Science & Medicine

January, 2020


Best wishes  this Holiday Season

May it be an island of peace, hope and good will for you and for all.       

(Sincere thanks to all who support us with work, contributions, and just being there.)

Although most of us have never met one another we regularly come together as a community sharing not only our stories and  MPN struggles but our concern and support for one another.

Zhenya Senyak

 At the breaking dawn of 2020 we are at a true medical cross-roads, compounding the difficulty of selecting an optimal therapeutic path:  Watch & Wait, alternative approaches, drugs, stem cell transplant, clinical trial.

And on the horizon – our holy grail:  immunotherapy, gene editing, cure.

The Genomic Revolution – offering the possibility of correction rather than inhibition — has already reached the shores of hematology. Closely related blood diseases are being treated right now. (See, TSR, below.)  Our time is coming.  Can we wait? Can we sort out Big Pharma’s claims?

The drug companies and their agents outgun us. Consider Incyte’s direct to patient TV ads on Jakafi for PV.  Or the strange saga of Fedratinib (by any of its several names), once dead in the water, now an FDA approved MF drug folded into a Bristol-Myers Squibb acquisition of Celgene for a reported $74 billions dollars.  (What’s in your wallet?)

I have been part of this community for almost 25 years.  My work in science reporting and patient advocacy has brought me in contact with hundreds of MPN patients, and many specialists, transplanters and  scientists. And I’m worried.  Things have changed. Sometimes for the better, most often for the worse.

My concern for my friends, fellow patients, caregivers, physicians, and workers in MPN patient support lead me to offer this year-end report, a personal perspective on a few key events that have transformed the MPN community this past decade. And suggest what may lie ahead.



 The 21st  Annual  Meeting & Exposition of the American Society of Hematology in Orlando is over. Posters taken down. Exhibits wrapped up and shipped home. Floors swept clean.  After reporting  this event over the years from New Orleans, San Francisco, Orlando, San Diego, Atlanta  we decided to pass on this one.

Despite occasional highlights over the years — the announcement of CALR discoveries, a fiery press conference over Imetelstat’s claims, the bombshell termination of Sanofi’s fedratinib trials, debut of CRISPR for MPN etc. — on-site coverage of these meetings has become progressively more difficult to justify.

Except for reconnecting with old friends, we can get all the important stuff on-line without hassling flights, boarding pets, checking into overpriced hotels, hustling over crowded acres of convention center, hassling shuttle buses and over-booked  restaurants.

And then there’s the shrill explosion of MPN presentations and exhibits accompanied by PR and sales personnel.

Take the Hall of Posters, for example.  At the ASH meeting less than a decade earlier, I believe there were three listed posters covering MPN research. They were supposed to be  tacked up on boards in the Poster Hall.  I can’t be certain. Back then the MPN Poster section was tucked away somewhere in a back alley of that enormous Convention Center. I located what seemed to be the MPN area beyond the Multiple Myeloma section, but I could only find a single MPN poster.

Now there are acres of MPN posters. The Poster Hall is paved with boulevards of MPN posters and eager registrants snapping photos and taking notes as they study the exhibits. Sometimes MPN poster authors hold forth about their research before a small crowd.  MPN posters seem to dominate the Hall and the nearby glittering carnival of corporate  Exhibit space.

What happened? Blame it on a tube of skin cream. And the MPN Gold Rush.

Beyond the sheer number there’s the predictability of on-site MPN abstracts, presentations and posters. Product promotion at the meeting is not limited to the Vegas Strip, the jammed Exhibit Hall with its traffic building free coffee, cookies and bling stands.  When drug companies are footing the bill for production and poster space, marketing is the silent partner of Science wrapped in scientific and academic presentations.

Take one Oral and Poster late breaking Abstract. This one conveyed the results of an Incyte  ruxolitinib study.  Research question:  Do myelofibrosis patients enjoy meaningful changes in the bone marrow environment  as a result of taking Jakafi? To get the answer, researchers took a new hard look at the original COMFORT 1 results and concluded indeed the majority of patient had stabilized or improved results.

Although their conclusions fly in the face conventional wisdom and common sense observation over the past eight years, there’s no arguing with the data.  These are reputable, skilled specialists with deep understanding of the drug.   All six named authors of the abstract either received consulting fees from Incyte and/or are employees or shareholders. 

