PharmaEssentia’s BESREMi® (ropeginterferon alfa-2b-njft) Now Available for the Treatment of People with Polycythemia Vera in the United States

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PHARMAESSENTIA’S BESREMi® (ROPEGINTERFERON ALFA-2B-NJFT) NOW AVAILABLE FOR THE TREATMENT OF PEOPLE WITH POLYCYTHEMIA VERA IN THE UNITED STATES

BESREMi® is the only therapy indicated for adults with PV regardless of treatment history

PharmaEssentia introduces holistic services program to support prescribed patients

December 6, 2021, Burlington, MA – 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 BESREMi® (ropeginterferon alfa-2b-njft) is now commercially available in the U.S. to eligible patients with polycythemia vera (PV). BESREMi was approved by the FDA in November as the only interferon for adults with polycythemia vera. BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders.

“Today marks the beginning of a new chapter in the treatment of PV. Our team is delivering on our goal to bring an innovative solution that may help more people manage not only the symptoms of PV, but target the disease itself to gain durable control with potential to reduce progression over time,” said Meredith Manning, U.S. General Manager. “We look forward to working closely with U.S. providers to raise awareness of this therapy and help advance treatment goals.”

PharmaEssentia SOURCE Now Available to Support People with PV in the U.S.

With the commercial availability of BESREMi, PharmaEssentia is also launching a comprehensive patient support program, which can be found at www.pharmaessentiaSOURCE.com.

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U.S. FDA Approves BESREMi® (ropeginterferon alfa-ab-njft) as the Only Interferon for Adults With Polycythemia Vera

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U.S. FDA APPROVES BESREMi® (ROPEGINTERFERON ALFA-2B-NJFT) AS THE ONLY INTERFERON FOR ADULTS WITH POLYCYTHEMIA VERA

With deep, durable control demonstrated by over 7.5 years of clinical data, BESREMi® can be used at any point in the PV journey to support treatment goals

Milestone represents PharmaEssentia’s first approved indication in the United States

November 12, 2021, Burlington, MA – 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 U.S. Food and Drug Administration (FDA) has approved BESREMi® (ropeginterferon alfa-2b-njft) for the treatment of adults with polycythemia vera (PV).

BESREMi is an innovative monopegylated, long-acting interferon, which exhibits its cellular effects in polycythemia vera in the bone marrow. BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic, and infections disorders. PharmaEssentia is preparing to make BESREMi available in the coming weeks in the U.S.

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CTI BioPharma Announces Extension of FDA Review Period for Pacritinib in MF with Severe Thrombocytopenia

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SEATTLE, Nov. 30, 2021 /PRNewswire/ — CTI BioPharma Corp. (Nasdaq: CTIC) today announced the U.S. Food and Drug Administration (FDA) has extended the review period for the New Drug Application (NDA) for pacritinib for the treatment of adult patients with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) with a baseline platelet count of <50 × 109/L. The Prescription Drug User Fee Act (PDUFA) action date has been extended by three months to February 28, 2022.

In the second quarter of 2021, the FDA granted priority review for CTI’s NDA for patients with myelofibrosis with a PDUFA date of November 30, 2021. In the course of product labeling discussions, the FDA requested additional clinical data, which was submitted to the agency on November 24, 2021. Earlier today, the FDA informed the Company that it considers the data submission to constitute a “major amendment” to the NDA and therefore the PDUFA date has been extended by three months to provide additional time for a full review of the submission. At the current time, CTI is not aware of any major deficiencies in the application.

“CTI is continuing to engage collaboratively and constructively with the FDA during review of our NDA,” said Adam R. Craig, M.D., Ph.D., President and Chief Executive Officer of CTI Biopharma. “We are committed to providing patients suffering from cytopenic myelofibrosis with a new treatment option as soon as possible and are confident in pacritinib’s potential to establish a new standard of care.”

