International MPN News, Science & Opinion

The HU INF Addendum – Trials, Pricing, Resources

 

huint logo full

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 therapydivider horizon lineIn 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.

divider horizon line

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.

divider horizon line

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.

NCT01949805Pegylated 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

NCT01259856Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea in Polycythemia Vera (PV) and Essential Thrombocythemia (ET), Ronald Hoffman,  MPD-RC, Mt. Sinai School of Medicine. Phase 3 recruiting, partially entrolled. Est. anticipated enrollment: 300.
https://clinicaltrials.gov/ct2/show/NCT01259856?term=hydroxyurea+versus+interferon%5C&rank=2
 
NCT01387763Danish Study of Low-dose Interferon Alpha Versus Hydroxyurea in the Treatment of Philadelphia Chromosome Negative (Ph-)Chronic Myeloid Neoplasms (DALIAH), Thomas Stauffer Larsen, Odense University Hospital Phase 3, on-going not-recruiting, anticipated enrollment: 300.
https://clinicaltrials.gov/ct2/show/NCT01387763?term=hydroxyurea+versus+interferon%5C&rank=3
divider horizon line
Selected resource materials

Holly Geyer, et al. in Blood, Unmet Needs for Symptom Control in Essential Thrombocythemia with Front Line Therapy 

Dr. John Mascarenhas et al., HaematologicaOptimal 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 MPNsfrom The Interferon Papers 2.

MPNforum The Interferon Archive, featuring Patient Power interview with Dr. Richard Silver at ASH.

 

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: