed clinically significant improvements with momelotinib vs danazol in this patient population.

Data from the MOMENTUM study revealed that 25% of patients treated with momelotinib (n = 130) had a 50%, or more, reduction in patient’s Myelofibrosis Symptom Assessment Form Total Symptom Score (TSS) vs 9% of patients treated with danazol (n = 65), making a proportion difference of 16%. Researchers confirmed this difference to be statistically significant (95% CI, 6–26; P =.0095).

Now, the United States has assigned a Prescription Drug User Fee Act (PDUFA) action date of June 16, 2023.

“We are in an unprecedented period of excitement around new therapies for myeloproliferative neoplasms. Each response and benefit with JAK inhibitors showed a lot of great updated data, [including] momelotinib, which may be approved in 2023,” Ruben Mesa, MD, told Targeted Oncology^TM, in an interview.

In the interview, Mesa, director of the UT Health San Antonio MD Anderson Cancer Center, discussed the currently available JAK inhibitors for patients with myelofibrosis, and what is in store for the field.

Targeted Oncology: Can you discuss some of the approved JAK inhibitors in the myelofibrosis space?

Mesa: For myelofibrosis, we are excited to have 3 FDA-approved therapies, ruxolitinib, pacritinib, and fedratinib, that are all inhibitors of JAK2. Ruxolitinib is from 2011, fedratinib is from 2019, and pacritinib which [was approved in 2022]. Ruxolitinib and fedratinib are both approved in the frontline setting as well as fedratinib in the second-line setting. Now pacritinib is approved in the front and second-line settings for patients who have a platelet count of less than 50,000, and certainly, is a consideration for platelet counts under 100,000 or as a third-line in any patient. These have been a great help.

We have momelotinib coming up on the heels. That might become an approved therapy in 2023. We anticipate all these agents will hopefully improve spleen and symptoms. I think in responding patients, probably all will have a beneficial impact in terms of survival, and we’re excited to have these to build from in this space.

Can you explain the purpose behind the MANIFEST trial and the SIMPLIFY-1 study?

What the MANIFEST study was looking at was pelabresib [CPI-0610] in combination with ruxolitinib, either in the frontline or second-line setting. That was the goal, and we’ve been excited by the data that shows a good depth of response as a single agent with JAK inhibition, as well as potentially extending further the types of benefits that might be seen. That’s helped us to set up the MANIFEST-2 that is ongoing.

The MOMENTUM study, a different study, is [looking at] second-line therapy, symptomatic myelofibrosis with anemia, and showed that momelotinib is clearly superior compared with danazol. These data provide further study updates showing the durability of response screaming symptoms anemia. We are excited about this data.

What is the most new, exciting, and practice changing data in the myeloproliferative neoplasm space?

We are in an unprecedented period of excitement around new therapies for myeloproliferative neoplasms. Each response and benefit with JAK inhibitors showed a lot of great updated data, [including] momelotinib, which may be approved in 2023, as well as pacritinib and validating data with fedratinib. Combinations and phase 2 studies, whether with parsaclisib, venetoclax [Venclexta], pelabresib, or other combinations that may be coming, these combination therapies are truly the way of the future, so it is an exciting time.

AOP Health congratulates FROM on its great scientific work in the field of myeloproliferative neoplasms

Posted on May 16, 2023May 16, 2023 by mpn_admin

May 15, 2023 11:06 AM Eastern Daylight Time

VIENNA–(BUSINESS WIRE)–Fondazione per la Ricerca dell’Ospedale di Bergamo (FROM) announced the publication of the latest results from the LOW-PV trial in the NEJM Evidence.

The findings support a paradigm shift in the treatment of patients with Polycythaemia Vera, a rare kind of blood cancer. AOP Orphan Pharmaceuticals GmbH (AOP Health) congratulates Prof. Tiziano Barbui and his team on this success and is pleased to have contributed to FROM’s important work as a reliable research partner.

Find out more about the trial and its results here.

About AOP Health

The AOP Health Group incorporates several companies including AOP Orphan Pharmaceuticals GmbH with its seat in Vienna, Austria (“AOP Health”). The AOP Health Group is the European pioneer for integrated therapies for rare diseases and in critical care. Over the past 25 years, the Group has become an established provider of integrated therapy solutions operating from its headquarters in Vienna, its subsidiaries and representative offices throughout Europe and the Middle East, as well as through partners worldwide. The claim “Needs. Science. Trust.” sums up the foundation of the Group’s success: establishing trust through a continually high level of investment in research and development and a highly consistent and pragmatic orientation towards the needs of all stakeholders – especially the patients and their families as well as the healthcare professionals treating them.