Pacritinib is a novel oral kinase inhibitor with specificity for JAK2, IRAK1 and CSF1R, without inhibiting JAK1. The NDA was accepted based on the data from the Phase 3 PERSIST-2 and PERSIST-1 and the Phase 2 PAC203 clinical trials, with a focus on the severely thrombocytopenic (platelet counts less than 50 x 109/L) patients enrolled in these studies who received pacritinib 200 mg twice a day, including both frontline treatment-naive patients and patients with prior exposure to JAK2 inhibitors. In the PERSIST-2 study, in patients with severe thrombocytopenia who were treated with pacritinib 200 mg twice a day, 29% of patients had a reduction in spleen volume of at least 35%, compared to 3% of patients receiving the best available therapy, which included ruxolitinib; 23% of patients had a reduction in total symptom scores of at least 50%, compared to 13% of patients receiving the best available therapy. In the same population of patients treated with pacritinib, adverse events were generally low grade, manageable with supportive care, and rarely led to discontinuation. Platelet counts and hemoglobin levels were also stabilized.

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Patient Story: Living with MF at 82 years old

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In 1992, I was a Technical Service Representative for a major chemical company, working with clinical laboratories, when I learned through my yearly medical checkup that my platelet count was significantly elevated.  A CBC confirmed what I suspected, essential thrombocythemia (ET). “Enjoying” the first of many bone marrow biopsies proved the diagnosis to be correct.  I met with a pathologist friend and he explained the prognosis.  Except for the elevated platelets I had no other symptoms.

Fast forward to 2004.  I’m having bloodwork checked by a hematologist prior to minor surgery.  I still had no physical symptoms of a myeloproliferative disease.  He came back into the waiting room and announced, “You have morphed into myelofibrosis.”   I didn’t want to believe it, but I knew as a certified medical technologist, MT(ASCP), that the cells don’t lie!  Years of nervous waiting followed, until in 2009 I began to experience terrible pruritis and increasing fatigue.  It was time to move to the next step.

I checked with Mayo Clinic in Scottsdale, Dr. Reuben Mesa, and with M.D. Anderson in Houston, Dr. Srdan Verstovsek.  Sure enough, the myelofibrosis was progressing and I was positive for the JAK-2 mutation.  “Dr. V” told me that a new Phase III study was to start, and that an oncologist/hematologist in San Antonio was enrolling in the study.  That was good news.  San Antonio was much closer to home!

I found my hero, Dr. Roger Lyons, now retired.   After more bloodwork, more bone marrow biopsies, he thought I was a good candidate for the Comfort I study, the first Phase III ruxolitinib study.  It was of course a doubleblind study, but by the third week of the study I knew that I had not drawn a placebo!  The itching began to cease and I felt normal. I stayed in the study through completion, and continued on what came to be called Jakafi for quite a while after.  It was a miracle!  The first drug successfully developed to treat myelofibrosis!

Then there was a problem.  In 2018, I began to develop growths on my nose.  No one suspected it had anything to do with Jakafi. When every dermatologist had exhausted the list of probable diagnoses, Dr. Lyons gave permission to discontinue the Jakafi to see what would happen.  Again, as when I started ruxolitinib, I knew very quickly that Jakafi was the culprit.  Not good news, but the positive effects of the Jakafi stayed with me for over two years.  Luck is really on my side.

Pruritis began anew in 2020, my white blood count had begun to increase, and Dr. Lyons had retired, but fortune smiled again.  Dr. Mesa, who I’d seen years ago at Mayo Clinic Scottsdale, had come to the University of Texas Health Science Center San Antonio as the head of a new partnership with M.D. Anderson Cancer Center.  As my new doctor he suggested we try Jakafi again and adjust the dose as required.  Now I take 20 mg Jakafi daily.  I’m feeling well, considering my 82 years.

 

3-Year Global MPN Interferon Initiative Report Released by MPN Research Foundation

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Chicago, IL, November 1, 2021 (Newswire.com) – In realworld usage and in clinical trials, interferon (IFN) in a variety of forms has shown high rates of hematologic and molecular responses in many patients with rare blood cancers known as myeloproliferative neoplasms (MPNs). Other patients have no significant response, and some develop drug resistance to recombinant interferon over time.

A report summarizing a three-year Interferon Initiative, released today by the MPN Research Foundation, sheds light on the reasons for these varying responses, and may have impactful applications not only for MPNs − including polycythemia vera, essential thrombocythemia and myelofibrosis − but also for other blood cancers and solid tumors.