However, over and over we have seen Jakafi doesn’t inevitably work and normally becomes ineffective after a time. We have witnessed myelofibrosis progress while our friends are on Jakafi, sometimes to acute myeloid leukemia. And sometimes, most painfully, to death.

So while we’re aware of Jakafi’s welcome ability to reduce splenomegaly and improve quality of life, often quite rapidly, we’re also aware of Jakafi’s many and serious side effects, the broadcast of which in packaging and marketing materials, is now required by the FDA.

The narrow selection of confirming data points and presentation of positive conclusions characterize the acres of research reports stretched across the ASH Poster Hall.

Simply put, Drug companies want the work they finance to yield positive resultsMPN investigators want their work to succeed. There is a built-in bias to the process that is far from objective scientific inquiry.  There are no ASH posters or press conferences trumpeting failure of a drug in clinical trial. Our MPN specialists don’t hit the road to present findings that don’t reach their endpoints. Normally, failed products just fade into oblivion without even the tribute of a final clinical trial report.

Can research reporting at large professional meetings be objective?  Maybe.  Will summaries presented by individuals and organizations heavily sponsored by Sponsors of research and clinical trials be biased?   Probably.  No one goes into new drug development project without anticipating – or at least hoping for – success.  And as the stakes go up (a full bore trial of new drug can cost hundreds of millions of dollars), the urgent need for success increases.

Whether or not this bias plays out in reporting is another story.  That rarely means falsifying data. What it does mean is highly selective reporting.  We’ve all witnessed extravagant claims made in press conferences and news releases for one candidate drug or another. Or concentrated focus on a specific medical benefit of a drug.  But we’ve never seen a press conference held to announce failure of a trial.  In a decade of MPN reporting, we have seen several hundred posters in the ASH exhibit space, but not one featuring the failure of a drug to reach its stated endpoints necessary for FDA approval.

Beyond the hassles and reluctance to pay for marketing hype, we had another good reason to avoid the crowds at ASH this year.

Soon enough there will be detailed reporting of major results, new drugs and procedures. We’re already getting preliminary reports.

Well-qualified specialists will pop up on our computer screens with videos, running down the highlights. MPNRF and MPN Advocacy and Education will publish summaries and analyses. Patient Power will flood the Internet with specialists gently interviewed by Andrew Schorr.  On our PCs and phones we’ll see the familiar faces of  Ruben Mesa and Serge Verstovsek cataloging the winners and emerging trends.  Hopefully Claire Harrison will weigh in. (We’re looking forward to John Crispino’s encyclopedic wrap-up in the pages of the MPN Research Foundation newsletter.)  And in coming months a cadre of hematologists will fan out to appear at patient conferences and meetings sponsored by CR&T and MPN A&E among others.

All in all, this cavalcade of communication, along with massive drug company consolidations and whole libraries of MPN scientific papers, is characteristic of our new overheated MPN world.   How did we get from a quiet backwater rare blood disease to the hematopoietic rock star road show we’ve become?

That gets us back to the tube of skin cream.

In the last decades of the 20th Century, a small California company carved out a valuable niche in the growing genomic information business. Using newer high throughput sequencing equipment, it produced and  sold genomic data bases, sequences of genes, and stored DNA fragments to researchers.

In 2000 the new millennium kicked off as Celera and the Human Genome Project produced the first more or less full sequencing of the human genome.  While mostly complete, little was known of how it all came together through  the proteins produced by the expression of all those genes. And with publication of that work, much of the exclusivity enjoyed by  that little company,  Incyte Genomics,  was undercut.

In 2001, Incyte changed course. Several hundred employees engaged primarily in the database business were terminated.  A new CEO, Paul Friedman formerly president of DuPont Pharmaceuticals Research Laboratories, was brought on board.  Losing profitability and its competitive advantage, the company leveraged its genomic strengths to focus on making drugs.  What drugs could profitably combat the legions of genomic disease to which humans are vulnerable?

Fast forward to 2005.  In March, 2005, separate labs in Europe and  the US published the discovery of the JAK2 mutation that, working through the JAK-STAT pathway, seemed to trigger myeloproliferative disorders. Virtually all polycythemia vera patients were found to be positive for that mutation.

  That was interesting to Incyte. They had targeted a much bigger market than a rare blood disease: Rheumatoid arthritis.  (Inflammatory cytokine activity of the JAK-STAT pathway is part of the pathology of rheumatoid arthritis.) But MF could be low hanging fruit.

