International MPN News, Science & Opinion

The Senyak Report

Anagrelide on the watch list…

Will Novartis blink?  How much is a year of life worth?…

 New hope for early access to experimental drugs…

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Anagrelide (Agrylin) has been placed on the FDA Watch List.

The FDA is finally (sort of ) taking action on something we’ve been complaining about for years… But don’t throw out your prescription yet. The FDA Watch List is just that… an advance warning system alerting us of potential safety issues.  It’s the FDA Adverse Event Reporting System (FAERS) in action.

FDA Anagrelide warning

The adverse event tagging Anagrelide — a favorite of some hematologists to bring down platelet levels and an approved treatment option for ET since 1997 — is something called torsade de pointes,  or simply torsade. This is a cardiac condition causing ventricular tachycardia.

Cardiac issues may be rare by FDA standards but cardiac effects are far from rare among MPN patients who have taken Anagrelide.  And there is ample warning to that effect in the drug’s precautions advisory.   (My own exposure to Anagrelide was so heart thumpingly bad I went off the drug after a few weeks.  I suffered damage to my A/V node, a cardiac connection that permits communication between the upper and lower chambers of the heart.  Eventually, I had a pacemaker implanted.)

For now, we need only be aware of the Anagrelide status and make sure our hematologists know what’s going on.  Changes in dosage regimens and increased experience with the drug have produced good results in some MPN patients. You can access the full FDA document here and maybe print out a copy for your doc if you’re currently on the drug.

Note: The appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk. It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk

dots cml cropped Will Novartis blink?

Short-term outlook grim for UK MF patients on Jakafi but help may be on the way…

Novartis HQ, Basel Courtesy ArcSpace.com

Novartis HQ, Basel
Courtesy ArcSpace.com

Now that the National Institute for Health and Care & Excellence (NICE) of the UK has refused to recommend Jakavi on the National Health Service , will Novartis back down and drop its price for the MF drug?  The giant drug maker, which has previously lowered prices in response to similar actions on some of its other drugs, has so far made no move.

“Terribly sorry,” in effect, said the Brit regulators  “since it works and all that but it’s too damned expensive.”

Sir Andrew Dillon, chief exec of NICE, did actually express “disappointment.”   NICE concluded: “Jakavi was clinically effective in reducing spleen size and symptoms, such as itch and fatigue, but “limitations” in Novartis’ economic model meant there were uncertainties in the drug’s cost-effectiveness.”

Quality of Adjusted Year Life

Those limitations are a sore point with both patients and the medical community since they’re based on an almost Orwellian calculation of cost effectiveness based on QALY or Quality Adjusted Life Year.   So, how much is a year of your life worth?

The calculation varies based on the state of a patient’s health, age, condition…with “adjustments” consisting of points off for illness, disabilities, etc.  Presumably, somewhere in the final  calculation,  is the relative cost of extending that life compared to the return on medical investments in other therapies. “We have to be sure,” said Dillon,” that the treatment is both clinically and cost effective, because money has to be diverted from elsewhere in the health service to pay for it.”

Novartis claims Jakavi costs £74,000 and £57,000 per quality adjusted life year (QALY) gained.  NICE says the number is more like £149,000 per QALY gained.  (Health Today reports Jakavi costs £3,600  ($ 5,600) for a 60-tablet pack, corresponding to an annual cost of approximately £43,200  per patient). … With new, possibly more targeted, JAK inhibitors nearly ready to come on stream — notably Sanofi’s 302503  and CYT387 — it’s hard to believe Novartis won’t offer NHS a steep discount but waiting for this stand-off to play out makes for a  a jittery time for UK MF patients.

Asking patients how much they would pay for a QALY may not be too instructiveA 2005 study published by NIH’s PubMed surveyed 391 patient populations and came up with a range of $12,500 – $32,200 in 2003 US dollars. Since responses are qualified based on personal economic circumstances and the impact of disease on an individual’s life, the range is not surprising. Placing a dollar value on human life remains a strange and hopeless task.  Clearly impoverished individuals as well as emerging nations with more limited capital resources would be forced to allocate much smaller amounts for a QALY…thus making economic status the the chief consideration in valuing human life.

Maybe it’s not so much a question of Novartis blinking or NICE backing off but the willingness of regulators, patients, healthcare providers and corporate players in the medical business to turn a blind eye to the greed, inequities, bad judgment, predatory pricing and outright corruption that drives drug and medical care prices to levels that bankrupt individuals and nations alike.

