June 2, 2023

TAIPEI–(BUSINESS WIRE)–PharmaEssentia Corporation (TPEx:6446), a leading fully integrated biopharmaceutical company in Taiwan, today announced that it has entered into an exclusive license agreement with Pint-Pharma GmbH for the registration and promotion of BESREMi^® (ropeginterferon alfa-2b-njft) for the treatment of polycythemia vera (PV), a rare blood cancer, in Brazil, Argentina, Colombia, Chile, Peru, Ecuador, and Mexico.

“Expanding our geographic reach is critical to our mission to address clear gaps in therapeutic options for people with myeloproliferative neoplasms (MPNs). With its track record of successfully commercializing therapeutics for rare diseases and oncology, and its strong regional network, we’re confident that Pint-Pharma is the right partner to bring BESREMi to PV patients in Latin America,” said Ko-Chung Lin, Ph.D., Founder and Chief Executive Officer, PharmaEssentia. “This regional expansion is a logical extension of our growing leadership in the Americas, led by Meredith Manning. With strong momentum in the U.S., we know Meredith and her team will effectively champion the PharmaEssentia mission into Latin and South America.”

Under the terms of the agreement, PharmaEssentia may be eligible for certain milestone payments and royalties based on sales. Pint-Pharma will be responsible for obtaining and maintaining all marketing authorizations and for commercializing BESREMi in the region. PharmaEssentia will continue to be responsible for the supply of BESREMi. Pint-Pharma is an Austria-based pharmaceutical company with extensive experience in registering and commercializing rare disease, oncology and specialty treatments throughout Latin America. With this new partnership, Pint-Pharma further cements its position amongst the leaders in the field of haemato-oncology in Latin America.

“Our partnership with PharmaEssentia gives us the opportunity to provide another new treatment option to people living with MPNs in the region who are in need of effective therapies,” said David Munoz, Chief Executive Officer, Pint-Pharma. “We look forward to the potential to add BESREMi to our established haemato-oncology portfolio.”

About Polycythemia Vera
Polycythemia Vera (PV) is a cancer originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2.¹

About BESREMi (ropeginterferon alfa-2b-njft)
BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients.

BESREMi has orphan drug designation for treatment of polycythemia vera (PV) in the United States. The product was approved by the European Medicines Agency (EMA) in 2019, in the United States in 2021, and has also received approval in Taiwan, South Korea and most recently, Japan. The product was invented by PharmaEssentia and is manufactured in the company’s Taichung plant, which was cGMP certified by TFDA in 2017 and by EMA in January 2018. The company retains full global intellectual property rights for the product in all indications.

BESREMi was approved in the US with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders.

Please see accompanying full Prescribing Information, including Boxed Warning.

About PharmaEssentia

PharmaEssentia (TPEx: 6446), headquartered in Taipei, Taiwan, is a leading fully integrated biopharmaceutical company in Taiwan. Leveraging deep expertise and proven scientific principles, PharmaEssentia aims to deliver effective new biologics for challenging diseases in the areas of hematology and oncology, with one approved product and a diversifying pipeline. Founded in 2000 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today PharmaEssentia is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung, Taiwan.

Forward Looking Statement

This press release may contain forward-looking statements, including statements regarding the commercialization plans and expectations for commercializing BESREMi in Latin America, the registration and regulatory approval of BESREMi in the region, and the potential benefits of BESREMi. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 and similar legislation and regulations under Taiwanese law. These forward-looking statements are based on management expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include PharmaEssentia’s dependence on the commercial success of BESREMi, the ability to receive regulatory approvals for BESREMi in the region, whether BESREMi is successfully adopted by physicians and patients in the region, and the extent to which reimbursement is available for BESREMi in the region. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof.

¹ Cerquozzi S, Tefferi A. Blast Transformation and Fibrotic Progression in Polycythemia Vera and Essential Thrombocythemia: A Literature Review of Incidence and Risk Factors. Blood Cancer J. 2015;5, e366; doi:10.1038/bcj.2015.95

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Jun 1, 2023

Dr. Rudolf Widmann, Founder and Board Member of the AOP Health Group/ Copyright: Studio Koekart: Natasche Unkart & Isabella Köhle

June 1, 2023

VIENNA–(BUSINESS WIRE)–With the publication of the final results from the LOW-PV study in the New England Journal of Medicine Evidence conducted by Fondazione per la Ricerca dell’Ospedale di Bergamo (FROM) under the leadership of Professor Tiziano Barbui, AOP Health announces an important advancement reinforcing its clinical development program for ropeginterferon alpha-2b (BESREMi®) in polycythaemia vera (PV), a rare blood cancer. The academic LOW-PV study supported and funded by AOP Health and public organizations in Italy complements a series of trials performed by AOP Health over more than 10 years to achieve marketing authorization in Europe and the Middle East. With these clinical studies, including PEGINVERA, PROUD-PV, and CONTINUATION-PV, AOP Health opened a new area of treatment options for patients suffering from PV. A further study (PEN-PV) was performed to develop a pen for self-injection allowing ease of self-administration, exact dosing and minimal waste of the medical product. AOP Health’s comprehensive development program in PV is considered by many key opinion leaders as the most significant development in the field of PV treatment in the past 30 years.

