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

Posted on by

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.

Read more

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

Posted on by

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.

Read more

Dr Jain on Baseline Differences Across Different Donor Types in Myelofibrosis

Posted on by

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.

Read more

High Frequencies of Myeloid-Derived Suppressor Cells Seen in Patients With Myeloproliferative Neoplasms

Posted on by

May 10, 2023

Vicki Morre, PhD

A study involving patients with myeloproliferative neoplasms (MPNs) revealed high frequencies of myeloid-derived suppressor cells (MDSCs) in bone marrow. The study findings were reported in the journal Advances in Molecular Pathology.

In their report, the study investigators explained that while MDSCs have been shown to be more frequent in the peripheral blood of patients with MPNs, the frequency of these in the bone marrow had not been well understood.

In this study, they evaluated the frequencies of MDSCs in the peripheral blood and bone marrow of patients with MPNs and correlated these levels with other clinical and laboratory parameters.

Overall, 64 patients with MPNs were included in the study. For bone marrow analyses, the study recruited 17 patients with essential thrombocythemia (ET), 29 patients with polycythemia vera (PV), and 18 patients with primary myelofibrosis (PMF), in addition to 5 healthy donors. Analyses of peripheral blood included 11 patients with ET, 11 patients with PV, 9 patients with PMF, and 11 donors without hematologic malignancies.

Included patients had been previously untreated, and multiple clinical and laboratory parameters, including JAK2 and CALR variant status, were obtained from them at the time of diagnosis. MDSCs were evaluated through flow cytometry, and other assays were also performed.

Median ages were 56 years for patients with ET, 60 years for patients with PV, and 62 years for patients with PMF. Assays showed that in the bone marrow percentages of total MDSCs (T-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) were significantly greater across patients with MPNs than in healthy donors.

These differences were greatest for patients with PMF, who had a mean T-MDSC level of 55.37%, compared with healthy donors, who had a mean T-MDSC level of 25.36% (P =.004). The mean PMN-MDSC level was 54.58% for patients with PMF, compared with 18.8% for healthy donors (P =.008), as well.

Peripheral blood analyses also showed significant elevations in T-MDSC and PMN-MDSC levels in patients with MPNs, compared with healthy donors, apart from a trend of moderately higher percentage of circulating T-MDSCs in patients with ET that did not reach significance.

There were, however, not correlations seen between elevated MDSCs in the bone marrow and parameters of age, hepatomegaly, leukocytes, hemoglobin, or platelet levels. JAK2 or CALR status also appeared uncorrelated with MDSC levels.

The study investigators reported an additional finding of an apparent immunosuppressive function of MDSCs from patients with MPNs. In patient samples that had undergone MDSC depletion, T-cell proliferation rates were significantly higher than they were without MDSC depletion, across MPN types.

“In summary, this study demonstrated increased frequency levels of MDSCs in the bone marrow of MPNs patients,” the investigators wrote in their report. Although MDSC levels did not show correlations with multiple clinical parameters or with mutations of JAK2 or CALR genes, the investigators pointed out myelofibrosis intensity appeared associated with MDSC frequency in bone marrow.

Reference

Kapor S, Momčilovič S, Kapor S, et al. Increase in frequency of myeloid-derived suppressor cells in the bone marrow of myeloproliferative neoplasm: potential implications in myelofibrosis. Adv Exp Med Biol. 2023;1408:273-290. doi:10.1007/978-3-031-26163-3_15

Read more

Sobi to acquire CTI BioPharma Corp. enhancing Sobi’s position in rare haematology

Posted on by

NOT FOR RELEASE, PUBLICATION OR DISTRIBUTION, IN WHOLE OR IN PART, IN, INTO OR FROM ANY JURISDICTION WHERE TO DO SO WOULD CONSTITUTE A VIOLATION OF THE RELEVANT LAWS OR REGULATIONS OF THAT JURISDICTION. THIS PRESS RELEASE DOES NOT CONSTITUTE AN OFFER OF OR THE SOLICITATION OF AN OFFER TO BUY SECURITIES IN ANY JURISDICTION.

Swedish Orphan Biovitrum AB (publ) (Sobi®) (STO:SOBI) today announced that it has entered into an agreement and plan of merger with CTI BioPharma Corp. (CTI) under which Sobi has agreed to acquire CTI, a biopharmaceutical company focused on blood related cancers and rare diseases, by means of a tender offer.