This final NICE draft guidance will be followed by a Final Guidance to the NHS next month which could essentially remove the Jakavi option from NHS patients and those medical groups in the UK normally following NICE recommendations.

Related:

Will Jakafi be priced out of the UK market? (This is an MPD Voice story and commentary by Dr. Claire Harrison pubished in MPNforum in March:  https://mpnforum.com/2013/02/18/will-jakafi-be-priced-out-of-the-uk-market/

News release from NICE:   http://www.nice.org.uk/newsroom/pressreleases/NICEPublishesFinalDraftRecommendationsNewTreatmentForEnlargedSpleenAdultsWithRareBloodCancer.jsp

The Jakafi Report (MPNforum) https://mpnforum.com/the-jakafi-report/

A PatientPower interview with Dr. Claire Harrison on the impact of JAK2 inhibitors and combination therapies http://www.patientpower.info/video/improving-a-breakthrough-combination-therapies-with-jak-inhibitors?autoplay=1

The Incyte Annual Report is now on-line.    By some reports, nearly 10,000 patients — on trial and in private clinical use — have now been on Jakafi therapy. What’s the bottom line impact?  In photos and numbers, here’s the official tally.

dots cml cropped  Can we get an experimental drug when we need it?

There is some FDA clarification on the therapeutic use of investigational drugs that have not yet proven their safety or efficacy.

Why this matters to us.   When we run out of good treatment options and our condition warrants it, we can often head for a clinical trial. But many trials are closed or at early Phase I/II dosage and toxicity stages…And even if we qualify for an open Phase III double blind trial, we can’t be sure we won’t get stuck on the placebo arm.

There may be a solution.  We can ask for a special dispensation to get the drug.  Or our physician can.

The FDA has long favored access to investigational drugs for treatment  ” for patients with serious or immediately life-threatening disease or conditions who lack therapeutic alternatives.”  The problem has been clearing the bureaucratic hurdles to get those drugs.

The guidance is designed to simplify the process. This non-binding draft  guidance represents current FDA thinking in cases where there is an Investigational New Drug (IND)  trial in place as well as those instances when no IND is in effect or the Sponsor (the drug company) declines to open such access. In either case the requirement falls on the patient’s physician to request therapeutic use of an investigational drug. IND. The FDA guidance on this is both logical and straightforward:

“The patient’s physician must determine that the probable risk to the patient from the investigational drug is not greater than the probable risk from the disease or condition The patient’s physician should make this determination based on the information about the drug available to the physician and the physician’s knowledge of  the patient’s clinical situation”

For questions regarding this draft document contact FDA departments at Center for Drug Evaluation and Research,  Colleen Locicero at 301-796-2270 or the Center for Biologics Evaluation and Research, Office of Communication, Outreach and Development at 800-835-4709 or 301-827-
1800.

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM351261.pdf?source=govdelivery

–  #30  –

Take me back to the Contents

© Zhenya Senyak and MPNforum.com, 2013. Unauthorized use and/or duplication of this material without express and written permission is prohibited. Excerpts and links may be used, provided that full and clear credit is given to MPNforum.com with appropriate and specific direction to the original content.

Comments on: "The Senyak Report" (1)

  1. Mercedes Maharis MA MS MA said:

    Hi, Zhen,

    Well… the FDA hit list on Anagrelide has me worried… plus your experience.

    I’ve dealt with thumping and palpitations for years… was in Agrylin trials in 94 before it was approved! In the trials!

    But, I’m still alive. I had hives with Hydroxy Urea, so Agrylin saved my life… platelets 1,800,000.

    Now what? Get a nuclear stress test with Halter follow up from my cardiologist to see if there is damage? Ay, ay, ay!

    Ignore it until the FDA final ruling comes out? When will that be?

    Sorry about your pacemaker. You are remarkable to continue with this wonderful MPN Forum… THANKS!

    I’ve emailed this to Dr. Rosenbloom in Beverly Hills.

    He’s been treating me since the ’94 trials for AG and I trust him totally.

    Went to see him in April… he put me on an aspirin, 81 mg for the first time in conjunction with .5 mg Agrylin 2 X daily… He wrote back to say that if AG is taken off the list he would put me on another med… but, that I’m doing well, so stay on it.

    I’m 70 now and thankful to have had these years, at least…

    So, what next! Life is an amazing journey!

    Knowledge is power, so thanks so much again for this new knowledge again!

    Mercedes

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