This series of studies has enabled marketing authorizations to be obtained in numerous countries in addition to the AOP Health territories EU, Switzerland, Liechtenstein and Israel and allows patients to have access to BESREMi® in countries including Taiwan, Korea, the US, and Japan. Further studies are ongoing to substantiate the long-term safety and efficacy of BESREMi®. A post-approval safety study (BESREMI-PASS) with a recruitment period of about three years has just completed patient recruitment.

“The global marketing authorizations of BESREMi®, all based on AOP Health´s clinical development program conducted in Europe, are proof of the integrated drug development and commercialization expertise of AOP Health. Our success and know-how allow us to further pursue our goal of making treatment options for rare diseases available to patients worldwide” says Dr. Rudolf Widman, Founder and Board Member of the AOP Health Group.

About BESREMi®

BESREMi® is the first and currently only interferon approved for polycythaemia vera, a myeloproliferative neoplasm (MPN), indicated in the European Union as monotherapy in adults for treatment of polycythaemia vera without symptomatic enlarged spleen. Its overall safety and efficacy were demonstrated in multiple clinical studies.

BESREMi® (ropeginterferon alfa-2b) is a long-acting, mono-pegylated proline interferon (ATC L03AB15). It is administered with a pen (250 and 500 ug) for self-injection once every 2 weeks initially, or up to every 4 weeks after stabilization of blood values. BESREMi® is designed to be self-administered subcutaneously with a pre-filled pen.

For the EMA Summary of Product Characteristics please visit: BESREMi®

Link: https://www.ema.europa.eu/en/documents/product-information/besremi-epar-product-information_en.pdf

The drug substance Ropeginterferon alfa-2b was discovered by PharmaEssentia, a long-term partner of AOP Health. In 2009, AOP Health in-licensed the exclusive rights for clinical development and commercialization of ropeginterferon alfa-2b in polycythaemia vera and other MPNs such as chronic myelogenous leukemia (CML) for European, Commonwealth of Independent States (CIS), and Middle Eastern markets.

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Some symptoms of myeloproliferative neoplasms are “pretty broad,” highlighting the importance of open communication with cancer teams to manage the symptoms and improve quality of life.

By Rob Dillard

US veterans who were exposed to Agent Orange (AO) have an increased risk of myeloproliferative neoplasms (MPNs), bleeding, arterial thrombosis (AT), and venous thrombosis (VT), according to an analysis that will be presented at the 2023 American Society of Clinical Oncology Annual Meeting.

AO is a chemical herbicide that was weaponized and heavily used during the Vietnam War. The chemical is associated with the development of sarcomas and B-cell lymphomas, but, until now, less has been known about its link to MPNs, bleeding, AT, and VT.

To conduct their analysis, lead author Andrew Chua Tiu and colleagues used the VA Informatics and Computing Infrastructure database to identify 95,768 patients with MPN and any AT, VT, and bleeding events.

According to the results, there was a notable correlation between AO exposure and the development of MPNs (odds ratio, 1.61; 95% CI, 1.57-1.65; P<.0001). Specifically, the researchers observed that compared with patients with MPNs who were not exposed to AO, patients with MPNs who were exposed to AO had higher rates of AT (36.0% vs 28.2.%), higher rates of AT (28.7% vs 24.0%), and more bleeding events (41.2% vs 39.0%).

“This is the largest database evaluating MPNs, thrombosis, and bleeding in veterans exposed to AO. There is an association of increased risk of development of MPNs, increased AT, and increased bleeding with AO exposure,” the researchers concluded. They added that further studies “including JAK2 mutation, [clonal hematopoiesis of indeterminate potential], and cardiovascular risk factors will be needed to evaluate contribution to thrombosis and bleeding risk.”

Source: Tiu AC, McKinnell Z, Liu S, et al. Association of Agent Orange and myeloproliferative neoplasms, thrombosis, and bleeding among veterans. Abstract #7011. Published for the 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois.