The acquisition complements and further strengthens Sobi’s leading haematology franchise by adding VONJO® (pacritinib), a novel oral kinase inhibitor that inhibits JAK2, IRAK1 and ACRV1, while sparing JAK1. VONJO obtained accelerated approval by the FDA in February 2022 for 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.

Rationale of the acquisition and transaction in brief:

  • Adds VONJO, a differentiated product in the treatment of myelofibrosis, specifically addressing patients with severe thrombocytopenia, an unmet medical need.
  • Highly complementary to Sobi’s existing portfolio, specifically Doptelet®, expands Sobi’s leading position in rare haematology and accelerates access for patients to both therapies globally.
  • Both VONJO and Doptelet address rare haematological platelet disorders and are prescribed by haemato-oncologists and haematologists. The acquisition accelerates Sobi’s strategy to build a leading franchise in rare haematology.
  • The addition of VONJO brings a uniquely differentiated therapy, serving an unmet medical need for patients suffering from myelofibrosis.
  • The acquisition is expected to accelerate Sobi’s revenue growth, and to improve margins, adding a commercial-stage asset in the U.S., with the potential for further expansion globally.
  • Sobi to commence a cash tender offer to acquire all issued and outstanding shares of CTI for USD 9.10 per share, corresponding to a total equity value of USD 1.7 billion (approximately SEK 17.1 billion).
  • Fully funded through committed debt financing, up to half of which is anticipated to be refinanced through a rights issue after the closing of the acquisition, with a commitment from Investor AB to subscribe for its pro rata share of the rights issue, corresponding to approximately 34.7% of the shares to be issued in the rights issue.

“CTI represents a perfect fit for Sobi’s haematology franchise today, adding a powerful and highly differentiated new product that will make a significant difference for patients”, said Guido Oelkers President and CEO of Sobi. “There is a large unmet medical need within myelofibrosis, in particular for patients suffering from thrombocytopenia who are inadequately treated by existing medicines. The combination of the talented team at CTI, together with Sobi’s broad US and global haematology capabilities, will help get this much needed new therapy to patients faster and more effectively. The acquisition of CTI is the latest in a series of transformative transactions Sobi has conducted to build its leading rare haematology franchise.”

Financial highlights

The acquisition is expected to be highly accretive to Sobi’s revenue and margins, starting in the near-term.  Revenue and cost synergies are expected from leveraging the highly complementary nature of Sobi’s existing U.S. commercial operations and global sales infrastructure in haematology and rare diseases.

Sobi has obtained committed debt financing from Bank of America and Danske Bank. Sobi anticipates that up to half of the merger consideration will be refinanced through an issuance of new ordinary shares of Sobi with preferential rights for existing shareholders of Sobi, after the closing of the acquisition.

Sobi’s main shareholder, Investor AB, has undertaken to vote in favor of the implementation of the rights issue at an extraordinary general meeting. Investor AB has also undertaken to subscribe for its pro rata share of the rights issue, corresponding to approximately 34.7% of the shares to be issued in the rights issue. A detailed time plan and the forms for the implementation of the rights issue will be announced at a later stage.

Transaction details

Under the terms of the merger agreement, Sobi, through a wholly owned, indirect subsidiary, will initiate a tender offer to acquire all the outstanding shares of CTI for a cash purchase price of USD 9.10 per share, representing a premium of 95% based on CTI’s 30-day volume-weighted average price of USD 4.67 preceding announcement of the transaction price of USD 9.10. The Board of Directors of CTI has unanimously approved the transaction and recommended that the shareholders of CTI tender their shares in the tender offer. Sobi has received an irrevocable undertaking from certain entities affiliated with BVF Partners L.P. (BVF) to tender all of their common shares, representing 6.7% of all outstanding common shares.

The closing of the tender offer will be subject to customary conditions, including the tender of shares which represent at least a majority of the total number of CTI’s outstanding common shares and the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act. Upon the successful completion of the tender offer, Sobi would acquire any shares of CTI’s common stock not tendered through a second-step merger effected for the same per common share consideration. The transaction is expected to close in Q3 2023.

 Advisors

Bank of America Europe DAC, Stockholm branch (“BofA Securities”) is acting as Sobi’s exclusive financial advisor in connection with the transaction and Latham & Watkins LLP is acting as legal advisor to Sobi on this transaction. Mannheimer Swartling is acting as legal advisor to Sobi in relation to the debt financing and rights issue.

About VONJO

VONJO is approved 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. This indication is approved under FDA accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). CTI is conducting the Phase 3 PACIFICA study of VONJO in patients with myelofibrosis and severe thrombocytopenia as a post-marketing requirement. For more information, please visit https://www.ctibiopharma.com.

 About CTI

CTI is a commercial biopharmaceutical company focused on the development and commercialization of novel targeted therapies for blood-related cancers that offer a unique benefit to patients and their healthcare providers. CTI has one FDA-approved product, VONJO® (pacritinib), a JAK2, ACVR1, and IRAK1 inhibitor, that spares JAK1. CTI is based in Seattle, USA, and has approximately 144 employees. In 2022, CTIs revenue amounted to USD 53.9 million.  For more information, please visit www.ctibiopharma.com.

Important information

The tender offer for the outstanding shares of CTI common stock referenced in this press release has not yet commenced. This document is for informational purposes only and it is neither an offer to purchase nor a solicitation of an offer to sell shares of CTI’s common stock, nor is it a substitute for the tender offer materials that Sobi and Cleopatra Acquisition Corp., a Delaware corporation and indirect, wholly owned subsidiary of Sobi (“Purchaser”) will file with the United States Securities and Exchange Commission (the “SEC”), upon commencement of the tender offer. At the time any such tender offer is commenced, Sobi and Purchaser will file a tender offer statement on Schedule TO, containing an offer to purchase, a form of letter of transmittal and other related tender offer documents with the SEC, and CTI will file a Solicitation/Recommendation Statement on Schedule 14D-9 relating to such tender offer with the SEC. CTI’s stockholders are strongly advised to read these tender offer materials carefully and in their entirety when they become available, as they may be amended from time to time, because they will contain important information about such tender offer that CTI’s stockholders should consider prior to making any decisions with respect to such tender offer. Once filed, stockholders of CTI will be able to obtain a free copy of these documents at the website maintained by the SEC at www.sec.gov. or on CTI’s website at https://www.ctibiopharma.com.

The press release is for informational purposes only and does not constitute an offer to sell or issue, or the solicitation of an offer to buy or acquire, or subscribe for, any securities in Sobi mentioned herein (collectively, the “Securities”) or any other financial instruments in Sobi. Any offer in respect of any Securities will only be made through the prospectus that Sobi expects to publish in due course. Offers will not be made to, and application forms will not be approved from, subscribers (including shareholders), or persons acting on behalf of subscribers, in any jurisdiction where applications for such subscription would contravene applicable laws or regulations, or would require additional prospectuses, filings, or other measures in addition to those required under Swedish law. Measures in violation of the restrictions may constitute a breach of relevant securities laws.

No Securities have been or will be registered under the United States Securities Act of 1933, as amended (the “Securities Act”), or the securities laws of any state or other jurisdiction in the United States, and may not be offered, pledged, sold, delivered or otherwise transferred, directly or indirectly, except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and in compliance with applicable other securities laws. There will not be any public offering of any Securities in the United States.

This announcement does not constitute an investment recommendation. The price and value of securities and any income from them can go down as well as up and investors could lose their entire investment. Past performance is not a guide to future performance. Information in this announcement cannot be relied upon as a guide to future performance.

Forward-looking statements

This press release contains forward-looking statements by Sobi that involve risks and uncertainties and reflect Sobi’s judgment as of the date of this press release. These forward-looking statements generally are identified by words such as “believe,” “project,” “expect,” “anticipate,” “estimate,” “intend,” “strategy,” “future,” “opportunity,” “plan,” “may,” “should,” “will,” “would,” and similar expressions. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. These forward-looking statements include, without limitation, statements regarding: the timing of the anticipated acquisition and when and whether the anticipated acquisition ultimately will close; the potential contributions the acquisition is expected to bring to Sobi; and the expected impact on Sobi’s future financial and operating results. Actual events or results may differ from Sobi’s expectations due to risks and uncertainties inherent in Sobi’s business, including, without limitation: the risk that the conditions to the closing of the transaction are not satisfied, including the risk that Sobi may not receive sufficient number of shares tendered from CTI’s stockholders to complete the tender offer; litigation relating to the transaction; uncertainties as to the timing of the consummation of the transaction and the ability of each of Sobi, Purchaser or CTI to consummate the transaction; risks that the proposed transaction disrupts the current plans and operations of Sobi or CTI; the ability of CTI to retain key personnel; competitive responses to the proposed transaction; unexpected costs, charges or expenses resulting from the transaction; potential adverse reactions or changes to business relationships resulting from the announcement or completion of the transaction; Sobi’s ability to achieve the growth prospects and synergies expected from the transaction, as well as delays, challenges and expenses associated with integrating CTI with its existing businesses; legislative, regulatory and economic developments; and other risks described in Sobi’s prior press releases. These forward-looking statements are made only as of the date hereof and Sobi disclaims any intent or obligation to update these forward-looking statements after the date hereof, except as required by law.

