Monday, 17 December 2012

Monoclonal antibodies: magic bullets with a hefty price tag

#MSBlog: How much is too expensive? The monoclonal antibody revolution!

Allen Shaughnessy. Monoclonal antibodies: magic bullets with a hefty price tag. BMJ 2012;345:e8346.

Excerpts:

... The pharmaceutical industry just doesn’t feel the love these days. Mistrust abounds among the general public as well as within the medical industry. It’s no surprise, then, that eyebrows raise and fingers point when a company withdraws an effective drug from the market shortly after proof is published of its benefit in a completely new treatment arena. What is it up to? ...

... Alemtuzumab is a monoclonal antibody marketed to treat chronic lymphocytic leukaemia. It has also been used, off-label, for multiple sclerosis, and last month two phase III studies were published showing its efficacy and superiority over interferon beta-1a. The US Food and Drug Administration and the European Medicines Agency are considering approval for this indication. ...

... By now many patients with multiple sclerosis should be taking the drug, even though it hasn’t yet been sanctioned for this use by regulatory agencies. But Genzyme, a Sanofi company, withdrew it from the market two months before these studies were published. Some predict that once it is approved for multiple sclerosis alemtuzumab will be re-released under a new brand name (and at a much lower dose than that used for leukaemia), this time at a much higher cost. ...

... From a business perspective, this move makes sense. The cost of Campath, the brand name for the leukaemia version, was about $60 000 (£37 000; $46 000) a year. Lowering the dose to that used to treat multiple sclerosis would have reduced the price to $6000 a year. ....

... This would have been a bargain basement price for immunomodulator treatment of multiple sclerosis. Natalizumab, another monoclonal antibody used for multiple sclerosis, is about $55 000 a year. ...

... Perhaps the manufacturer is taking its cue from Genentech, a subsidiary of Roche Pharmaceuticals, which sells bevacizumab for colon and other cancers and ranibizumab to treat patients with age related macular degeneration. ...

... Although ranibizumab has theoretical advantages, and bevacizumab is not licensed for macular generation, clinicians around the world use bevacizumab rather than ranibizumab for the eye disorder because it is much cheaper. The cost differential was so striking that one primary care trust authorised the off-label use of bevacizumab rather than pay for the higher priced option, reversing its stance only after the company offered price concessions. ...

... Yet it seems inherently unfair to take a product, lower the dose, and inflate the cost several orders of magnitude. The uniqueness of monoclonal antibodies and the complexity of their development and production are touted as reasons why these products are so expensive. But is it really justified? ...

... Multiple sclerosis occurs when T and B lymphocytes mistakenly attack the myelinated axons in the central nervous system, destroying the myelin and axon to varying degrees. Alemtuzumab targets T and B lymphocytes while sparing other immune system elements. The antibody binds to the CD52 protein found on the surface of mature lymphocytes but not the stem cells that produce them. After treatment, these CD52 lymphocytes, now tagged with the antibody, are destroyed by the immune system. Depletion of these lymphocytes is pronounced and long lasting, with a median recovery time to normal levels of 35 months. ...

... Two recently published phase III studies have shown that alemtuzumab is effective in patients with relapsing-remitting multiple sclerosis. The studies, called Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS I and II), enrolled previously untreated patients with low disability levels (CARE-MS I) and patients with a history of disease activity despite immunomodulator treatment (CARE-MS II). Alemtuzumab was more effective than interferon beta-1a in preventing relapses over the two years of study, producing a 54.9% improvement in previously untreated patients and 49.4% improvement in patients who had had treatment. In patients with more advanced disease, alemtuzumab also decreased the number of patients experiencing sustained accumulation of disability (hazard ratio 0.58, 95% confidence interval 0.38 to 0.87). ...

... Why so expensive?

The top 12 biological products in the United States brought in combined revenue in 2010 of $30bn. By 2014, sales are expected to increase to $166bn, comprising about 30% of the branded prescription drug market....

... The average cost for the top nine biologicals is more than $200 000 a year in the US. The most expensive drug in the world is eculizumab, used to treat the extremely rare paroxysmal nocturnal haemoglobinuria, which affects about 5000 patients in the US and 1000 in the UK, costing a whopping $409 500 a year for the average patient. ...

... End result versus perceived value?

