Women’s History Month – Ann Mullally, MD

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Ann Mullally, MD is an Associate Professor, Medicine, Harvard Medical School, an Attending Physician, Leukemia Program, Medical Oncology, Dana-Farber Cancer Institute and an Associate Physician, Hematology, Brigham And Women’s Hospital. She is a translational cancer researcher in the field of myeloid malignancies, with a focus on myeloproliferative neoplasms (MPN).

How did you become interested in hematology versus other areas of medicine?

I became really interested in hematology during residency training at Johns Hopkins where I became fascinated by acute leukemia.I became interested in lab-based research in hematology during fellowship at Brigham/Dana-Farber and I joined the lab of Dr. Gary Gilliland, who co-discovered the JAK2V617F mutation. That set me on path studying MPN.

What have been the highlights in your career, specifically in the area of MPNs?

I am very proud of our work deciphering the mechanism by which mutations in calreticulin cause MPN. I hope this work and that of others in the field will ultimately result in curative therapies for patients with CALR-mutant MPN.

I also feel privileged to have a MPN clinic and witness firsthand the challenges faced by our patients and the deficiencies of our treatments, which both provide huge motivation for researchers like myself to do better.

As a female in this area of medicine, what advice would you give women grappling with career choices in hematology and medical research?

Still in 2022, women face many challenges in academic medicine including the gender pay gap, under-representation in senior faculty and leadership positions and gender inequity in recruitment, promotion and retention to name but a few.

In order to overcome these challenges medicine needs to be remodeled and this is an active and ongoing process. My advice would be that the best way to have your voice heard is to be in the room, so come join us!

Insights on the Post Polycythemia Vera Myelofibrosis (PPV-MF) Market to 2027

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03-14-2022 11:27 AM CET

Press release from Orion Market Research

 

The global post polycythemia vera myelofibrosis (PPV-MF) market is anticipated to grow at a significant CAGR during the forecast period (2021-2027). Post-polycythemia vera myelofibrosis is a form of the myeloproliferative neoplasm and is also called chronic idiopathic myelofibrosis. It is a rare chronic blood cancer. People with myelofibrosis (MF) have a defect in their bone marrow that results in an abnormal production of blood cells which causes scar tissue to form. The major factor driving the growth of the market is the increasing prevalence of polycythemia vera (PV) across the globe.

According to the Leukemia & Lymphoma Society, PV is more prevalent among Jews of Eastern European descent than other Europeans or Asians. However, the incidence of PV is about 2.8 per 100,000 population of men and about 1.3 per 100,000 population of women of all races. Additionally, an estimated number of people in a population with PV is about 22 cases per 100,000 people. Furthermore, PV is mostly diagnosed at the average age of 60 to 65 years and it is uncommon in individuals younger than 30 years. Hence, the increasing prevalence of PV is driving the growth of the global post polycythemia vera myelofibrosis (PPV-MF) market.

To Request a Sample of our Report on Post Polycythemia Vera Myelofibrosis (PPV-MF) Market: https://www.omrglobal.com/request-sample/post-polycythemia-vera-myelofibrosis-ppv-mf-market

Researchers solve the structure of large signaling protein involved in emergence of blood cancers

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Researchers led by Christopher Garcia of the Ludwig Center at Stanford University have solved the long-sought structure of a large signaling protein involved in responses to infection, inflammation, the generation of immune cells, and when dysregulated by mutation-; the emergence of blood cancers known as myeloproliferative neoplasms. Published in the journal Science, the structure reveals the mechanism by which this protein, Janus kinase (JAK), transmits signals sent by immune cell growth factors called cytokines.

That structural information has direct implications for the development of new drugs for myeloproliferative neoplasms, which are currently treated with drugs often referred to as “jakinibs” that target all JAK proteins, not just the mutants that drive cancer. This broad targeting of JAK proteins causes side effects that include anemia and thrombocytopenia, a blood clotting disorder.

“Our model of JAK structure gives us an atomic blueprint for how one could make mutant-selective medicines to treat these cancers,” said Garcia. “This is the essence of basic discovery biology leading to translational insights.”

Cytokines signal through receptors found on the cell surface that thread through the cell’s outer membrane into its cytoplasm. Each receptor has attached to its cytoplasmic tail, a single JAK protein in an inactive state. Each cytokine protein binds two of these receptors, drawing their attached JAKs together.

“When the JAKs are brought close together, they activate one another,” Garcia explained. “That’s the activated complex that gets the signaling engine running.”

Each JAK phosphorylates-; or adds a phosphate molecule-; to a specific spot on its partner. So activated, the JAKs then phosphorylate the cytokine receptor to which they’re attached, drawing a protein known as STAT to the complex. It is this complex that transmits the cytokine’s growth-promoting signal.

The structure solved by Garcia’s lab, which has pursued this prize for more than two decades, is of the JAKs in their juxtaposed and activated state.

“Small pieces of the JAK structure had been published over the years-; a toe here, a finger there, an ear there-; but nobody had seen what the whole body looked like, so to speak,” said Garcia.

The full structure shows that when drawn together by the cytokine, the JAKs meet at a roughly flattened region in their middle. The change induced by the oncogenic JAK mutation-; swapping the smaller amino acid valine for the much larger phenylalanine-; falls in the middle of this region. The mutation alters the flat interface between the JAKs, creating a sort of ball and socket connection between the two that makes them adhere far more firmly to one another.

“When people have this mutation-; the most classical mutation in blood cancers-; the JAKs come together and start working all the time because there’s like a little dab of glue in there that’s bringing them together even when there’s no cytokine around,” Garcia said. They thus continuously transmit growth signals, driving cell proliferation.

The finding opens the door to developing small molecules that disrupt the ball-and-socket connection of the mutant JAKs. Such drugs would not affect normal JAK proteins and would, therefore, be less likely to have toxic side effects.

Garcia and his colleagues solved the structure of the mouse JAK-1 protein. The “V617F” mutation that drives myeloproliferative neoplasms is, however, found in its cousin, JAK-2. But, Garcia says, the two are sufficiently alike to share the same signaling mechanism.

Garcia’s group is now working on developing drugs to target V617F mutant JAKs and capturing the structure of the larger JAK-STAT complex and that of the complexes formed between different types of JAKs, which are also involved in cytokine signaling.

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Women’s History Month – Claire Harrison, MD

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Claire Harrison, MD, DM, FRCP, FRCPath is a Professor of Hematology at the Guy’s and St. Thomas’ NHS Foundation Trust in London, UK. Prof. Harrison became a Consultant at the Guy’s and St. Thomas’ NHS Foundation Trust in 2001, where she is now a Clinical Director. 

1. How did you become interested in hematology versus other areas of medicine?

Haematology captivated me as a student at Oxford I had the privilege of being taught by Prof Sir David Weatherall I think it was the opportunity to both bring science direct to the bedside and to look after patients with a chronic illness.

2.  What have been the highlights in your career, specifically in the area of MPNs?

Working in an area you are passionate about with a fabulous team locally and many others.. the fantastic international community of clinicians and scientists and the strong partnership with patient communities and also colleagues in biotech and pharma who are pushing the boundaries to improve the lives of our patients.

3.  As a female in this area of medicine, what advice would you give women grappling with career choices in hematology and medical research? 

It’s the same advice regardless of gender….  Find something that you are passionate about, identify a mentor or two, don’t be afraid to admit if you don’t know always ask, balancing work and family life is a challenge but feasible keep looking for solutions.

Women’s History Month – Gabriela Hobbs, MD

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Dr. Hobbs is the clinical director of the adult leukemia service at Massachusetts General Hospital. Her clinical and research interests are myeloproliferative neoplasms and chronic myeloid leukemia.

1.How did you become interested in hematology versus other areas of medicine?

I’ve been drawn to hematology my whole life. My first real awareness of this was when I read a children’s book about Louis Pasteur and his search for a vaccine for rabies asa young child. The idea that we had soldiers (aka immune cells) in our body that could be used to fight illness was simply fascinating. I remember staring at my hands and trying to see if I could catch a glimpse of one of these bad germs.

2.What have been the highlights in your career, specifically in the area of MPNs?

One huge highlight was when I was hired at MGH to develop a clinical and research program for MPN patients as MGH. Another, more recent highlight was when I had the opportunity to present results of a clinical trial I lead investigating the role of ruxolitinib before, during and after transplant for myelofibrosis. The outcomes with this approach have been excellent and I feel excited to be able to have contributed to improving outcomes for MF patients.  Lastly, I love being a mentor and helping trainees through their journey as clinicians and researchers, I recently saw one of my mentee’s get her first faculty position and it was a very rewarding experience.

3. As a female in this area of medicine, what advice would you give women grappling with career choices in hematology and medical research?

When I was in training I remember feeling intimidated by a career in hematologic malignancies and thought that maintaining work life balance would be difficult. However, I quickly realized that if I didn’t pursue a field of medicine that I was passionate, I would never be satisfied with work and honestly, there is no such thing as an easy career in medicine. What I tell my mentees is, choose something you love so that you are excited to go to work every day but don’t be afraid to set boundaries between work and life, this will ensure your career success by allowing you to stay in medicine longer and avoid burn out.

Women’s History Month-Wendy Erber, MD

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Professor Wendy Erber is Professor of Pathology and Laboratory Medicine and a diagnostic haematologist at the University of Western Australia.

1. How did you become interested in hematology versus other areas of medicine?

My interest in hematology was driven by a passion to understand the cause of blood diseases. If we understand causation, we may have a better chance of accurate diagnosis, targeted treatments and (possibly) prevention. I had the opportunity to learn from and study under the supervision of a wonderful scientist cum diagnostic hematologist at the University of Oxford. His passion for the field was infectious, and I continued on from 4 stimulating years under his guidance. His mentorship was a key component that led me down this career path. There is another answer I could give. You will find it on my TEDx talk:  https://www.youtube.com/watch?v=BcjVx8LtCqM

2.  What have been the highlights in your career, specifically in the area of MPNs?

My career highlights in the field of MPNs have included contributing to our knowledge of the importance of the JAK2 gene. My role in assessing the bone marrow pathology informed patient diagnoses and their care. JAK2 testing was then introduced as a routine and this has helped discriminate between reactive causes of thrombocytosis and MPN. This has been a paradigm shift in diagnosis that has benefited patients and their care.

3.  As a female in this area of medicine, what advice would you give women grappling with career choices in hematology and medical research?

Follow your passion. Work with the best you can. Take opportunities when they arise. And, if you do these things, you are likely to enjoy your career and be successful. You may have failures along the way: we all do! But if you don’t try, you’ll never succeed!

NCCN Clinical Practice Guidelines in Oncology Update Recommends BESREMi® (ropeginterferon alfa-2b-njft) for the Treatment of Polycythemia Vera

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Reflecting its strong clinical profile and broad label, NCCN Guidelines include BESREMi as an
option for PV regardless of treatment history, and for use in both low- and high-risk settings

March 2, 2022, Burlington, MA – PharmaEssentia USA Corporation, the U.S. 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 National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) has been updated to include BESREMi® (ropeginterferon alfa-2b-njft) as a recommended therapeutic option for the treatment of adults with polycythemia vera (PV).

The NCCN is a highly renowned and respected not-for-profit alliance of leading cancer centers in the United States. Its treatment practice guidelines are widely respected and followed by the U.S. physician community, and serve to inform and facilitate coverage decisions with payers for oncology therapies. Consistent with the broad indication for BESREMi upon its U.S. regulatory approval in November 2021, the guidelines provide consideration for use of the treatment among both high-risk and low-risk adult patients, regardless of their treatment history.

“Importantly, the NCCN Guidelines update includes mention of BESREMi in multiple settings, and in particular, as the only systemic option for low-risk patients with PV, which signals a shift toward more proactive treatment earlier in the disease journey,” said Ruben Mesa, M.D., FACP, Executive Director of the UT Health San Antonio MD Anderson Cancer Center. “Now, treating physicians can leverage these expert guidelines to gain greater familiarity with BESREMi in the real world setting and understand its broad utility for patient care in a variety of treatment settings.”

“Our goal with BESREMi has been to offer a compelling therapeutic alternative to conventional treatment options that can enable physicians to gain durable control over the disease beyond the symptoms and help more patients reach their long-term health goals,” said Raymond
Urbanski, M.D., Ph.D., U.S. Head of Clinical Development and Medical Affairs. “The NCCN Guidelines update just three months following our approval illustrates the community’s recognition of the strong potential of BESREMi in PV care.”

 

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CTI BioPharma Announces FDA Accelerated Approval of VONJO™ (pacritinib) for the Treatment of Adult Patients with Myelofibrosis and Thrombocytopenia

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– VONJO is the First Approved Therapy to Specifically Address the Needs of Adult Cytopenic Myelofibrosis Patients –
– NDA Approved Under Priority Review –
– Approval Triggers $60 Million Payment from DRI Healthcare Trust –
– CTI to Host Conference Call Tomorrow at 8:00 a.m. ET –

SEATTLE, Feb. 28, 2022 /PRNewswire/ — CTI BioPharma Corp. (Nasdaq: CTIC) today announced the U.S. Food and Drug Administration (FDA) has approved VONJO (pacritinib) 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. VONJO is a novel oral kinase inhibitor with specificity for JAK2 and IRAK1, without inhibiting JAK1. The recommended dosage of VONJO is 200 mg orally twice daily. VONJO is the first approved therapy that specifically addresses the needs of patients with cytopenic myelofibrosis.