Invitation to conference call

Following the announcement of the acquisition, investors, analysts and media are invited to participate in a conference call which will include a presentation and a Q&A session today, 10 May at 15:00 CEST. The event will be hosted by Sobi’s President and CEO, Guido Oelkers, and the presentation will be held in English. The presentation can be followed live or afterwards on sobi.com. The slides will be made available on sobi.com.

To participate in the conference call, please use the following dial-in details:

Sweden: +46 (0)8 5051 0031

United Kingdom: +44 (0) 207 107 06 13

United States: +1 (1) 631 570 56 13

Other international numbers available HERE

Webcast

Participants’ Link: https://media.choruscall.eu/mediaframe/webcast.html?webcastid=9tQW6rrU

 Sobi
Sobi is a specialised international biopharmaceutical company transforming the lives of people with rare and debilitating diseases. Providing reliable access to innovative medicines in the areas of haematology, immunology and specialty care, Sobi has approximately 1,600 employees across Europe, North America, the Middle East, Asia and Australia. In 2022, revenue amounted to SEK 18.8 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com, LinkedIn and YouTube.

Important notice

BofA Securities, a subsidiary of Bank of America Corporation, is acting exclusively for Sobi in connection with the transaction and for no one else and will not be responsible to anyone other than Sobi for providing the protections afforded to its clients or for providing advice in relation to the transaction.

Read more

MANIFEST-2 Study of Pelabresib Plus Ruxolitinib Completes Enrollment in Myelofibrosis

Posted on by

Kristi Rosa

Enrollment to the phase 3 MANIFEST-2 trial, which is examining the safety and efficacy of pelabresib plus ruxolitinib vs ruxolitinib alone in patients with JAK inhibitor–naïve myelofibrosis, has completed and topline findings are anticipated by the end of 2023.

Enrollment to the phase 3 MANIFEST-2 trial (NCT04603495), which is examining the safety and efficacy of pelabresib plus ruxolitinib (Jakafi) vs ruxolitinib alone in patients with JAK inhibitor–naïve myelofibrosis, has completed and topline findings are anticipated by the end of 2023.1

The multicenter, double-blind, placebo-controlled, trial enrolled patients with primary, post–polycythemia vera, or post–essential thrombocytopenia myelofibrosis who were at least 18 years of age, had advanced disease requiring therapy, splenomegaly by computed tomography or magnetic resonance imaging, were symptomatic, and had a prognostic risk-factor score of intermediate-1 or higher per the Dynamic International Prognostic Scoring System (DIPSS).2,3

After a screening period that lasted for up to 28 days, participants were randomly assigned 1:1 to receive ruxolitinib plus oral pelabresib or matched placebo daily for 14 consecutive days, followed by 7 days off treatment.1 Pelabresib had a starting dose of 125 mg daily, with additional dose increases allowed in accordance with trial protocol. Ruxolitinib was given in twice-daily doses of 10 mg or 15 mg based on baseline platelet counts for all 21 days of each cycle; again, dose increases were allowed per protocol criteria.

Treatment was continued until progressive disease and withdrawal of treatment. Notably, those in the control arm who experience disease progression following 24 weeks of treatment are allowed to crossover to receive the pelabresib doublet.

Patients were stratified based on DIPSS risk category (intermediate-1 vs intermediate-2 vs high), platelet count (>200 x 109/L vs 100 to 200 x 109/L), and spleen volume (≥1800 cm3 vs <1800 cm3).3

The primary end point of the trial is the proportion of patients who achieve a reduction in spleen volume of at least 35% (SVR35) at week 24 vs baseline, and a key secondary end point is the proportion of patients achieving a total symptom score improvement of at least 50% (TSS50) at week 24 vs baseline.