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By Rob Dillard

Patients admitted for atrial fibrillation (AF) who have myeloproliferative neoplasms (MPNs) have an increased risk of any-cause and bleeding-related readmissions, according to a study that will be presented at the 2023 American Society of Clinical Oncology Annual Meeting.

Individuals with MPNs, essential thrombocythemia, polycythemia vera, and primary myelofibrosis face an increased risk of cardiovascular disease, including atrial thrombosis (AT). “[AF] is also associated with increased risk of AT and often coexists with MPN. However, thrombotic and bleeding outcomes in patients with MPN compared with those without have not been thoroughly investigated,” the investigators noted.

In this analysis, first author Orly Leiva and colleagues assessed 468,094 patients with AF and 1617 patients with a history of MPN in 2017 and 2018. Patients of interest were 18 years of age and older and were identified using the National Readmission Database. The study’s key end points were 30-day and 90-day any-cause, AT-related (including stroke, myocardial infarction, arterial thromboembolism), and bleeding-related readmissions.

According to the findings, patients with MPN had an increased risk of 30-day all-cause (hazard ratio [HR], 1.72; 95% CI, 1.70-1.74), AT-related (HR, 1.45; 95% CI, 1.38-1.53), and bleeding-related (HR, 2.21; 95% CI, 2.01-2.44) readmissions. Moreover, researchers found that patients with MPN had an increased risk of 90-day any-cause (HR, 1.38; 95% CI, 1.37-1.40) and bleeding-related (HR, 1.76; 95% CI, 1.65-1.88) but not AT-related (HR, 1.03; 95% CI, 0.99-1.08) readmissions.

“Among patients admitted for AF, MPN is associated with increased risk of 30-[day] and 90-[day] any-cause and bleeding readmissions and 30-[day] AT readmissions despite similar CHA₂DS₂-VASC and HAS-BLED risk scores,” the researchers concluded. They added that further studies “are needed to identify risk factors for bleeding and AT in patients with MPN and AF and improve on current risk scores, which do not include MPN status.”

Source: Leiva O, How Chi-Joan, Brunner A, Grevet J, Hobbs G. Outcomes of patients with a myeloproliferative neoplasm and atrial fibrillation. Abstract #7070. Published for the 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois.

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May 30, 2023

Targeted Oncology Staff

In the second part of a live discussion on treating patients with myelofibrosis, Jonathan Abbas, MD, led a talk on the impact of ruxolitinib for these patients and where physicians stand with the use of fedratinib.

May 25, 2o23

Caroline Seymour

Luspatercept-aamt (Reblozyl) led to a higher rate of sustained transfusion independence compared with erythropoiesis stimulating agents (ESAs) in patients with ESA-naïve, lower-risk myelodysplastic syndrome (MDS), according to data from the phase 3 COMMANDS trial (NCT03682536) presented in a press briefing prior to the 2023 ASCO Annual Meeting.^1,2

In the intention-to-treat population, 58.5% of patients who received luspatercept achieved transfusion independence for at least 12 weeks with hemoglobin increase of at least 1.5 g/dL compared with 31.2% of patients who received epoetin alfa, meeting the primary end point of the study (P < .0001).

“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in transfusion-dependent lower-risk MDS, [and this should be] considered a paradigm shift in the treatment of lower-risk MDS–associated anemia,” Guillermo Garcia-Manero, MD, lead study author and professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, said in a presentation of the data.

Anemia is one of the main symptom burdens for patients with MDS, and chronic anemia and transfusion dependence in lower-risk MDS presents challenges in the clinic, often leading to increased risk of death compared with patients who are transfusion independent. Additionally, standard treatment with ESAs is associated with modest activity, leaving an unmet need for treatment in this population.

Luspatercept is a monoclonal antibody that affects the TGF-beta pathway, leading to increased erythrocytosis. The agent is currently indicated for the treatment of patients with ring sideroblast–positive, lower-risk MDS with progression on or ineligibility for an ESA.

COMMANDS was an open-label, global, randomized trial that enrolled patients at least 18 years of age with Revised International Prognostic Scoring System very low–, low-, or intermediate-risk MDS with or without ring sideroblasts by World Health Organization 2016 criteria with less than 5% blasts in bone marrow. In addition, patients had to have required between 2 and 6 packed red blood cell units per 8 weeks for at least 8 weeks prior to randomization, endogenous serum erythropoietin less than 500 U/L, and lack of prior exposure to ESA therapy.

Patients were stratified by baseline serum erythropoietin level (≤200 U/L vs >200-500 U/L), baseline red blood cell transfusion burden (<4 U/8 weeks vs ≥4 U/8 weeks), and ring sideroblast status (positive vs negative).