“Today’s approval of VONJO establishes a new standard of care for myelofibrosis patients suffering from cytopenic myelofibrosis,” said John Mascarenhas, M.D., Associate Professor, Medicine, Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. “Myelofibrosis with severe thrombocytopenia, defined as blood platelet counts below 50 × 109/L, has been shown to result in poor survival outcomes coupled with debilitating symptoms. Limited treatment options have rendered this disease as an area of urgent unmet medical need. I am pleased to see that a new, efficacious and safe treatment option is now available for these patients.”

“In the U.S., there are approximately 21,000 patients with myelofibrosis, two-thirds of which have cytopenias (thrombocytopenia or anemia), commonly resulting from the toxicity of other approved therapies. Severe thrombocytopenia, defined as a blood platelet count below 50 × 109/L, occurs in one-third of the overall myelofibrosis population, and has a particularly poor prognosis. With the approval of VONJO, we are excited to now be able to offer a new therapy that is specifically approved for patients with cytopenic myelofibrosis. We are fully funded for commercial launch, following our debt and royalty transactions with DRI, and we look forward to providing VONJO, the potential best-in-class therapy for cytopenic myelofibrosis patients, to patients within 10 days,” said Adam R. Craig, M.D., Ph.D., President and Chief Executive Officer of CTI Biopharma. “I would like to thank the patients, caregivers, clinical trial staff and investigators who made the VONJO clinical trials possible. I am also thankful to the CTI team for their hard work and dedication and their focus on the needs of patients.”

The accelerated approval is based on efficacy results from the pivotal Phase 3 PERSIST-2 study of VONJO in patients with myelofibrosis (platelet counts less than or equal to 100 × 109/L). Patients were randomized 1:1:1 to receive VONJO 200 mg twice daily (BID), VONJO 400 mg once daily (QD) or best available therapy (BAT). Prior JAK2 inhibitor therapy was permitted. In this study, in the cohort of patients with baseline platelet counts below 50 × 109/L who were treated with pacritinib 200 mg BD, 29% of patients had a reduction in spleen volume of at least 35% compared to 3% of patients receiving best available therapy, which included ruxolitinib. As part of the accelerated approval, CTI is required to describe a clinical benefit in a confirmatory trial. To fulfil this post-approval requirement, CTI plans to complete the PACIFICA trial, with expected results in mid-2025.

The most common adverse reactions (≥20%) following VONJO 200 mg twice daily were diarrhea, thrombocytopenia, nausea, anemia and peripheral edema. The most frequent serious adverse reactions (≥3%) following VONJO 200 mg twice daily were anemia, thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia and squamous cell carcinoma of skin.

CTI is committed to supporting patients with myelofibrosis and removing barriers to access. As part of that commitment, CTI has established CTI Access, a patient support program that provides reimbursement and financial assistance programs for eligible patients. For more information, visit www.CTIaccess.com.

Under the terms of the previously announced debt and royalty transaction with DRI Healthcare Trust, the FDA approval of VONJO triggers the acquisition by DRI of a tiered royalty on VONJO for US$60 million. The proceeds of the transactions will be used by CTI to fund the launch of VONJO. As of December 31, 2021, CTI had cash and cash equivalents of approximately $65 million.

Conference Call and Webcast
CTI will host a conference call and webcast to discuss this announcement tomorrow, March 1, at 8:00 a.m. ET. To access the live call by phone please dial (877) 735-2860 (domestic) or (602) 563-8791 (international); the conference ID is 8860186. A live audio webcast of the event may also be accessed through the “Investors” section of CTI’s website at www.ctibiopharma.com. A replay of the webcast will be available for 30 days following the event.

About VONJO (pacritinib)
Pacritinib is an oral kinase inhibitor with activity against wild type Janus Associated Kinase 2 (JAK2), mutant JAK2V617F form and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Myelofibrosis is often associated with dysregulated JAK2 signaling. Pacritinib has higher inhibitory activity for JAK2 over other family members, JAK3 and TYK2. At clinically relevant concentrations, pacritinib does not inhibit JAK1. Pacritinib exhibits inhibitory activity against additional cellular kinases (such as CSF1R and IRAK1), the clinical relevance of which is unknown.

VONJO is indicated 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 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).


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Legislative and Policy Updates That Could Impact Your Healthcare

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– Strong support for extending telehealth flexibilities
With uncertainty around when the Biden administration will end the Public Health Emergency declaration, members of Congress and stakeholders are seeking a temporary extension of the Medicare telehealth waivers implemented during the pandemic. To that end, Senators Catherine Cortez Masto (D-NV) and Todd Young (R-IN) have introduced the Telehealth Extension and Evaluation Act (S.3593) and Representative Lloyd Doggett (D-TX) has introduced the Telehealth Extension Act (H.R. 6202) that both include an extension of the telehealth waivers for two years. In addition, more than 300 health groups sent a letter to House and Senate leadership urging a temporary extension before taking up permanent comprehensive telehealth legislation.

– FY2022 annual spending bills under negotiation
Federal government spending is operating under a continuing resolution through March 11, five months after the start of fiscal year 2022. This will allow time for negotiations on the 12 annual spending bills. A deal was recently reached on the top-line spending amount for the bills as well as the allocations for the 12 bills. Negotiations center around both funding levels and policy issues to be addressed in the bills. In addition to the annual appropriations bills, the White House is expected to ask Congress for emergency supplemental funding to address the COVID pandemic as well as prepare for future pandemics.

– President to address a joint session of Congress on March 1
The President will make his State of the Union address on March 1 to lay out his priorities for the nation. The President’s FY2023 budget request is expected to be released in late March or early April. The delay in the release of the President’s budget will likely impact Congress’ timeline for receiving input and developing the FY2023 annual spending bills.

– Congressional focus mental health and substance use
Committees in the House and Senate have been holding hearings on mental health and substance use to inform the development of legislation to be released in a spring/summer timeframe. The COVID-19 pandemic has exacerbated the need for services and highlighted the workforce challenges and disjointed systems of care. In addition, there are a wide range of Substance Abuse and Mental Health Services Administration programs that expire in September.
The Senate Finance Committee announced five areas of focus for their legislation:
  • strengthening the workforce
  • increasing integration, coordination, and access to care
  • ensuring parity between behavioral and physical health care
  • furthering the use of telehealth
  • improving access for children and young people
The Senate Health, Education, Labor, and Pensions Committee and the House Energy and Commerce Committee are also developing legislation.

– CMS maintains the previous administration’s position on co-pay accumulators in exchange plans
In January, CMS issued the proposed rule Notice of Benefit and Payment Parameters for 2023 for qualified health plans offered through federal and state Affordable Care Act insurance exchanges. CMS is proposing to strengthen plan offerings by reinstating standardized benefits plans with flat dollar co-pays for specialty medication and strong non-discrimination protections.
However, the rule does not include any reference to co-pay accumulator adjustment policies and therefore does not reverse the Trump administration’s decision to allow insurers and pharmacy benefit managers to include co-pay accumulator adjustment policies in their plans. PAN submitted comments requesting CMS reinstate the agency’s original rule requiring issuers to count all payments made by or on behalf of the beneficiary, including patient co-pay assistance, toward patients’ annual deductible and out-of-pocket limit.

– MedPAC discusses prescription drugs telehealth
The Medicare Payment Advisory Commission (MedPAC) held a meeting in January in which the commissioners reviewed the status of the Medicare Part D program in preparation for their report to Congress in March. One notable trend in Part D is that a small share of enrollees who reach the catastrophic phase drive overall spending. At future meetings, commissioners will review MedPAC’s previous recommendations to strengthen Medicare Part D.

Myelofibrosis market to see new approvals in 2022, driving market growth

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Myelofibrosis is a rare hematological malignancy with limited therapeutic options and significant unmet clinical need. Current first line therapy options are two Janus kinase (JAK) inhibitors (JAKis), Incyte’s Jakavi/Jakafi (ruxolitinib) and Impact Biomedicine’s Inrebic (fedratinib). Jakafi has dominated the myelofibrosis market since its launch in 2011 and has seen lucrative financial returns, achieving blockbuster status. However, Jakafi is not a curative agent. Since patients often discontinue the treatment and experience exacerbated anemia, clinicians prescribe additional lines of therapy. Several pipeline JAKis have entered Phase III trials, seeking to expand the lines of therapy by targeting Jakafi-refractory patients, capitalizing on a currently underserved patient population.

Notably, topline data have recently been released from the randomized, double-blind, active control Phase III MOMENTUM study comparing the selective JAK1, JAK2 and ACVR1 inhibitor, Sierra Oncology’s momelotinib, versus the anti-anemia molecule danazol. In Jakafi-refractory patients, momelotinib achieved all prespecified primary and secondary endpoints. A total of 25% (n=130) of patients experienced a total symptom score (TSS) reduction of ≥50% on momelotinib, demonstrating clear superiority to danazol (TSS reduction ≥50% in 9% of patients). Momelotinib was also superior in splenic response rate (SRR) compared to danazol (23% versus 3%) and demonstrated promising safety data with 54% of patients experiencing grade 3 or higher toxicities, compared to 65% on danazol.

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