A Patient Story: Don’t Make It More Difficult

Posted on May 15, 2023May 15, 2023 by mpn_admin

It has been said almost every family has been touched by cancer. I developed AML/APL Leukemia in 2006 and suffered a horrible reaction to chemo that kept me hospitalized for almost 5 months. It was a terribly difficult experience, but I made it through treatment and was so happy to reach the 5-year mark without other major issues. Then, in 2017, a routine physical found elevated platelets and white cells, a
huge red flag. Over the course of a short few months, the platelets rose to over one million. Anxiety followed me, closer than my shadow. Was AML back? Were chemo and hospitalization in my future? After a bone marrow biopsy, I was diagnosed with Essential Thrombocythemia.

For those living with illness, anxiety is simply a reality of life. We constantly scan our bodies for any sign of something wrong. We are nervous about blood test results because…what if…is always on our minds. Something bad happened to us and it made a physical memory we don’t want repeated. If illness has taught me anything, it is the importance of appreciating the present.

We have thousands of thoughts every day and most of them pass as background noise. The mind chatters away and we don’t engage with it too much. But let a scary thought come up, and we get carried away with worry that easily becomes all-consuming. What can be done?

Watch your focus. Treat disturbing thoughts as passing visitors. Let them come and go, and certainly don’t invite them in for tea and conversation. Instead, be present. Breathe deeply, relax your shoulders, and do something tactile. Gently change your focus to the here and now. Don’t chase upsetting thoughts, don’t play with them, chew on them, or try to block them out. Let them pass like clouds in the sky. There is no need to respond. You don’t have to react.

Experience has taught you life is short and can change in a moment. Absolutely everything is temporary. So, why are you wasting your precious time lost in thought, washed in worry? It really doesn’t help anything. You only have one precious life. Live it. Don’t wait. Do whatever you find interesting and rewarding. Your life will only have a deeper meaning when you do things that are meaningful to you.
Quit just getting by. You are so much more than your illness. Take charge. Don’t just survive – thrive.

Bob P.

Kishtagari Discusses Risk Assessment and Treatment Options in Myelofibrosis

Posted on May 15, 2023May 15, 2023 by mpn_admin

May 12, 2023

Targeted Oncology Staff

CASE

A 68-year-old man presented to his physician with symptoms of fatigue, drenching night sweats, abdominal pain, and intermittent fevers lasting 4 months. He also reported increased bruising.
Medical history: type 2 diabetes and atrial fibrillation, both controlled with medication
Spleen palpable 10 cm below the left costal margin
CT scan of the abdomen/pelvis showing splenomegaly with spleen length of 30.3 cm
ECOG performance status: 2

Targeted Oncology: What are the recommendations from the National Comprehensive Cancer Network (NCCN) guidelines in high-risk myelofibrosis?

KISHTAGARI: According to the NCCN guidelines, the symptom assessment score, based on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score [MPN-SAF TSS], is an important objective tool, which I always [use] in my practice to assess the symptom burden. Then you risk stratify these patients based on the platelet count. With a platelet count of less than 50,000/μL, we can treat with pacritinib [Vonjo], and the other option is a clinical trial.

Every patient with myelofibrosis needs to have a transplant evaluation. If a patient is a transplant candidate, they need to proceed with allogeneic hematopoietic cell transplant. With a platelet count of at least 50,000/μL, we can consider ruxolitinib [Jakafi] or fedratinib [Inrebic].¹ One thing I want to highlight, which is something the NCCN guidelines have clearly stated, is that if a patient [experiences progression] on ruxolitinib or fedratinib [and] is intolerant to [either], you can consider pacritinib even if the platelet count is 50,000/μL or more.¹ Even though it is only approved for patients with a platelet count of less than 50,000/μL in the front-line setting,² in the second-line setting, you can consider it for patients with a platelet count of 50,000/μL or more.¹

What therapeutic agents are approved by the FDA for the management of myelofibrosis?

Three agents are FDA approved for [managing] myelofibrosis. All 3 are JAK inhibitors, and there are slight differences in the way they work. The JAK2 mutation was discovered in this disease in 2005, and then there was a focus on inhibiting this mutation, and that led to the development of ruxolitinib. This was FDA approved in 2011 for the [management] of intermediate- or high-risk primary or secondary myelofibrosis.³

The recommended starting dosage of ruxolitinib, if the platelet count is more than 200,000/μL, is 20 mg twice a day. For a platelet count in the range of 100,000/μL to 200,000/μL, you initiate at 15 mg twice a day. For a platelet count in the range of 50,000/μL to less than 100,000/μL, it is recommended to initiate at 5 mg twice daily.⁴ This is something I do not recommend at all; 5 mg twice daily has never been shown to control symptom burden. I think these are patients for whom we need to consider [alternative] therapies. You can initiate it, but I have never seen any improvement at such a low dose of ruxolitinib. You need to monitor the complete blood count [every] 2 to 4 weeks until the dose is stabilized and then as clinically indicated.