Other secondary end points include percentage change in TSS at week 24 vs baseline, improvement in bone marrow fibrosis by at least 1 grade at week 24 compared with baseline, SVR35 and TSS50 response at week 48 vs baseline, red blood cell (RBC) transfusion rate over the first 24 weeks of treatment, and conversion from RBC transfusion dependence to independence. Other end points include category change of Patient Global Impression of Change at week 24 vs baseline, progression-free survival, overall survival, percentage of patients with transformation to acute myeloid leukemia, toxicities, and pharmacokinetics.

“Now that MANIFEST-2 has completed enrollment earlier than anticipated, we look forward to the coming insights into the therapeutic potential of pelabresib in combination with ruxolitinib for JAK inhibitor–naïve patients with myelofibrosis,” Tim Demuth, MD, PhD, chief research and development officer at MorphoSys AG, stated in a press release. “MANIFEST-2 is the latest milestone in our efforts to improve outcomes for [patients with] blood cancer and is a testament to our continued commitment to the myelofibrosis community.”

The launch of the trial was supposed by findings from the phase 2 MANIFEST trial (NCT02158858).4 Data from the latest analysis of the trial, which had a data cutoff date of July 29, 2022, showed that 68% of JAK inhibitor–naïve patients with myelofibrosis who received pelabresib plus ruxolitinib (n = 84) achieved SVR35 at 24 weeks; at week 48, this rate was 61%, and at week 60, this rate was 54%.

Moreover, of 82 evaluable patients, 56% achieved TSS50 at week 24, indicative of a reduction in symptom burden with the combination. At week 48, 44% achieved TSS50; this rate was 43% at week 60.

Findings from an exploratory analysis of the trial showed that 27% of 63 evaluable patients experienced an improvement of at least 1 grade by week 24. This improvement was maintained at week 48 for 59% of these patients.

In terms of safety, 55% of patients experienced thrombocytopenia and 43% had anemia; these effects were grade 3 or higher in 18% and 34% of patients, respectively. Other common any-grade treatment-emergent toxicities included diarrhea (43%), respiratory tract infection (41%), asthenic conditions (38%), musculoskeletal pain (32%), constipation (30%), nausea (29%), dizziness (27%), and abdominal pain (26%).

“I think the data are exciting because they continue to demonstrate over a number of patients, over a number of centers, the benefit of combining these 2 therapies,” John Mascarenhas, MD, director of the Center of Excellence for Blood Cancers and Myeloid Disorders at Mount Sinai in New York, New York, said in a past interview with OncLive®. “We’ve done analysis that showed whether you separate patients by their prognostic score, by their molecular profile, etc, the benefit seems to be across these patients’ subgroups. It really provides additional confidence in moving this therapy into the phase 3 setting.”

References

  1. MorphoSys completes enrollment of phase 3 MANIFEST-2 study of pelabresib in myelofibrosis with topline results expected by end of 2023. News release. MorphoSys AG. April 4, 2023. Accessed May 8, 2023. https://www.morphosys.com/en/news/morphosys-completes-enrollment-phase-3-manifest-2-study-pelabresib-myelofibrosis-topline
  2. Phase 3 study of pelabresib (CPI-0610) in myelofibrosis (MF) (MANIFEST-2) (MANIFEST-2). ClinicalTrials.gov. Updated April 6, 2023. Accessed May 8, 2023. https://clinicaltrials.gov/ct2/show/NCT04603495
  3. Harrison CN, Gupta VK, Gerds AT, et al. Phase III MANIFEST-2: pelabresib + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor treatment-naïve myelofibrosis. Future Oncol. 2022;18(27):2987-2997. doi:10.2217/fon-2022-0484
  4. MorphoSys presents new longer-term phase 2 results on pelabresib in myelofibrosis, including potential disease-modifying activity, at ASH 2022. News release. MorphoSys AG. November 12, 2022. Accessed May 8, 2023. https://www.morphosys.com/en/news/morphosys-presents-new-longer-term-phase-2-results-pelabresib-myelofibrosis-including

Read more

‘Knowledge Is Exponential’ in the Rare Blood Cancer Space

Posted on by
Published on: 
Brielle Benyon

The treatment landscape for myeloproliferative neoplasms (MPNs) is ever-changing. “It’s hard to keep up, but it’s exciting,” said Dr. Steven Applebaum, a hematologist oncologist at UCLA Health in Pasadena, California.