“The initiative brought together multi-institutional investigations by key researchers from across the US, Europe and Australia to uncover a deeper understanding of the mechanisms by which interferon works for patients with an MPN,” said Barbara Van Husen, MPNRF board chair.

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Review of the Prognostic Role of Cytogenetics in MPNs

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A literature review focused on the prognostic role of cytogenetics in Philadelphia (Ph)-negative myeloproliferative neoplasms (MPN) was recently published in Medicina.

In the article, the authors concentrated on the most prevalent Ph-negative MPN classifications: polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis.

Cytogenetics has a well-established prognostic role in acute leukemias and in myelodysplastic syndromes, where it drives clinical decisions, and the cytogenetics analysis in Ph-negative MPNs can similarly offer useful information on prognosis.

Although the natural histories of Ph-negative MPNs can sometimes last decades, the authors point out that over that time, altered DNA methylation, which is associated with age and mutations, can also cause DNA breakage that can lead to deletions and duplications. Along with acquired point mutations and telomere shortening, these chromosomal alterations are also prognostically important for leukemic transformation.

The conventional method for cytogenetics is G-banding of metaphase nuclei from a cell culture to obtain a karyotype. Additional techniques include fluorescence in situ hybridization with labeled DNA probes, and hybridization with protein nucleic acid probes.

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Pharmaxis Cleared To Progress To Phase 2 Bone Marrow Cancer Trial

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PXS-5505 shows good tolerability and >90% inhibition of target enzymes LOX and LOXL2 in myelofibrosis phase 1c dose escalation study
SYDNEY, Oct. 5, 2021 /PRNewswire/ — Clinical stage drug development company Pharmaxis Ltd (ASX: PXS) today announced further positive results of data analysis from a phase 1c clinical trial (MF-101) studying its drug PXS-5505 in patients with the bone marrow cancer myelofibrosis for 28 days at three dosage levels.

Assessment with Pharmaxis’ proprietary assays of the highest dose has shown inhibition of the target enzymes, LOX and LOXL2, at greater than 90% over a 24-hour period at day 7 and day 28. The trial safety committee has reviewed the results and having identified no safety signals, has cleared the study to progress to the phase 2 dose expansion phase where 24 patients will be treated at the highest dose twice a day for 6 months.

Pharmaxis CEO Gary Phillips said, “We are very pleased to have completed the dose escalation phase of this study with such clear and positive findings. We will now immediately progress to the phase 2 dose expansion study where we aim to show PXS-5505 is safe to be taken longer term with the disease modifying effects that we have seen in the pre-clinical models. The trial infrastructure and funding is in place and we are on track to complete the study by the end of 2022.”

Independent, peer-reviewed research has demonstrated the upregulation of several lysyl oxidase family members in myelofibrosis. The level of inhibition of LOX achieved in the current study at all three doses significantly exceeds levels that caused disease modifying effects with PXS-5505 in pre-clinical models of myelofibrosis with improvements in blood cell count, diminished spleen size and reduced bone marrow fibrosis. LOXL2 was inhibited to a similar degree and based on pre-clinical work such high inhibition is likely replicated for other LOX family members (LOXL1, 3 and 4). [1] Study data can be viewed in the full announcement.

 

Management of Low-risk ET and PV Has Room for Improvement

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According to a study in the the AJMC

Despite excellent prognoses in low-risk patients with essential thrombocytopenia (ET) and polycythemia vera (PV), knowledge gaps remain and novel, more tolerable therapies require reevaluation of treatment algorithms.

Treatment of essential thrombocythemia (ET) and polycythemia vera (PV), the most common myeloproliferative neoplasms (MPNs), is based on a patient’s risk of thrombosis. However, there is controversy around the management of low-risk patients, who have distinct disease management issues from high-risk patients. A recent review aimed to provide guidance on common clinical scenarios in low-risk patients with ET and PV.

ET and PV are the most common MPNs, which are clonal stem cell neoplasms characterized by proliferation of mature myeloid lineages. The risk of arterial and venous thrombosis, which occurs in 20% to 30% of patients with ET or PV, is the most notable cause of morbidity and mortality in these diseases. Symptom management is the main goal in MPNs, and there are no treatments that alter the disease course as of yet. Even so, the prognosis for patients with low-risk ET and PV is typically measured in decades.