What we struggle with in the clinic whenever we see these patients is [this]: If there is a drop in the platelet count, we decrease the dose of ruxolitinib. I do not recommend abruptly interrupting ruxolitinib because there is something called ruxolitinib withdrawal syndrome. Whenever you are trying to mitigate the thrombocytopenia, I think you need to reduce dose. That is probably a better strategy than stopping ruxolitinib altogether.

Fedratinib was approved in 2019 for intermediate-2 or high-risk primary or secondary myelofibrosis.⁵ It is approved for use at a dosage of 400 mg once a day for patients with a baseline platelet count of at least 50,000/μL. That platelet count was chosen because the patients with a platelet count of less than 50,000/μL had severe thrombocytopenia, [which] led to hemorrhage in the clinical trial.

That is the reason why only patients with a platelet count of at least 50,000/μL [should] get fedratinib. There are some dose reductions [recommended for patients who take strong CYP3A inhibitors] or who have renal impairment.⁶

Recently, pacritinib was FDA approved in 2022 for intermediate-or high-risk primary or secondary myelofibrosis in patients with a platelet count of less than 50,000/μL at a dosage of 200 mg twice a day,² with or without food.⁷

What symptoms of ruxolitinib withdrawal should physicians watch for?

The most important symptoms [are similar to those observed] when you suddenly stop steroids. Patients develop hypotension, severe rebound symptoms of their myelofibrosis, and a sudden drop in blood counts. All these point toward ruxolitinib withdrawal syndrome.

How do these 3 agents compare with each other?

Pacritinib, ruxolitinib, and fedratinib have slight differences in their mechanisms of action. The main thing I want to highlight is how pacritinib is different from the other 2 medications. Pacritinib does not inhibit JAK1; it only targets JAK2, in contrast with other medications.^8-10 It preferentially affects the JAK2 V617F mutation but does not affect JAK1,10 and JAK1 has been shown to play an important role in megakaryopoiesis.¹¹

One of the main reasons why this medication does not [cause a] drop in blood count is that it spares JAK1. Interestingly, it also inhibits IRAK1,¹⁰ and right now there is lot of clinical interest, [with respect to] myeloid [malignant tumors], to develop IRAK1 inhibitors because IRAK1 plays an important role in cytokine regulation. By inhibiting both JAK2 and IRAK1, pacritinib has a unique mechanism of action where it can control the symptom and help with the platelet count.

What clinical trials have examined the use of pacritinib in the management of cytopenic myelofibrosis?

There were 2 clinical trials: PERSIST-1 [NCT01773187] and PERSIST-2 [NCT02055781]. PERSIST-1 involved a 2:1 randomization to pacritinib at 400 mg once a day vs the best available therapy [BAT], and the classic primary end point was spleen volume reduction [SVR]. PERSIST-2 included patients [receiving either] first-line or second-line therapy, and they only included patients with a platelet count of no more than 100,000/μL. These were all patients with cytopenic myelofibrosis, an aggressive phenotype, and they were randomly assigned [1:1:1] to receive 400 mg once a day, 200 mg twice a day, or the BAT. This study had the classic end points of SVR at week 24 and the symptom assessment score based on the MPN-SAF TSS at week 24.¹²

What were the results of the PERSIST-2 trial?

In this clinical trial, there was a good distribution of patients who had already received ruxolitinib [45% in the control arm]. Additionally, some patients had received watch-and-wait [monitoring; 19%], some had received hydroxyurea [19%], and some had received steroids or other agents. There was a good distribution of both intermediate- and high-risk [disease] based on the Dynamic International Prognostic Scoring System classification [approximately 70% and 30%, respectively]. The majority of patients in the clinical trial had thrombocytopenia, and approximately 40% of patients had a platelet count of less than 50,000/μL. These patients were equally distributed between the twice-daily pacritinib arm and the BAT arm.¹² The SVR had a 35% cutoff at week 24. Pacritinib 200 mg twice a day improved the SVR compared with the BAT [SVR of at least 35% occurred in 18% vs 3% of patients in the twice-daily experimental arm and control arm, respectively].^7,12

Pacritinib also improved the total symptom [score and the individual symptom score]. These are the different measures we use in all clinical trials with myelofibrosis. [These are] based on the MPN-SAF TSS. Pacritinib decreased the symptom burden compared with the BAT arm [Patient Global Impression assessment scores of “much improved” or “very much improved” were observed in 57% vs 28% of the twice-daily experimental arm and control arm, respectively].¹²

The transfusion burden is very important clinically. Pacritinib 200 mg twice a day improved the transfusion burden by week 24 [among transfusion-dependent patients; the percentage of patients that experienced a reduced burden was 22% in the twice-daily experimental arm vs 9% in the control arm]. Pacritinib also [improved] hemoglobin levels and stabilized the transfusion burden if it was not improved.