Those were the early innocent day of myelo matters. The few drugs and procedures available to us were mostly antique – like hydroxyurea, nitrogen mustard and blood-letting– and not backed by giant pharmas with any real interest in us and our low population numbers. Pegasys was around but mostly for unrelated diseases and generally shunned by US hematologists for lack of clinical trial evidence.  And anagrelide, the ET drug for platelet control was around but plagued by serious side effects.

Meantime Incyte researchers, managers and investigators were hard at work in a series of clinical trials.  Nothing much  riveted the MPN community’s attention until the ASCO meeting in the summer of 2011 when Dr. Srdan Verstovsek confirmed positive results of Incyte’s COMFORT trials of ruxolitinib. The drug worked. It would shrink swollen spleens. Myelofibrosis patients might finally have an effective drug.

One week later, MPNforum interviewed Paul Freidman, Incyte CEO.   He was candid about the pathway taken by this MF candidate drug.

Forum: ….I’m delighted that you’re in this game but why? I don’t understand exactly. Am I missing some major point?…  Why enter a relatively small market where there is competition from established therapies, other JAK2 inhibitors in trial now and other genetic trials under way? How did you see this as promising?

Paul Friedman: .We looked at diseases where we thought shutting down JAK signaling would have therapeutic benefit. There’s a list and MF is on the list and we’ll get fairly dramatic results. We have a number of compounds. We took one and put it into RA [rheumatoid arthritis]. Ruxo we felt we would keep in the MPN and broader oncology area.

We have formulated Ruxo although we don’t call it that, we call it 424, as a topical cream for mild to moderate psoriasis. So we thought there were multiple therapeutic areas into which you could go and MF is just one of them and one we felt there was an obvious unfulfilled therapeutic need. And we thought we could develop the drug the quickest So that’s kind of why we went into it.

MF, frankly, we thought would be the quickest path to a first approval ….

We formulated Ruxo although we don’t call it that, we call it 424, as a topical cream for mild to moderate psoriasis. So we thought there were multiple therapeutic areas into which you could go and MF is just one of them and one we felt there was an obvious unfulfilled therapeutic need. And we thought we could develop the drug the quickest So that’s kind of why we went into it..

That was eight years ago. Today variants of this psoriasis skin cream morphed into Jakafi, an MPN drug barreling along at the rate of  $1.4 billion annual revenues and accelerating. In just  the first six months of 2019 , Jakafi piled up over $785 million dollars in revenues, up 19% over 2018

Over time, Incyte became the MPN paymaster.  Many of the  US clinical trial investigators and their institutions, MPN nonprofits and associated commercial media,  have gotten substantial grants and support from Incyte...  Jakafi didn’t achieve its billion dollar + status without generous distribution of cash. Or without the cooperation of the MPN medical establishment and support organizations. And that too is characteristic of the new MPN world.

Incyte’s successful creation of Jakafi fueled the race to produce another JAK2 inhibitor that would dominate MPN research — financially and scientifically.   YMI Biosciences, Targegen, S*Bio, CTI,  Novartis,  Sanofi, Gilead, BMS, all piled on.  Now that the mighty Big Pharma industry became aware of the revenue potential, the MPN world no longer be the quiet hematologic backwater it had once been. .

What is truly amazing are the limitations as well as the benefits of this drug that changed the MPN environment.   Jakafi is a drug with fairly unknown and unpredictable biological activity. It normally ceases to be effective after a time due to persistence of the mutant JAK2 clone.  It has a good record in spleen reduction and short-term improvement of quality of life.  Despite claims to the contrary it has no effect on the progress of myelofibrosis and has both durable and severe side effects. In some settings, it might be considered a short term drug to prepare patients for stem cell transplant or improvement of clinicals prior to a course of the slower acting, more effective interferons. And at $10,000+ plus a month it is a hefty contributor to the bankruptcy of the US medical care system.

It makes no difference.  The Gold Rush is on. Myeloproliferative neoplasms are now big business with the money, research, publications, posters exhibits and papers to prove it.

Take TargeGen, creator of a JAK2 inhibitor on the same track as Jakafi.  The company was acquired by Sanofi which sponsored a full blown international clinical trial of Fedratinib. On the eve of filing for FDA NDA approval, Sanofi’s  Fedratinib unceremoniously pulled the plug on the trial on reports of death and injury due to Wernicke’s encephalopathy (WE) and a temporary suspension by FDA.  All patients were instantly booted off the trial with no compensation and little more than advice to have their thiamine levels checked.