The primary end point of the study was the rate of red blood cell transfusion independence for 12 weeks or more with concurrent mean hemoglobin increase of at least 1.5 g/dL.

Eligible patients were randomly assigned 1:1 to receive 1.0 mg/kg of subcutaneous luspatercept every 3 weeks titrated up to 1.75 mg/kg (n = 178) or 450 IU/kg of subcutaneous epoetin alfa every week titrated up to 1050 IU/kg (n = 178). Patients were evaluated for response at day 169 and every 24 weeks thereafter. Treatment was discontinued in the absence of clinical benefit or disease progression per International Working Group criteria. After treatment was completed, patients were followed for other malignancies, high-risk MDS or acute myeloid leukemia (AML) progression, subsequent therapy, and survival for 5 years from the first dose of study treatment of 3 years from the last dose, whichever occurred last.

The median duration of treatment was 41.6 weeks (range, 0-165) with luspatercept vs 27.0 weeks (range, 0-171) with epoetin alfa.

Additional results demonstrated higher rates of transfusion independence with luspatercept regardless of stratification criteria. Moreover, patients experienced improved rates of transfusion independence with luspatercept regardless of SF3B1 mutation status.

Notably, treatment with luspatercept led to prolonged transfusion independence regardless of ring sideroblast status. “Luspatercept provided clinical benefit regardless of patient subgroups,” Garcia-Manero added.

In all patients, the median duration of transfusion independence for at least 12 weeks was 126.6 weeks (95% CI, 108.3–not evaluable [NE]) with luspatercept vs 77.0 weeks (95% CI, 39.0-NE) with epoetin alfa (HR, 0.456; 95% CI, 0.260-0.798). In ring sideroblast–positive patients, the median durations were 120.9 weeks (95% CI, 76.4-NE) and 47.0 weeks (95% CI, 36.6-NE) with luspatercept and epoetin alfa, respectively (HR, 0.626; 95% CI, 0.361-1.085). In ring sideroblast–negative patients, the median durations were NE (95% CI, 46.0-NE) and 95.1 weeks (95% CI, 35.3-NE), respectively (HR, 0.492; 95% CI, 0.148-1.638).

Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 92.1% (n = 164) of patients in the luspatercept arm vs 85.2% (n = 150) of patients in the epoetin alfa arm.

“The toxicity profile was consistent with previous clinical experience,” Garcia-Manero stated.

Any-grade hematologic toxicities in the luspatercept and epoetin alfa arms, respectively, included anemia (9.6% vs 9.7%), thrombocytopenia (6.2% vs 1.7%), neutropenia (5.1% vs 7.4%), and leukocytopenia (1.1% vs 1.7%). Any-grade TEAEs of interest include fatigue (14.6% vs 6.8%), diarrhea (14.6% vs 11.4%), peripheral edema (12.9% vs 6.8%), asthenia (12.4% vs 14.2%), nausea (11.8% vs 7.4%), dyspnea (11.8% vs 7.4%), and thromboembolic event (4.5% vs 2.8%).

Moreover, patients in the luspatercept arm experienced fewer progressions to high-risk MDS and AML compared with patients in the epoetin alfa arm, at 2.8% (n = 5) and 2.2% (n = 4) vs 4.0% (n = 7) and 2.8% (n = 5), respectively. Thirty-two fatalities occurred in both arms.

“In patients with anemia with lower-risk MDS who depend on red blood cell transfusions, luspatercept almost doubles the number of people who achieve independence from transfusions for a period lasting 12 weeks or more, when compared with epoetin alfa, a current standard of care treatment. Luspatercept may be an effective first treatment option for anemia associated with lower-risk MDS,” Olatoyosi Odenike, MD, FASCO, a professor of medicine and director of the Leukemia Program at University of Chicago Medicine, stated in a news release.

References

1. Garcia-Manero G, Platzbecker U, Santini V, et al. Efficacy and safety results from the COMMANDS trial: A phase 3 study evaluating luspatercept vs epoetin alfa in erythropoiesis-stimulating agent (ESA)‑naive transfusion-dependent (TD) patients (pts) with lower‑risk myelodysplastic syndromes (LR-MDS). J Clin Oncol. 2023;41(suppl 16):7003. doi:10.1200/JCO.2023.41.16_suppl.7003
2. Luspatercept improves anemia and reduces reliance on blood transfusions for people with lower-risk myelodysplastic syndromes. News release. ASCO. May 25, 2023. Accessed May 25, 2023. https://old-prod.asco.org/about-asco/press-center/news-releases/luspatercept-improves-anemia-and-reduces-reliance-blood

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By Dr. Priyom Bose PhD

May 25, 2023

Myeloproliferative neoplasm (MPN) represents a group of inflammatory diseases, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPNs are linked to hematologic malignancies and are characterized by clonal outgrowth of hematopoietic cells with an acquired mutation in JAK2.