What were the adverse events observed in this trial?

The most important adverse event I want to highlight is diarrhea, which was observed in 48% of patients in the twice-daily arm, but rarely was this grade 3 or higher [4%]. Whenever a patient experiences diarrhea, in my practice at least, they respond very well with a single dose of loperamide [Imodium]. You can try that, and if the patient has persistent diarrhea despite the medication, then you need to reduce dose. But in the clinical trial, rarely was the dose reduced.^7,12

Additionally, there was a good percentage of patients with thrombocytopenia [34% for all grades; 32% for grade 3 or higher] and anemia [24% for all grades; 22% for grade 3 or higher], but the majority of patients in the clinical trial had thrombocytopenia and anemia to begin with. For example, if a patient had a platelet count of 56,000/μL at the time of enrollment and they dropped to a platelet count of 49,000/μL, we know that is not clinically significant. However, the clinical trial would capture it as grade 3 thrombocytopenia.

Hematological Cancers Market Set to Witness Explosive Growth By 2031

Posted on May 15, 2023May 15, 2023 by mpn_admin

May 12, 2023

The global Hematological Cancers market research report is focuses on an overall consumption patterns, development trends, sales patterns and sales in key countries of the Hematological Cancers market. The report focuses on global Hematological Cancers vendors, marketing department and competition. This report also provides a detailed information on market share, new developments and business analysis, impact of domestic and major players, discusses the opportunities in terms of emerging size, revenue, expectation, changes in industry regulations, product analysis, decisions strategy, product launch in the market, technological innovation, expansion, geographical location in the market. This study shows that there is a dynamic change in the market when it comes to the benefit of local and regional competition for large companies.

It is aggregated on the basis of different dynamic aspects of industry study. The statistical report is compiled by applying primary and secondary research methodologies. Comprehensive Porter’s five analysis and SWOT analysis are also used to examine the strength, weaknesses, threats and opportunities of the market.

Market Segmentation

The global Hematological Cancers market is segmented on the basis of solution, industry, and end user. Based on solution, the Hematological Cancers market is segmented into component, services. On the basis of industry, the Hematological Cancers market is segmented into manufacturing, others. Based on end user, the Hematological Cancers market is segmented into consumer and enterprises. The global Hematological Cancers market report includes a detailed analysis of the segmentation of this industry by Types and Applications.

Dr Mascarenhas on the Background of the MANIFEST-2 Trial in Myelofibrosis

Posted on May 15, 2023May 15, 2023 by mpn_admin

May 11, 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 background of the phase 3 MANIFEST-2 trial (NCT04603495) investigating the combination of pelabresib (CPI-0610) and ruxolitinib (Jakafi) vs ruxolitinib plus placebo in patients with myelofibrosis who have not been previously treated with a JAK inhibitor.

Previously, the phase 1/2 MANIFEST trial (NCT02158858) evaluated pelabresib alone and in combination with ruxolitinib. In patients who previously received ruxolitinib, the combination produced suboptimal responses, including a spleen volume reduction of at least 35% (SVR35) at week 24 in 20% of patients, Mascarenhas begins. However, in JAK inhibitor–naïve patients, the combination produced a SVR35 at week 24 of 68%, showing that significantly more spleen volume reduction can be obtained with the combination than one would expect with single-agent ruxolitinib, Mascarenhas notes. In addition to improved SVR35 at week 24, the combination led to significant symptom burden improvement in patients who were not treated with a prior JAK inhibitor, Mascarenhas explains.

Additional correlative study data suggested that pelabresib plus ruxolitinib elicited changes in the bone marrow that may be indicative of a more pronounced effect on the level of the disease within the marrow. For example, a hallmark of myelofibrosis is the clustering of atypical megakaryocytes in a tight formation in the bone marrow; however, with the combination therapy, the distance between megakaryocytes increased, which also correlated with spleen volume reduction and symptom improvement, Mascarenhas says. Changes within the bone marrow suggest disease modification stemming from treatment with pelabresib plus ruxolitinib, Mascarenhas emphasizes.

The goal of MANIFEST-2 is to determine the true benefit of pelabresib plus ruxolitinib combination therapy over ruxolitinib monotherapy with a randomized, placebo-controlled study. The phase 3 trial is an ongoing in patients with intermediate- and high-risk myelofibrosis who are naïve to a JAK inhibitor. The results of this study are anticipated because they have the potential to shift the treatment paradigm of myelofibrosis, Mascarenhas concludes.