Despite the bad odor of its demise, Fedratinib had some good results among participants in the clinical trial. It lay dormant for a couple of years until further research indicated  WE may not have been caused by the drug and was, in any case preventable. San Diego Drs John Hunt and Catriona Jamieson acquired the rights to Fedratinib  setting up Impact Biomedicines and almost instantly flipped it over to Celgene which paid a reported $7 billion for the acquisition based on milestones and sales performance. Celgene filed for FDA approval after one clinical trial.. They got it,  with a serious Black Box warning,  and, renamed Inrebic became the second approved MF drug.

.Last month Bristol Myers Squibb completed acquisition of Celgene for a reported $74 billion

Striking gold!

Targegen founded in 2002 (during the “old” MPN era”) with just a handful of employees, was acquired by Sanofi for $560 million in 2010 (the “transitional” MPN era). Acquisition of Celgene by BMS for $74 billion  may be the clearest hallmark of the “new” overheated MPN era.

Significantly , whether or not any other JAK inhibitor is measurably equivalent or better than Jakafi we’ve known from the beginning that the JAK2 v617f mutation  may drive proliferation but it is not the root cause of myelofibrosis.  Jakafi is equally effective in reducing splenomegaly in MPN patients who have the mutation and those who do not have the mutation.  And the JAK2 mutation is found in the general population without producing any of the MPN phenotypes.

The effect of the Jakafi revolution on the international MPN community

The search for another billion dollar payday has siphoned billions of dollars and countless person-years of research time away from fundamental scientific MPN research without much to show for it.  MPN specialists serving myelofibrosis patients and thousands of MF patients were targeted in Incyte’s multi-pronged marketing.  Regardless of its limitations, JAK2 inhibition had become the prime objective of MF new drug research.

Observing the Jakafi effect on the MPN community from the very beginning, we are ourselves biased. The relief of painful splenomegaly and improvement of QOL has led advanced MF patients to defer stem cell transplant to the point where they either suffer progression to AML or are so debilitated as to no longer quality for the only curative procedure available to MF patients. Recently, two of our close friends and strong supporters of the MPN community died under those conditions.

There are times to wisely choose a JAK inhibitor…and times to refrain from choosing one.  The choice can be a matter of life and death and sorting out our options requires some intensive study and discussions with trusted physicians and patients.  The FDA approval of Jakafi for polycythemia vera after the conduct of a badly designed trial illustrates how difficult it is to chose wisely.

Meantime, away from the official ASH annual meeting hoopla, there is one final crusade worth suiting up for: Education. Learning and sharing can be the life and death difference for each of us. We may be dealing with pain, uncertainty and conflicting therapeutic claims sloshing around in a money contaminated environment but there are still good people and organizations reaching out to help us. Ann Brazeau of MPN Advocacy & Education, Andrew Schorr’s Patient Power and Michelle Woerhle and her team at the Foundation may all be recipients of Incyte grants but their hearts are with MPN patients and their reporting outstanding.

Finding and consolidating our support networks and reaching out to new MPN patients who are lost in the contentious seas of alternative therapies is essential to strengthen our MPN community. To place an individual’s experience in the historical context of MPN treatment options might help provide much needed clarity.

And providing supportive buddy services, the way MPN patients like Chris Harper have been doing for stem cell transplant patients would assure no one needs go through their MPN journey alone,  Good luck…and Happy New Year.


The good news from Orlando:  the  Age of Genomics has finally dawned over the MPN landscape…

Distant from Big Pharma’s boardrooms and legal offices, scientific laboratories are bringing home the curative  promise of gene editing.
These three late-breaking abstracts from the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando report continued success against blood diseases.

December, 2015 — MPNRF and MPNforum produce the CREATE seminar at ASH to explore CRISPR, stem cell transplant and MPN research. Today it’s a reality.


Most of us let our eyesglaze over when we run across scientific and technical reports, particularly when they don’t relate to our specific myeloproliferative neoplasm. As a means of making wise therapeutic treatment choices this is not a good strategy.   Most drugs used to treat MPNs are approved for other pathologies. Our workhorse meds like hyroxyurea and interferon are presecribed for us off label. They can be effective because biological systems share many pathways and signal responses.

B-ALL, AML and myelodysplastic syndrome, AML and Sickle Cell, for example, are second cousins to MPNs, We share the same bone marrow, myelo blood cell place of birth but different development paths.  More importantly, the immunotherapy techniques employed to relieve symptoms and produce minimal residual disease (cure) apply directly to MPNs.