Multiple studies have shown that the Mediterranean diet positively impacts diseases associated with chronic subclinical inflammation. In addition to the Mediterranean diet, the gut microbiome also plays a crucial role in improving hematologic disorders.

A new study published to the medRxiv* preprint server assesses the feasibility of an education-focused Mediterranean diet intervention among MPN patients.

Background

Clinical manifestations of MPN include abnormal blood counts, thrombosis, and transformation to acute leukemia. One of the key characteristic features of MPN is increased plasma cytokines.

Chronic inflammation leads to abnormal blood count. Although JAK inhibitors alleviate MPN symptoms, these drugs are associated with certain risks, such as immunosuppression, skin cancer, and weight gain.

The recent National Comprehensive Cancer Network (NCCN) guidelines for MPN proposed several interventions to reduce symptom burden, irrespective of the prognosis scoring category.

Since many MPN patients do not meet the criteria for a cytoreductive agent, their symptoms are maintained without specific interventions. As a result, the quality of life of these patients is adversely affected due to the inability to limit disease progression.

Lifestyle modification, mainly through diet, can reduce inflammation. For example, a healthy diet high in anti-inflammatory agents can improve symptom burden among MPN patients. Adherence to this type of diet can decrease inflammation and significantly delay or prevent disease progression.

The Mediterranean diet is a primarily plant-based diet, which is associated with the consumption of nuts, extra virgin olive oil (EVOO), vegetables, fish, fruits, legumes, and whole grain products. Controlling inflammation through nutrition is a low-risk therapeutic approach to mitigate the burden of symptoms for MPN patients.

About the study

The primary aim of the current study was to determine the willingness of MPN patients to engage in dietary education to manage symptom burden. Participants were randomly assigned to either a standard U.S. Dietary Guidelines for Americans (USDA) group or Mediterranean diet group. Both groups received separate but equal education through written dietary resources and registered dietician counseling.

Patients were followed for adherence, feasibility, and symptom burden assessments. To explore changes in the gut microbiome and inflammatory biomarkers, biological samples were collected at four distinct time points throughout the 15-week study period.

Study findings

MPN patients found the Mediterranean diet program equally easy to follow as a program based on the U.S. Guidelines for Americans. Over 80% of participants in the Mediterranean diet group could maintain good adherence throughout the intervention period as compared to less than 50% in the USDA group. This serves as evidence that, with proper dietician counseling and written curriculum, MPN patients can feasibly adopt a Mediterranean diet.

MPN patients can adopt a Mediterranean eating pattern with dietician counseling and education. (A) Percentage of participant with MEDAS scores ≥8 at each time point with orange shaded area depicting the active intervention period (B) Participant responses to feasibility question during active intervention period (C) HEI-2015 was calculated from each 24 hour diet recall, and scores for each participant were averaged for the pre-intervention (weeks 1-2), active intervention (weeks 3-12), and post-intervention (weeks 13-15) period. Data shown represents median with interquartile range.

In MPN, an important goal is to target symptoms, as symptoms can significantly affect the patient’s’ quality of life. In the USDA group, 31% of the cohort exhibited more than a 50% reduction in the MPN-Total Symptom Score (TSS) at 15 weeks, whereas 53% of the Mediterranean diet group exhibited more than a 50% reduction in the MPN-TSS.

As compared to the USDA diet, the Mediterranean diet had a better effect on alleviating MPN symptoms. The length of the diet intervention and intensity are important factors in alleviating MPN symptoms.

Changes in symptom burden during study. (A) waterfall plots of percentage change in MPN-SAF (MPN-TSS) at each week compared to baseline (baseline defined as average MPN-TSS of weeks 1 and 2) (B) Raw change in specific symptoms at each week compared to baseline (mean±SD).

Future outlook

Both diets investigated in the current study led to a reduction in MPN symptom burden. Thus, these findings demonstrate that a 10-week intervention is sufficient to detect a change in symptoms.

In the future, a longer intervention period is required to assess whether improvements in symptoms continue. A longer intervention period would also help detect people with delayed symptom improvement.

The current analysis highlights that MPN symptoms may stem from different root causes; therefore, some symptoms change quickly compared to others. Due to the small sample size, a decrease in the inflammatory cytokines could not be detected. Therefore, future studies with a larger cohort are needed to elucidate how diets impact inflammatory cytokine levels.