Risk categories for ET and PV based on the International Prognostic Score of Thrombosis for ET (R-UPSET) are as follows:

  • Very low-risk (60 years or younger, no history of thrombosis, no JAK2 V617F mutation)
  • Low-risk (60 years or younger, no history of thrombosis, presence of JAK2 V617F mutation)
  • Intermediate-risk (older than 60 years, no history of thrombosis, no JAK2 V617F mutation)
  • High-risk (older than 60 years, presence of JAK2 V617F mutation, or any history of thrombosis)

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Tipifarnib May Be Effective and Safe in Select Patients MPNs and other Diseases

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A phase 2 study suggests that tipifarnib may be more beneficial for patients with CMML, MDS, or MPNs and RAS pathway mutations than the general population of patients with these disease. 

Tipifarnib (Zarnestra) demonstrated modest efficacy benefit in patients with chronic myelomonocytic leukemia (CMML) and other myelodysplastic (MDS)/myeloproliferative neoplasms (MPNs) and was reasonably well-tolerated, according to results from a phase 2 study (NCT02807272). As a potent and highly selective farnesyl transferase inhibitor, tipifarnib therapy can be administered to work against the RAS pathway mutation that occurs in about 30% of patients with CMML and other MDS and MPNs. These mutations include NRAS, KRAS, CBL, and PTPN11. Earlier results of tipifarnib treatment showed that the agent is especially efficacious in patients with RAS wild-type CMML and in the MDS/MPN population, having high CXCR4/CXCR2 may be predictive of tipifarnib’s activity.

A total of 44 patients were included in the study and treated with tipifarnib 400 mg orally twice daily on days 1–21 of 28-day cycles. The primary end point was objective response rate (ORR) assessed per the MDS/MPN International Working Group (IWG) criteria in CMML patients with KRAS-positive or NRAS wild-type disease, and in the MDS/MPN population with high and low CXCR4/CXCR2. Secondary end points explored in the study include the adverse event profile of tipifarnib, progression-free survival (PFS) at 1 year, overall survival (OS) at 1 year, and duration of response (DOR).

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A Patient Story: A Physician Shares his MPN Diagnosis

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By Dr. Howard S.
The biggest burden I experience with my diagnosis of secondary (post PV) myelofibrosis, 21 months ago, is anxiety for my future. I am a family physician, so I knew what it meant when I no longer needed to phlebotomize after a
20-year run with polycythemia vera. For the last 10 years I injected Pegasys weekly at the top dose without any side effects and excellent control of my platelet and white blood cell count. I still required phlebotomies four times a year, but I was always saying that I am grateful to still be “proliferating!” Unlike many who struggle with myelofibrosis, I am physically asymptomatic, if you consider an hour of strenuous exercise every day (swim a mile, run 5 miles or bike 26 miles) as asymptomatic. I experience no itching and I continue to work full-time. But the question is always, “when will the other shoe drop?”

My counts are stable, no anemia, no thrombocytopenia (low platelets) and I am a “rare bird” with a diagnosis of chronic lymphocytic leukemia, also stable requiring no therapy at this time.  I did have one significant physical finding and that is an enlarged spleen known as splenomegaly. I can feel it and yet it does not interfere with my appetite or activities. I say “did” because after many months of visiting numerous East Coast MPN specialists, I decided to begin a Jak2 inhibitor at a moderate dose of 10 mg twice daily. Almost immediately my spleen decreased in size and again I am fortunate to not experience any untoward side effects. I am, of course, aware of the literature that suggests that Jak2 inhibitors may predispose to an increased number of unfavorable mutational changes but my MPN specialist does not support that viewpoint.

I have also been advised that someday in this Jak2 inhibitor may lose its beneficial effect for me and at that time (barring new advancements) I will likely need to proceed with an allogeneic stem cell transplant. Father time is not in my favor. Transplants for those over 70 years old are risky at best and in 3 months I turn 65. Even now, the data suggest a 20 percent mortality in the first year, that means one ini five people die. So pulling the trigger on a transplant is a monumental decision. Oh well…

For now, I feel well and try really hard to believe that my future will work out well for me. Because really, in the final analysis, what other choice do I have?