Here are the details but the bottom line is stark and compelling. Since the arrival of CRISPR, greatly accelerated gene editing, immunotherapy – using a patient’s own modified immune system to attack and neutralize the effect of pathological mutants – has  exploded. The results reported today just confirm how inexorably genetic research and immunotherapy are colluding to repair devastating blood diseases.

Press release: Immunotherapy Superior to Chemotherapy for Children with Relapsed B-ALL
LBA-1: A Randomized Phase 3 Trial of Blinatumomab Vs. Chemotherapy As Post-Reinduction Therapy in High and Intermediate Risk (HR/IR) First Relapse of B-Acute Lymphoblastic Leukemia (B-ALL) in Children and Adolescents/Young Adults (AYAs) Demonstrates Superior Efficacy and Tolerability of Blinatumomab: A Report from Children’s Oncology Group Study AALL1331.

Press release: Study Reveals Genetic Underpinnings of AML and Myelodysplastic Syndrome
LBA-4Integrated Transcriptomic and Genomic Sequencing Identifies Prognostic Constellations of Driver Mutations in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Press release: Encouraging Results Seen with Novel Approach to Gene Therapy for Sickle Cell Disease LBA-5Validation of BCL11A As Therapeutic Target in Sickle Cell Disease: Results from the Adult Cohort of a Pilot/Feasibility Gene Therapy Trial Inducing Sustained Expression of Fetal Hemoglobin Using Post-Transcriptional Gene Silencing

The CRISPR fix that
could combat blood disorders. (From Nature).
Researchers have finally identified a reliable way to edit the genes of blood stem cells.

Gene editing at The Hutch
successfully targets blood stem cells.(ScienceDaily)            

MAGIC..Myelofibrosis Risk Assessment Tool + The 15 Top MPN Mutations…

Now we have a simple, powerful tool to convert our basic clinical data into a clear graphic signal to highlight our status. Sponsored by the MPN Research Foundation, MAGIC (Myelofibrosis Assessment Graphic Internet Calculator) is clinically validated and produced with the help of an international consortium of 10 scientists and hematologists plus MPN patients and patient advocates. Dr. Claire Harrison, Dr. Ruben Mesa, Dr. Richard Silver, Dr. Srdan Verstovsek, Dr. Koen Van Besein, Dr. Nicolaus Kroeger, Dr. Jeanne Palmer, Dr. Uday Popat, Dr. Attilio Orazi, Dr. Wael Saber, Chris Harper, Beatrice Larroque, Martin Prager, Ann Brazeau, Ann Haehn, Barbara Van Husen, and Zhenya Senyak.

Pop in your numbers and press the button!

MAGIC is free and it’s here.


It’s a beginning but did The MPN Patient Bill of Rights get it wrong? There’s a mix of good intentions and missed opportunities in the MPN Patient Bill of Rights produced by a handful of well-meaning patient advocates and nonprofits.  In some respects the new MPN Patient Bill of Rights misses the point…. Even if it had teeth (it doesn’t) none of its provisions would have spared us Sanofi’s brutal boondoggle of a Fedratinib blow-up or revealed Jakafi’s hidden dangers unmasked by the FDA….The “MPN Bill of Rights” basically grants us the right to be informed, to be an educated consumer of medical services.  Yes it does note our rights to privacy, to get a second opinion, the right to seek financial aid, to access information and bring family and friends to consultations.  All good stuff but still  pretty passive.  And, in an outright sour note, the document itself, printing of which is sponsored by Incyte Corporation, also grants us the right to access clinical trials and participate when we’re eligible..

What’s not granted is: Our right to be included as an active and equal participant in exploration of our treatment options… Our right to be alerted to the secret dangers of prescription drugs…Our right to know the hidden risks and personal costs of clinical trial participation…And most desperately needed, the right to have a patient advocate on every MPN clinical trial. (something for which over 1000 of us petitioned the FDA and were granted.)…What the MPN Bill of Rights basically doesn’t grant us is an equal, dignified and respected say in our own treatment,.


Updated, December 15…  List of 300+ Patient-Recommended Hematologists from 27 Nations & 47 States

The MPNclinics – 302 answers to 141 Patient questions… with Index

Stem cell transplant — Six front-line stories and some vital links.

THE ARCHIVES:  A Visual Catalog of MPNforum Articles.

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