Ryvu Therapeutics to Present Clinical and Preclinical Data on RVU120 at the 2023 European Hematology Association Congress

Posted on May 15, 2023May 15, 2023 by mpn_admin

May 11, 2023 11:16 ET

Updated Clinical Data from the Ongoing Phase 1b Dose-Escalation Study of RVU120 in Patients with AML or High-Risk MDS Show Favorable Safety and Promising Signs of Efficacy
Poster Presentation to Highlight Synergistic Effects of RVU120 in Combination with Ruxolitinib in Myeloproliferative Neoplasms

KRAKOW, Poland, May 11, 2023 (GLOBE NEWSWIRE) — Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, today announced that updated safety and efficacy data from the Phase 1b dose-escalation study of RVU120 in patients with Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (HR-MDS) and nonclinical data of RVU120 in combination with JAK1/2 inhibitor Ruxolitinib (RUX) in myeloproliferative neoplasms will be presented at the Annual European Hematology Association (EHA) 2023 Hybrid Congress, taking place June 8-11 in Frankfurt, Germany.

“We are very pleased with the emerging safety and efficacy data from the ongoing Phase 1b dose-escalation trial in these heavily pre-treated AML and HR-MDS patients,” said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. “Until February 2023, treatment with single-agent RVU120 has led to complete remission in one patient, an increase of hemoglobin and platelets in four patients, and bone marrow blast reduction in five patients, including in a patient with TP53 double-hit. Based on these encouraging clinical benefits, favorable safety, and no dose-limiting toxicities, we continue to dose escalate RVU120 and anticipate a further increase of anti-leukemic and erythroid-stimulating activity at higher doses.”

Dr. Nogai continued, “In addition, our data suggest synergistic effects between RVU120 and RUX in myelofibrosis by demonstrating a significant reduction of disease manifestation in vivo. These data reinforce the potential emerging role of targeting both CDK8/19 and JAK1/2 in myeloproliferative neoplasms. We look forward to sharing our findings at this year’s EHA Congress and to the continued development of RVU120.”

Details on the poster presentations are as follows:

Abstract Title: “Preclinical and Clinical Signs of RVU120 Efficacy, a Specific CDK8/19 Inhibitor in DNMT3A Mutation Positive AML and HR-MDS”
Abstract Number: #P450
Session date and time: Friday, June 9, 18:00 – 19:00 CEST

The clinical abstract presents updated safety and efficacy results from the ongoing Phase 1b dose escalation study of RVU120 for relapsed/refractory AML and high-risk MDS (NCT04021368). Results from patients dosed up to 110 mg have shown a favorable safety profile of RVU120. At the data cut-off of February 28, 2023, 22 pts have been enrolled, and 10 out of 19 evaluable patients showed clinical benefit: 1 pt. with AML treated at 75 mg with CR, 3 pts with AML treated at 100 mg, and 1 pt. with HR-MDS at 75 mg with a significant increase of hemoglobin and platelets, 4 pts with adverse risk cytogenetics treated between 10 and 100 mg with a BM blast reduction and 1 pt. with AML, dosed at 110 mg, showing a BM blast reduction of 70% at the beginning of cycle 4. No DLTs were observed, and no study drug interruptions due to adverse drug reactions occurred. The data warrant further exploration of RVU120 in AML and HR-MDS, and enrollment is ongoing at 135 mg.

Abstract Title: “Combination JAK1/2 and CDK8/19 inhibition demonstrates enhanced efficacy in myeloproliferative neoplasms”
Abstract Number: #P986
Session date and time: Friday, June 9, 18:00 – 19:00 CEST

The presentation, prepared in collaboration with Prof. Raajit Rampal’s group from Memorial Sloan Kettering Cancer Center, includes the assessment of RVU120, a highly selective and potent CDK8/19 inhibitor in monotherapy and combination with Ruxolitinib (RUX), a JAK1/2 inhibitor for the treatment of myeloproliferative neoplasms (MPN). Treatment with RVU120 demonstrated single agent efficacy that could be further enhanced by a synergistic combination with RUX in MPN models, both in vitro and in vivo. Treatment with the combination of RUX and RVU120 resulted in significant reductions of disease manifestation – mutated cell fractions, WBC, splenomegaly, and megakaryocyte differentiation when compared to RUX alone. These data nominate CDK8/19 inhibition in combination with JAK1/2 inhibition as a potential novel therapeutic strategy in MPNs.

All abstracts are now available online and can be obtained from the conference site: https://ehaweb.org/.

About Ryvu Therapeutics  

Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel small-molecule therapies that address emerging targets in oncology. Internally discovered pipeline candidates make use of diverse therapeutic mechanisms driven by emerging knowledge of cancer biology, including small molecules directed at kinase, synthetic lethality and immuno-oncology targets.