In an interview with CURE®, Applebaum, who was recognized at 10th Annual MPN Heroes® event in December, explained that discoveries in other diseases could pave the way for a better understanding of MPNs, a rare group of blood cancers including polycythemia vera, essential thrombocythemia and myelofibrosis.

“Knowledge is somewhat exponential,” he said. “You make one discovery, which seems big, and then that kind of leads to not one more, but five more.”

Of note, Applebaum said that researchers and clinicians continue to learn more about genetic mutations and targeted therapies that will help personalize MPN therapies and make them more effective — helping patients with the disease to live longer and with a better quality of life.

Transcription

Looking at a lot of other diseases, I mean, knowledge is somewhat exponential. You make one discovery, which seems big, and then that kind of leads to not one more, but five more. The guys doing research in the lab, I expect us to learn a lot more different mutations, you know, targeted therapy. So I think we’re all really excited just looking at a lot of other diseases as a model, that there’s going to be increasing numbers of treatments that again, are going to help people live longer, but also improve their quality of life.

So the thing about being an oncologist is that (when) you’ve finished your training, you realize you don’t know anything; everything’s in evolution. So, the things I knew back then are really so cursory relative what we know now, so it’s part of what motivates us to keep going as you know that the changes in the discoveries and new treatments are going to be coming almost daily. I mean, it’s hard to keep up but it’s exciting.

Read more

Blood cancer trial finds ruxolitinib better than current treatments

Posted on by

Results from a new trial sponsored by the Cancer Research UK Clinical Trials Unit at University of Birmingham have found that ruxolitinib is better for treating patients with polycythaemia vera (PV) than the existing treatments.

PV is an incurable blood cancer and part of some conditions that affect the blood called myeloproliferative neoplasms (MPNs).

During the Phase II MAJIC-PV randomised trial, researchers studied ruxolitinib in patients who do not respond well to first line treatment.

Altogether, 180 PV patients were included in the trial, which saw the participation of various hospitals under the co-ordination of the Cancer Research UK Clinical Trials Unit.

The researchers compared the ruxolitinib drug and existing therapies.

Ruxolitinib has been designed to target JAK2 and already approved for use in PV. However, the drug is not available in the UK.

Data from the trial showed that ruxolitinib led to better disease control with normal blood counts and a minimised spleen size.

It was also found that both controlling the blood count and minimising mutated JAK2 by 50% led to fewer disease related events.

Furthermore, patients with reduced JAK2 mutation survived longer and had lower disease progression risk.

University of Birmingham Cancer Research UK Clinical Trials Unit director Pamela Kearns said: “Working on new treatments for incurable cancers is just the kind of thing that the Birmingham Cancer Research UK Clinical Trials Unit is about.

“I am really pleased that this important clinical trial has found that ruxolitinib has long-term clinical benefit for the ongoing treatment of patients with PV, and that further trials will be able to identify whether the drug can be used as an effective first line treatment.”

Read more

Learn About Rare Cancer Because ‘Uncertainty Creates Anxiety,’ Expert Says

Posted on by
Published on: 
Brielle Benyon

After a patient is diagnosed with a rare disease such as a myeloproliferative neoplasm, learning about their condition and seeking expert clinicians can help put their mind at ease.

When it comes to rare diseases such as myeloproliferative neoplasms (MPNs), gaining an understanding of the disease and seeking a specialist for treatment can help patients feel more at ease with their diagnosis, explained Dr. Raajit Rampal, an associate attending physician at Memorial Sloan Kettering Cancer Center in New York City.

MPNs are a group of rare blood cancers that many people have not heard of at the time of their diagnosis, according to Rampal, who was recognized at CURE®’s 10th Annual MPN Heroes® program in December. However, learning more about the disease and its treatment can help ease patients’ minds, as “uncertainty creates anxiety,” according to Rampal.

When it comes to developing new treatments and sparking new scientific discoveries in the MPN space, specialized doctors and researchers are essential, Rampal said.

“Sometimes (a patient will say), ‘You know, this disease is a one-in-a-million diagnosis.’ And I’ll say, ‘Yes, but you are the 10th or 11th person who I’m going to see today with it.’ That helps to further this type of research,” Rampal said in an interview with CURE.

Transcription

Well, (there are) a couple of things, a couple of challenges.

