Special Report: Trials, Pricing, Resources
Despite real innovations in development – notably gene therapy and immunotherapy – right now and in the near-term future we have no radical alternatives to HU and INF for treatment of polycythemia vera and essential thrombocythemia. These two drugs, neither of which is FDA approved for use in MPN therapy, are prescribed at one time or another, alone or in combination, for the great majority of MPN patients. (Anagrelide, agrylin, is a potent drug targeting high platelet levels and has been implicated in severe side effects.)
Front line therapy
In general, front line treatment for ET, PV and certain presentations of MF is hydroxyurea or interferon. * One or the other will work for some of us, some of the time. Our age and risk status will certainly be taken into account but our choice boils down to determining which of these two drugs is likely most effective for us while posing the lowest short and-long term risk.
- There is another option thanks to FDA approval of Jakafi for PV use last year in a deeply flawed clinical trial. Jakafi ($10,000/mo.) was pitted against Best Available Therapies in a PV trial that recruited patients for whom HU (about $30- $60/mo.) had already failed or for whom HU had proved refractory. The great majority of investigators in this trial selected HU as the drug to compare wth Jakafi.
For MPNs at all risk levels HU, for historic and economic reasons, is in far greater use than interferon but the gap is narrowing. Beyond historic and traditional factors, a critical restriction on expansion of interferon use is relative pricing of the two drugs and insurance company reluctance to approve, particularly in the absence of FDA approval.
Comparative retail prices
60 capsules of hydroxyurea 500mg About $30 – $60
1 kit (4 syringes) of Pegasys 180mcg/0.5ml Usually once per week. About $4000
1 vial of Intron A 10 million IU $250 Injection, three times per week. About $3000/mo
There’s another financial obstacle. MPNs are generally a disease of older adults and many ET and PV patients qualify for Medicare. While Hydrea of hydroxyurea is a Tier 3 drug (Medicare patients generally pay about $45 for a monthly supply) interferon in either Intron A or Pegasys formulation is a Tier 5 drug requiring patients to pay 33% of the cost.
Since there is such a jungle of medical insurance plans available in the United States and various government and private programs to help cover drug costs, the actual out of pocket cost to any individual patient varies greatly.
The current trio of comparative clinical trials comparing the two drugs – AOP Orphan Pharmaceutical PROUD-PV study, the Danish DALIAH study , and MPD-RC Pegasys vs. HU study– will all report results at ASH and present posters. But they’re not going to be game-changers. And the results will not be surprising. AOP didn’t spent millions of dollars to prove its variant of pegylated interferon is not effective. The Danes have been using interferon successfully for decades. And the ambitious but incompletely enrolled 30 country MPD-RC trial will have only partial, provisional data to report. Still we will get a verified statistical handle on which to hang the accumulated anecdotal evidence emerging from decades of clinical experience.
These are the trial results we’ll be scrutinizing come December.
NCT01949805, Pegylated Interferon Alpha-2b Versus Hydroxyurea in Polycythemia Vera, (PROUD-PV) AOP Orphan Pharmaceuticals AG. Phase 3, completed. Enrollment: 256.
https://clinicaltrials.gov/ct2/show/NCT01949805?term=hydroxyurea+versus+interferon%5C&rank=4
https://clinicaltrials.gov/ct2/show/NCT01259856?term=hydroxyurea+versus+interferon%5C&rank=2
https://clinicaltrials.gov/ct2/show/NCT01387763?term=hydroxyurea+versus+interferon%5C&rank=3
Holly Geyer, et al. in Blood, Unmet Needs for Symptom Control in Essential Thrombocythemia with Front Line Therapy
Dr. John Mascarenhas et al., Haematologica, Optimal therapy for polycythemia vera and essential thrombocythemia …
The MPN Drug Wars, by Jeremy Smith
Dr. Hans Carl Hasselbalch: Response to attacks on interferon, an Open Letter
How I treat MPNs, MPN Quarterly, Harrison, Silver et al.
Dr. Olatoyois Odenike discusses why hydroxyurea is the first line therapy option in the United States for essential thrombocythemia instead of anagrelide or interferon.
Dr. Claire Harrison on the importance of these trials
Richard Silver: Bringing interferon to MPNs, from The Interferon Papers 2.
MPNforum The Interferon Archive, featuring Patient Power interview with Dr. Richard Silver at ASH.
MPNforum Magazine 
Comments on: "The HU INF Addendum – Trials, Pricing, Resources" (3)
As one with a background in integrative medicine, having read the research…, I am opposed to considering Hydroxyurea or Jakafi (coke or pepsi) for my recently diagnosed PV. Interferon seems to me to be by far, the right choice along with Traditional Chinese Medicine. My insurance is Medicare, how can I get approval for interferon?
There is a place for both HU and ruxolitinib in MPN therapy but I agree with you that the interferons are a better therapeutic option at early stages of disease and when reduction of splenomegaly is not an immediate concern. Many MPN patients have had success using these links to obtain insurance coverage by forwarding them to their hematologists/.physicians and having strong and persistent discussions. It’s too bad we have to work so hard since HU is prescribed off label as well as Jakafi has serious side effects. Good luck.
https://mpnforum.com/an-open-letter/
https://mpnforum.com/the-interferon-papers-part-iii/
https://mpnjournal.org/how-i-treat-mpns-2/