Entresto Goals

Discussion in 'Novartis' started by anonymous, Aug 17, 2015 at 10:18 AM.

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  1. anonymous

    anonymous Guest

    Accurate post. For the cognitively impaired person you responded to.. look at ATLAS, CONSENSUS and SOLV-D.. noted no difference in outcomes. Only 28% of patients could tolerate high doses vs 80% tolerability rate, without any differencea in outcomes. He/she doesn't understand law of diminishing returns. Just chooses to shout out empty talking points like an empty-suited politician. You can't fix stupid, I guess..
     

  2. anonymous

    anonymous Guest

    Entresto has been pulled from the market! It's all over the news. Higher death rates or something. OMG, how are we going to spin this?
     
  3. anonymous

    anonymous Guest

    Wow !! They just discovered diovan-tresto can ALSO be used to treat hypertension !!!!
    What a stunning revelation !!!!!! This changes ...EVERYTHING !!!!!!! :rolleyes:
    "LONDON — Valsartan/sacubitril, formerly known as LCZ696 — but now bearing the brand name Entresto since it won FDA approval for heart failure — may also be a potent treatment for isolated systolic hypertension"
     
  4. anonymous

    anonymous Guest

    Or you can sell cheap generic valsartan for ISH at about $200 yearly vs untrusto for $4500
     
  5. anonymous

    anonymous Guest


    You heard it here first.
    Entresto will bring in > $10Bn/year during the peak of its lifecycle:


    Lowering blood pressure below a commonly used target significantly reduced serious heart problems and cut the risk of death in adults aged 50 and older, preliminary results of a large government-sponsored study showed on Friday.

    In the study of more than 9,300 patients with hypertension, using a combination of medicines to reduce systolic pressure to a target of 120 cut the rate of heart attacks, strokes and heart failure by almost a third, and the risk of death by nearly a quarter, compared to target of 140.

    "This study provides potentially life-saving information that will be useful to health care providers as they consider the best treatment options for some of their patients, particularly those over the age of 50," Dr. Gary Gibbons of the National Institutes of Health, which sponsored the study, said in a statement.

    http://www.reuters.com/article/2015/09/11/us-health-bloodpressure-idUSKCN0RB1TJ20150911
     
  6. anonymous

    anonymous Guest

    The vast majority of blood pressure medicines from a variety of classes are available as inexpensive generics. The classes include angiotensin receptor blockers, or ARBs, such as Novartis' Diovan, calcium channel blockers, like Pfizer's Norvasc, ACE inhibitors, including Pfizer's Altace, and diruetics, such as Merck's Hyzaar.
     
  7. anonymous

    anonymous Guest

    Do we make sildenafil?
     
  8. anonymous

    anonymous Guest

    It's another Nofartis stinker!
     
  9. illusion

    illusion Guest

    SEP 14, 2015 @ 09:42 AM 2,818 VIEWS
    Is The Superiority Of Entresto Just An Illusion?
    Entresto, a combination of an old drug valsartan with a novel neprilysin inhibitor sacubitril fromNovartis , which was approved in July for treating heart failure, has been ear-marked by analysts as a mega-blockbuster. Some suggest $10 billion per annum peak sales may be achievable, making it one of the biggest selling drugs of all time.

    A 20% reduction in mortality among people with advanced heart failure (as many as 3 million people in the U.S. alone) certainly grabbed the headlines. And at a list price of $4,500 per annum (about ten times the cost of the current, generic, standard of care), payers are already rattling sabres.

    But is Entresto really a breakthrough in the care of heart failure patients? And can it possibly justify such a price premium?

    High-price drugs have spent much of the last five years in the glare of public attention. Initially, it was the eye-watering costs of drugs for ultra-rare conditions, such as Soliris eculizumab from Alexion, used to treat paroxysmal nocturnal haemoglobinuria (PNH) and costing $500k for a year’s treatment, that propelled drug prices into the mainstream debate.

    Then Gilead’s HCV drug, Sovaldi (and its follow-on combinations), costing $86k for a 12-week treatment course, was approved to address a much more common condition. With a million or more patients in the U.S. alone who would benefit from it, there has been genuine concern it could break Western healthcare systems altogether, resulting in restrictions that prevent all who would benefit from accessing the medicine.

    But the budget-busting champion may eventually be Entresto. Though cheaper, by some margin, than these other drugs (at $4,500 per annum, it is only 1% of the cost of a course of Soliris, for example), the size of the treatable population according to its approved label dwarfs the others, at least until the PCSK9 antibodies win a broader label with cardiovascular outcome data due at the end of 2017.

    Indeed, for many medicines that have commanded a high price in recent times, the degree of efficacy has been such that it is unclear whether the price, though numerically large, is really excessive. A crude comparison between the cost of an early prophylaxis against smallpox in the 1750s and Solvadi in 2014 suggested the perceived value of a curative against an otherwise fatal disease has remained remarkably constant across centuries and continents.

    But in this regard, Entresto is also an outlier. It is nothing even resembling a cure.

    A quick review of the clinical trial data is pretty straightforward: Entresto was approved on the basis of a single, large Phase 3 trial called PARADIGM-HF, in which 8,442 patients were randomized to the Entresto combi-pill, or to an active “standard of care” arm consisting of the ACE inhibitor enalapril. The trial was stopped early by the data monitoring committee, and the evidence of superiority was unequivocal. The primary end-point (a combination of cardiovascular death or first hospitalization for heart failure after treatment commenced) was significantly less frequent in the Entresto group (the hazard ratio was 0.80, meaning the chance of harm was 20% lower in the Entresto group, with a p value less than 0.001).

    That Entresto is superior to 10mg of enalapril twice daily in this patient population is beyond doubt. But what does it really mean in the real world?