No. 1 is education. You know, when patients get diagnosed … this is a rare disease, as I often say to the patients, “This is not something your neighbor has, you’re not going to have a chat with them about that in all likelihood.” And oftentimes, what is lacking when we meet somebody who’s newly diagnosed is them having an education about this disease, they, in most cases, have never heard of this. And the doctors who see them or their primary care doctors, they’ve read about it, they don’t have seen many of these cases.

So part of our job is to educate them thoroughly. This is what you have, this is what it’s about, these are the things we can do about it. That’s partly just for the sake of education of patients, but partly because, to some extent, it relieves anxiety, right? Uncertainty creates anxiety. I’m a firm believer in that. And so, giving any type of education that will alleviate that or give somebody a better understanding will help with anxiety.

Now, on the other side of things, it’s a rare disease, and how do you bring ideas forward? You’re dealing with small numbers of patients, right? I think if you have good ideas, they are translatable. But it doesn’t stop there. Because you’re right, you can have a fantastic scientific idea. How are you going to get patients on to the study? Part of it is building a cohort and having a specialization. Doctors and researchers who are specialized in these diseases, this is most of what they see. Sometimes … (a patient will) say, “Well, you know, this disease is a one in a million diagnosis.” And I’ll say “Yes, but you are the 10th or 11th person who I’m going to see today with it.”

That helps to further this type of research. It’s not everyone (who is) going to qualify for every trial. But if you don’t have the numbers, you can’t do the research. And so making sure that, you know, us, we, as specialists, have a focus in these diseases makes a difference and that allows us to bring concepts forward for clinical trials because then we have the patients who are going to be eligible.

Read more

PharmaEssentia Initiates Phase 3b Trial of Ropeginterferon alfa-2b-njft Investigatng New Dosing Regimen for Patients With Polycythemia Vera (PV)

Posted on by

Published: May 03, 2023

Single-arm trial will evaluate an accelerated dosing schedule

BURLINGTON, Mass.–(BUSINESS WIRE)– PharmaEssentia USA Corporation, a subsidiary of PharmaEssentia Corporation (TPEx:6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced that the first patients are now being dosed in ECLIPSE PV, a Phase 3b clinical study evaluating an accelerated dosing schedule for ropeginterferon alfa-2b-njft using a prefilled syringe for the treatment of adults with polycythemia vera (PV).

Ropeginterferon alfa-2b-njft (marketed as BESREMi®) was approved by the U.S. Food and Drug Administration in November 2021 as a treatment for adults with PV.1 PV is a rare, chronic and life-threatening blood cancer caused by a mutation in hematopoietic stem cells in the bone marrow, resulting in the overproduction of red blood cells, white blood cells and platelets. Individuals with PV are at risk for serious health problems, including blood clots, stroke and heart attack.2,3 Without proper management, this debilitating cancer can progress into myelofibrosis and other malignancies, including acute myeloid leukemia.4

“This therapy represents an important addition to the treatment arsenal for PV in the U.S., and clinical data supports its use across a broad range of patients regardless of their treatment history,” said John Mascarenhas, M.D., professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai in New York. “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.”

The study will evaluate an accelerated dosing schedule for ropeginterferon alfa-2b-njft compared to the current labeled dosing. The primary endpoint is the proportion of patients achieving a CHR, defined as hematocrit <45% for at least 3 months since last phlebotomy, platelets ≤ 400 x 109/L, leukocytes ≤10 x 109/L, at 24 weeks of treatment. Approximately 100 adults with PV in the U.S. and Canada will be randomized to receive either the accelerated dosing (i.e., starting dose of 250 mcg, then 350 mcg at week 2, with a target optimal dose of 500 mcg at week 4, and then dosing will remain fixed at the highest tolerated dose for the remainder of the treatment period) or patients will receive the current labeled dosing (50 or 100 mcg starting dose with 50 mcg titration every 2 weeks). There is a 48-week study period followed by a 28-day safety follow-up. Those who respond to treatment will be eligible to participate in a long-term extension phase of the study.

“Our goal with this study is to deliver evidence on the potentially enhanced benefits of treating patients with BESREMi 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,” said Raymond Urbanski, M.D., Ph.D., U.S. Head of Clinical Development and Medical Affairs. “We believe this study will deliver further insight into the potential of BESREMi to meet the needs of PV patients.”

More information on the study including eligibility criteria can be found by visiting www.eclipsepv.com or www.clinicaltrials.gov and searching for the trial identifier NCT05481151. Topline data from the trial are expected by 2024.

Read more