To be aware…
- -Zhenya Senyak
I didn’t publish my report to terrify patients by listing the health risks of Jakafi .
I published it to raise awareness of Jakafi’s acknowledged health impacts and help neutralize the sense that Jakafi is a safe miracle drug that will provide durable relief from our MPN symptoms.
I have seen the comments on my Jakafi posts and articles. I regret any unnecessary alarm it caused and am deeply grateful to the reader who recognized it takes courage to be the bearer of bad news. Sounding this warning was sure to antagonize many friends, MPN patients and caregivers and even some physicians who rely on approved standards of care.
Those who are taking and prescribing Jakafi need to believe it is effective and safe. Those who are thinking of taking it in future want to believe it will work for them without causing health issues. And Jakafi does work, it can stabilize counts, reduce swollen spleens, improve quality of life…over the short term. It’s not a miracle drug. It won’t tidy up our office, floss our teeth, or cure us of myelofibrosis.
But it comes with a cost. It can hurt us. It can kill us. We don’t get that message often or clearly enough.
It took Incyte’s successful attempt to extend its market into the PV sector and its near sham of a clinical trial to wake me up. It took the death of a dear, close friend, a man I relied on for many things in this life, to shock me awake. And it took a letter from the FDA to help me understand the underlying realities of Jakafi.
My friend with PV took Jakafi to relieve his associated symptoms. He rapidly transited to myelofibrosis and then with astonishing speed to acute myeloid leukemia. He did not survive a salvage stem cell transplant
I stumbled on the specific known risks of Jakafi as a result of reporting on the Incyte RESPONSE trial that resulted in the approval of Jakafi for polycythemia vera in patients in whom hydroxyurea is not an option. In response to my article and repeated letters, an FDA spokesperson sent me a copy of its letter to Incyte requiring specific language about risk to appear in packaging and promotional materials The FDA further required clinical trials to establish the long-term safety of Jakafi.
Based on Incyte’s own required statements, at least a dozen or so separate disease risks arise from Jakafi use. Beyond that, there’s the most deadly possibility: The masking of advancing disease until a stem cell transplant is no longer a viable option.
Jakafi’s target and unintended consequences.
The mutation: This is a somatic mutation – that is, an acquired mutation that arises in our life, not programmed at conception. In the reproductive shuffling of DNA, translocation of amino acids happens all the time. This time, when the event occurred on the short arm of chromosome 9, it switched blood production into overdrive. JAK 1 and 2 use a biochemical pathway to signal DNA to produce blood,. The mutated JAKs signal much more blood production than needed for survival.
The effect of this mutation, multiplied through succeeding generations of blood producing stem cells, is enough to create polycythemia vera and impacts other MPNs. Blocking this mutation – inhibiting the JAK2 mutated gene – relieves the overproduction problem…and thus creates the cytopenias like anemia and low platelet production while relieving the spleen of its blood storage and production roles. Some cytopenias can be successfully treated.
The unintended consequence: Another effect of blocking this mutated gene is to restrict production of a significant part of our immune system which also arises in the blood-producing stem cells, including our Natural Killer cells, B cells and T cells..
As a result bacterial and viral diseases have a chance to take hold and the brakes can be removed from the natural progression of an MPN disease.
Hepatitis B, herpes, tuberculosis. non-melanoma skin cancer are among the Jakafi disease risks that Incyte has reported. Others have reported possible development of additional High Risk Mutations. To complete our risk assessment, we need to know the incidence of these Jakafi related events and how likely severe adverse effects will impact us.
And then there’s the most deadly possibility: Jakafi’s masking of advancing disease until a stem cell transplant is no longer a viable option
With all this in hand, I shared my findings with the MPN community. Was there another option?
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