Ryvu’s most advanced programs are RVU120 — a selective CDK8/CDK19 kinase inhibitor with potential for the treatment of hematological malignancies and solid tumors currently in phase I clinical development for the treatment of acute myeloid leukemia and myelodysplastic syndrome, and phase I/II for the treatment of r/r metastatic or advanced solid tumors — and SEL24 (MEN1703), a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group, currently in phase II clinical studies in acute myeloid leukemia. In addition, Ryvu Therapeutics has signed multiple partnering and licensing deals with global companies, including BioNTech, Exelixis, , and Merck.

The Company was founded in 2007 and is headquartered in Kraków, Poland. Ryvu is listed on the Warsaw Stock Exchange and is a component of the sWIG80 index. For more information, please see www.ryvu.com.

MorphoSys Highlights Potential of Its Mid- to Late-Stage Oncology Pipeline at 2023 ASCO and EHA Annual Meetings

Posted on May 15, 2023May 15, 2023 by mpn_admin

Planegg/Munich, Germany, May 11, 2023

MorphoSys Highlights Potential of Its Mid- to Late-Stage Oncology Pipeline at 2023 ASCO and EHA Annual Meetings

MorphoSys AG (FSE: MOR; NASDAQ: MOR) today announced that the latest data on multiple pipeline therapies will be presented during the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois from June 2 to 6, 2023 and at the European Hematology Association (EHA) Hybrid Congress in Frankfurt, Germany from June 8 to 11, 2023. Presentations will include data on pelabresib, an investigational BET inhibitor; tafasitamab, a CD19-targeting immunotherapy, marketed in the U.S. in partnership with Incyte as Monjuvi^® and outside the U.S. by Incyte as Minjuvi^®; and tulmimetostat, an investigational next-generation dual inhibitor of EZH2 and EZH1.

“With pelabresib, we have the near-term potential to improve the standard of care for patients with myelofibrosis and the opportunity to expand into other myeloid diseases where new treatment options are still needed,” said Tim Demuth, M.D., Ph.D., MorphoSys Chief Research and Development Officer. “The data we are presenting at ASCO and EHA showcase the breadth and depth of our mid- to late-stage pipeline. We are committed to addressing the critical needs of patients with blood cancers, including myeloid malignancies, and those with solid tumors.”

Pelabresib is being investigated in the Phase 2 MANIFEST study in patients with myelofibrosis and essential thrombocythemia and in the Phase 3 MANIFEST-2 study in combination with ruxolitinib as a first-line treatment for myelofibrosis. Myelofibrosis and essential thrombocythemia are both myeloproliferative neoplasms, which are types of blood cancers that begin with a genetic change in bone marrow stem cells. The presentations on pelabresib include:

An oral presentation at EHA and a poster discussion at ASCO on new preliminary results from MANIFEST Arm 4 exploring pelabresib as a monotherapy in patients with high-risk essential thrombocythemia who are refractory or intolerant to hydroxyurea, the chemotherapeutic agent most used to treat the disease.
A poster presentation at EHA showcasing clinical data from MANIFEST Arm 3 evaluating pelabresib in combination with ruxolitinib for the treatment of patients with myelofibrosis who had not previously been treated with a JAK inhibitor (previously presented at American Society of Hematology [ASH 2022] Annual Meeting and Exposition).
A poster presentation at EHA with clinical data from MANIFEST Arm 2 evaluating pelabresib as add-on therapy to ruxolitinib in myelofibrosis patients with a suboptimal response or disease progression following treatment with ruxolitinib (previously presented at ASH 2022).

Monjuvi in combination with lenalidomide was investigated in the Phase 2 L-MIND study in patients with relapsed or refractory diffuse large B-cell lymphoma. The presentations on Monjuvi include:

A poster presentation at EHA of final five-year efficacy and safety data from L-MIND (previously presented at American Association for Cancer Research Annual Meeting 2023).
An e-publication at ASCO and EHA of a new five-year sub-group analysis from L-MIND.

Tulmimetostat is being evaluated in a Phase 1/2 trial in patients with advanced solid tumors or lymphomas, including ARID1A-mutated ovarian clear cell carcinoma and endometrial carcinoma, BAP1-mutated mesothelioma, and peripheral T-cell lymphoma. Tulmimetostat was designed to improve on first-generation EZH2 inhibitors through increased potency, longer residence time on target and a longer half-life, offering the potential for enhanced anti-tumor activity.

At ASCO, preliminary results from the Phase 2 portion of the study evaluating tulmimetostat across multiple tumor types will be presented during a poster session.