    Firstly, while ACE inhibitors are the recommended first-line therapy for the majority of individuals in this patient population according to the 2013 AHA treatment guidelines, a significant minority would have received alternative treatment combinations outside the clinical trial setting. Moreover, even among those treated with enalapril, some at least would receive 20mg twice daily as opposed to the 10mg dose used in the PARADIGM-HF comparator group. In short, the comparator group in PARADIGM-HF, being a “one-size fits all,” likely did worse than real-world standard of care.

    From a simple, clinical perspective one could argue that doesn’t matter much: a “one size fits all” regimen with Entresto was better, so why not use that? But from a pricing perspective it matters a great deal. If the Entresto regimen (at $4,500 per annum) was actually only the same as can be achieved with a tailored selection of generic medicines at a tenth of the cost, then the price premium is clearly not justified.
    econdly, Entresto is a combination of two agents: one, valsartan, was itself a mega-blockbuster for Novartis, racking up annual sales in excess of $6 billion as Diovan prior to its patent expiry in 2012, and is now available as a generic at less than a dollar a day. The other is a new molecular entity, the neprilysin inhibitor sacubitril, a first-in-class agent not previously approved for any indication. Since angiotensin receptor blockers (ARBs) like valsartan have been used as first-line treatment for heart failure, and have shown significant benefit in clinical trials, it’s reasonable to wonder how much of the benefit of the combination is due to the valsartan. If most or all of the benefit could be achieved with dollar-a-day valsartan, once again the price premium for Entresto would be hard to justify.

    Unfortunately, though, because PARADIGM-HF was performed with an ACE inhibitor as the comparator, we don’t have a definitive answer to this question.

    In the FDA briefing documents, the clinical reviewers also speculated around this question. Although they concluded that a contribution towards the efficacy from the sacubitril component was likely, the magnitude of the contribution remains impossible to quantify without a direct comparison. With the approval of Entresto, however, it is unclear whether such a study will ever be performed.

    Once again, though, clinicians and payers alike are left without the necessary information to estimate the true cost-effectiveness of Entresto.

    Thirdly, there is the question of the absolute benefit to the individual patient. A 20% reduction in cardiovascular mortality during the median follow-up of 27 months in PARADIGM-HF sounds impressive. But those deaths are delayed a little rather than prevented. A reliable extrapolation of the Kaplan-Meier curves suggests at most a 6-month median benefit (which, as noted above, is already likely to be an over-estimate of the true benefit of Entresto versus an optimal standard of care using generic drugs).

    Given that NYHA stage II-IV heart failure with ejection fraction below 40% (the criteria for enrollment into PARADIGM-HF) has a median survival less than 5 years, it bears comparison with many cancers in terms of the mortality burden. High-priced cancer medicines that delay progression by a few months, but do not represent a cure, have also come in for considerable criticism.


    Unlike Soliris or Sovaldi (and perhaps even Repatha and Praluent, although hard evidence of their real efficacy on cardiovascular events has yet to be collected), Entresto is no miracle cure. On the other hand, it certainly does have efficacy – PARADIGM-HF was carefully designed to have the maximum chance of demonstrating that, and on that basis the FDA was surely right to approve it. Between those two extremes, though, it all comes down to price.

    Unfortunately (and one suspects it is no accident), PARADIGM-HF provides insufficient evidence to reliably estimate the true value of Entresto, making a quantitative assessment of its cost-effectiveness almost impossible.
    Interestingly, the Boston-based Institute for Clinical and Economic Review (ICER), a non-profit research organization, concluded last week that the list price of Entresto fairly reflected its clinical benefit, and could be considered “cost effective” (although they did note that with at least two million eligible patients, this would create a budget impact so high as to place excessive cost-burden on the healthcare system as a whole, and lead to material growth in health costs compared to national income). Importantly, though, ICER’s analysis modeled the benefit of Entresto using the PARADIGM-HF results – effectively ignoring the possibility that much of the benefit was illusory, due to the trial design.But without new data (none of which is on the horizon), it may be very difficult for clinicians and payers to resist the pressure to provide legions of heart failure patients with Entresto. A step-change in the treatment of heart failure it is not, but a blockbuster it will likely emerge nonetheless. The billion-dollar question (quite literally) for payers is how to stop clever clinical trial design by sponsors translating into vast unearned premiums being paid for unproven superiority in the future.
     
  10. anonymous

    anonymous Guest

    A stinker that will improve the quality of life for many.. another disgruntled, ex employee who didn't survive the cuts.. and.. whose opinion doesn't matter :)
     
  11. anonymous

    anonymous Guest

    $400 monthly degrades the quality of life especially for geriatrics , $30 a month worth of generics that perform the same job with 97-99% (if not 100%) of the same outcomes improves quality of life
    Payers aren't as gullible & in the tank as morons like you :cool:
     
  12. anonymous

    anonymous Guest

    You don't understand the science, that's sad. The NNT for the main end point is only 21. Incredibly significant…..
     
  13. anonymous

    anonymous Guest

    a bit too early to sour on this at this point.
     
  14. anonymous

    anonymous Guest

    Wait and see
     
  15. anonymous

    anonymous Guest

    Sad but true, the reps won't make much. It is an amazing drug, but the higher ups are treating the reps like they are 12 year olds and do not know what they are doing. The poor managers that are only pawns in the system, have no control and just follow. It is sad that with a drug like this people are not more excited.
     
  16. anonymous

    anonymous Guest

    what a shock no one's excited about the 20th diovan combo o_O
     
  17. anonymous

    anonymous Guest

    When does Entresto HCT hit the market
     
  18. anonymous

    anonymous Guest

    Right after the launch of EntrestAmlo
     
  19. anonymous

    anonymous Guest

    You mean Entrestaliskramloditensin HCT