ASCO Abstract Titles	Session Type	Abstract Number	Presentation Date/Time
Pelabresib (CPI-0610) Monotherapy in High-Risk Essential Thrombocythemia Refractory or Intolerant to Hydroxyurea: Preliminary Results From MANIFEST Study	Poster Discussion	7019	June 5, 12:30 PM – 2:00 PM ET / 6:30 PM – 8:00 PM CEST
EZH2/EZH1 Inhibitor Tulmimetostat (CPI-0209) in Patients with Advanced Solid Tumors or Hematologic Malignancies: Preliminary Phase 2 Results	Poster	3094	June 3, 9:00 AM – 10:00 AM ET / 3:00 PM – 5:00 PM CEST
Five-year Subgroup Analysis of Tafasitamab + Lenalidomide from the Phase II L-MIND Study in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma	E-Publication	E19522	N/A

EHA Abstract Titles	Session Type	Abstract Number	Presentation Date/Time
Pelabresib (CPI-0610) Monotherapy in Patients With High-Risk Essential Thrombocythemia Refractory or Intolerant to Hydroxyurea: Preliminary Results From MANIFEST Study	Oral	S168	June 9, 9:30 AM – 9:45 AM ET / 3:30 PM – 3:45 PM CEST
Updated Durability of Response and Safety in MANIFEST Arm 3: Pelabresib (CPI-0610) Combined With Ruxolitinib for JAK Inhibitor Treatment-Naïve Patients With Myelofibrosis	Poster	P1027	June 9, 12:00 PM – 1:00 PM ET / 6:00 PM – 7:00 PM CEST
Updated Results From MANIFEST Arm 2: Efficacy and Safety of Pelabresib (CPI-0610) as Add-on to Ruxolitinib in Myelofibrosis	Poster	P1018	June 9, 12:00 PM – 1:00 PM ET / 6:00 PM – 7:00 PM CEST
Five-year Efficacy and Safety of Tafasitamab in Patients with Relapsed or Refractory DLBCL: Final Results from the Phase II L-MIND Study	Poster	P1138	June 9, 12:00 PM – 1:00 PM ET / 6:00 PM – 7:00 PM CEST
Five-year Subgroup Analysis of Tafasitamab + Lenalidomide from the Phase II L-MIND Study in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma	E-Publication	PB2304	N/A

Please refer to the ASCO 2023 online program and EHA 2023 online program for full session details and data presentation listings.

About MorphoSys

At MorphoSys, we are driven by our mission: More life for people with cancer. As a global commercial-stage biopharmaceutical company, we develop and deliver innovative medicines, aspiring to redefine how cancer is treated. MorphoSys is headquartered in Planegg, Germany, and has its U.S. operations anchored in Boston, Massachusetts. To learn more, visit us at www.morphosys.com and follow us on Twitter and LinkedIn.

About Pelabresib
Pelabresib (CPI-0610) is an investigational selective small molecule designed to promote anti-tumor activity by inhibiting the function of bromodomain and extra-terminal domain (BET) proteins to decrease the expression of abnormally expressed genes in cancer. Pelabresib is being investigated as a treatment for myelofibrosis and has not yet been evaluated or approved by any regulatory authorities.

About MANIFEST
MANIFEST (NCT02158858) is an open-label Phase 2 clinical trial of pelabresib in patients with myelofibrosis.

The MANIFEST trial is evaluating pelabresib in combination with ruxolitinib in JAK-inhibitor-naïve myelofibrosis patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline (SVR35) after 24 weeks of treatment. The trial is also evaluating pelabresib either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1) or as add-on therapy in combination with ruxolitinib in patients with a suboptimal response to ruxolitinib or myelofibrosis progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on transfusion-dependent (TD) status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to transfusion independence for 12 consecutive weeks. The primary endpoint for patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment. The study is also evaluating pelabresib as a monotherapy in patients with high-risk essential thrombocythemia who are intolerant of, or refractory to, hydroxyurea (Arm 4). The primary endpoint for patients in Arm 4 is complete hematological response rate after one cycle, or 21 days, of treatment. Constellation Pharmaceuticals, Inc., a MorphoSys company, is the MANIFEST trial sponsor.

About MANIFEST-2

MANIFEST-2 (NCT04603495) is a global, double-blind, randomized Phase 3 clinical trial with pelabresib in combination with ruxolitinib versus placebo plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis. The primary endpoint of the study is a 35% or greater reduction in spleen volume (SVR35) from baseline at 24 weeks. The key secondary endpoint of the study is a 50% or greater improvement in total symptom score (TSS50) from baseline at 24 weeks. Constellation Pharmaceuticals, Inc., a MorphoSys company, is the MANIFEST-2 trial sponsor.

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody. 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 the EU.

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

Important Safety Information

What are the possible side effects of MONJUVI?

MONJUVI may cause serious side effects, including:

Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get fever, chills, rash, flushing, headache, or shortness of breath during an infusion of MONJUVI.
Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or any bruising or bleeding.
Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or develop any signs and symptoms of an infection.

The most common side effects of MONJUVI include:

Feeling tired or weak
Diarrhea
Cough
Fever
Swelling of lower legs or hands

Respiratory tract infection
Decreased appetite

These are not all the possible side effects of MONJUVI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you:

Have an active infection or have had one recently.
Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.

You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.

Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.

You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Please see the full Prescribing Information for Monjuvi, including Patient Information, for additional Important Safety Information.

About L-MIND

The L-MIND trial was a single arm, open-label Phase 2 study (NCT02399085) investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma who had at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or refused subsequent autologous stem cell transplant. The study’s primary endpoint was overall response rate. Secondary outcome measures included duration of response, progression-free survival and overall survival. In May 2019, the study reached its primary completion.

About Tulmimetostat

Tulmimetostat (CPI-0209) is an investigational compound designed to exert anti-tumor activity by inhibiting the function of enhancer of zeste homolog 1 and 2 (EZH2 and EZH1) proteins to reactivate silenced genes like tumor suppressor genes. Tulmimetostat is being tested as a once-daily oral treatment in a Phase 1/2 trial (NCT04104776) in patients with advanced solid tumors or lymphomas, including ARID1A-mutated ovarian clear cell carcinoma and endometrial carcinoma, diffuse large B-cell lymphoma, peripheral T-cell lymphoma, BAP1-mutated mesothelioma and castration-resistant prostate cancer. The primary outcome measures include frequency of dose-limiting toxicities, maximum tolerate dose and overall response rate.

Forward Looking Statements

This communication contains certain forward-looking statements concerning the MorphoSys group of companies. The forward-looking statements contained herein represent the judgment of MorphoSys as of the date of this release and involve known and unknown risks and uncertainties, which might cause the actual results, financial condition and liquidity, performance or achievements of MorphoSys, or industry results, to be materially different from any historic or future results, financial conditions and liquidity, performance or achievements expressed or implied by such forward-looking statements. In addition, even if MorphoSys’ results, performance, financial condition and liquidity, and the development of the industry in which it operates are consistent with such forward-looking statements, they may not be predictive of results or developments in future periods. Among the factors that may result in differences are that MorphoSys’ expectations may be incorrect, the inherent uncertainties associated with competitive developments, clinical trial and product development activities and regulatory approval requirements, MorphoSys’ reliance on collaborations with third parties, estimating the commercial potential of its development programs and other risks indicated in the risk factors included in MorphoSys’ Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. MorphoSys expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements, unless specifically required by law or regulation.

Dr Jain on Baseline Differences Across Different Donor Types in Myelofibrosis

Posted on May 15, 2023May 15, 2023 by mpn_admin

May 10, 2023

Tania Jain, MBBS

Tania Jain, MBBS, director, Adult Chimeric Antigen Receptor T-cell Therapy Program for Hematological Malignancies, Sidney Kimmel Comprehensive Cancer Center, assistant professor of oncology, Johns Hopkins Medicine, discusses notable differences in baseline characteristics and donor sequencing, according to a retrospective study of patient outcomes following blood or marrow transplant in 4 common donor types of myelofibrosis.

This real-world retrospective study compared the outcomes of 4 common donor types in myelofibrosis. Data from 1057 adult patients who underwent a first allogenic stem cell transplant (allo-SCT) using a peripheral blood graft between 2013 and 2019 for chronic phase myelofibrosis were obtained from the CIBMTR and the CIBMTR is a working group of over 500 BMT centers. Patients had either a matched sibling donor (MSD), matched unrelated (MUD) donor, mismatched unrelated donor (MMUD), or a haploidentical donor (HD) with posttransplant cyclophosphamide.

Notable differences were observed at baseline in the study population, Jain begins. As expected, a majority of MSD, MUD and MMUD patients were White, she says. Specifically, about 40% of HD donors were of non-White ethnicities. This demographic breakdown is relevant to note, as recently published data have shown a difference in transplant outcomes in patients of non-White ethnicities, Jain explains. This discrepancy may not be solely attributable to socioeconomic factors, and could be influenced by biological factors, she says.

Furthermore, sequencing donor selection in clinic is different than that of clinical trials, Jain continues. Typically, MSDs are the preferred donor option for patients with myelofibrosis. If no MSDs can be identified, the search will expand to MUD, followed by the other 2 donor types. However, research has shown that it takes longer to identify a HD vs a MSD, Jain reports. This practical limitation often results in a longer delay in transplant for patients waiting for an MMUD or HD, she states.

Findings from the study showed that HD and posttransplant cyclophosphamide is a viable alternative to MUD for patients requiring allo-SCT who cannot find a MSD. These results indicate that this delay in transplant is not necessary for these patients, Jain says. Additionally, HDs are more readily available, and may be more affordable for some patients, she concludes.