Had alemtuzumab not been previously available for the treatment of cancer at a lower price, there would have been no expectation regarding its cost, other than it would be in the range of existing multiple sclerosis treatments. ...
... How do we decide what a product is worth? It is a human perversity that we are willing to pay a lot for something—until we know the cost of production. Then, we resent paying more, despite the fact that the product still is useful to us. ...

.... Monoclonal antibodies in numbers
  • $30bn: the combined revenue from the top 12 biological products in the United States in 2010
  • 453%: expected increase in US sales of the above top 12 from 2010 to 2014. It will bring annual revenues to $166bn, comprising about 30% of the branded prescription drug market
  • $200 000: average cost of treating a patient for a year with one of the top nine biologicals in the US
  • $409 500: average cost per year for the average patient on the most expensive drug in the world, eculizumab, used to treat paroxysmal nocturnal haemoglobinuria
  • $2: average raw material cost per gram of product produced

Monoclonal antibodies targeting a cell surface antigen.

"It looks as if the BMJ is on a mission to put Big Pharma to task about its monoclonal antibody pricing strategy. What the BMJ need to remember is that Pharma are business and have to make profits. The profits are necessary to pay their shareholders dividends; most people living in the UK who have a private pension are relying on Pharma paying for some of their retirement costs. Pharma profits are taxed and help governments balance the books; in the UK this will help with deficit reduction. The problem with relying on Pharma profits in the UK is that a large number of Pharma companies have, or are, disinvesting from the UK. Are you surprised? More importantly pharma profits pay for R&D and the future drug pipeline. For example, Genzyme have launched a development programme targeting progressive MS and symptomatic therapies. This is something they should be congratulated for."

"Its time to stop bashing Pharma; we don't want to throw the baby out with the bath water. Or have we already? It is never too late?"

12 comments:

  1. The medical system (doctors, medical journals, the NHS, etc) exists only to improve public health and serve the needs of patients.

    Protection of pharma profits, pharma taxes, or pension funds is not its job

    ReplyDelete
    Replies
    1. You are obviously not an economist. Do you want UK PLC to be like Cuba? Cuba has an NHS.

      Delete
    2. I'm not an economist, I'm not even from the UK.

      Look at the UK Dept of Health website http://www.dh.gov.uk/health/about-us/

      Their responsibilities do not include making sure UK pharma pays high taxes to the government and high dividends to pension funds. No reason why Prof G and the BMJ should be concerned about it.

      Different parts of the government can have different interests and views. Trade/industry and finance ministries around the world must have protested when governments started cracking down on smoking. Tobacco companies also pay lots of tax and dividend.

      Delete
    3. I think neurologists and medics need to take a broader view of things; we are not immune to thinking. As I have said before all complex systems have feedback loops and the drug industry is no exception. So we need regulators to keep the lid on pricing, which is what NICE and other healthcare providers are doing.

      What I am more concerned about is punitive action that results in lack of investment in R&D; the driver of innovation. We, the MS community, need it more than ever. The unmet need in MS is massive and without investment we are never going to get on top of progressive MS and all the symptomatic problems MSers have. Unfortunately, drug development doesn't happen outside of Pharma, which is why we need to stop the Pharma-bashing and start treating them as partners in our fight against MS.

      The BPA that we have launched, is not an anti-pharma initiative is to deal with the issue of repurposing of off-patent drugs. There is no incentive at present to license off-patent drugs. We need to change this.

      http://multiple-sclerosis-research.blogspot.com.es/2012/11/the-bigpharma-alternative.html

      Delete
    4. I think neuros should put patient interests over anything else. At times this can mean working with pharma, and at times it can require them to go against pharma interests.

      Delete
  2. This blog also has an opinion on the same monoclonal antibodies article

    http://blogs.bmj.com/bmj/2012/12/17/richard-lehmans-journal-review-17-december-2012/

    Says:
    "The author is from Tufts University, Boston, Mass. ... He is keen to protect the manufacturers from any accusations of profiteering and never drops any hint that there could possibly be a different business model for developing and marketing these drugs. I think it’s time that healthcare payers in all developed countries got real about the future, and joined together to set up a different way of doing things. To my mind, it can only lie in collaborative global not-for-profit development of targeted treatments: otherwise all medical innovation is going to become unaffordable, and absolutely unavailable to those who most need it."

    ReplyDelete
  3. Wow, Prof G. To read your post reminds me of some Secretary of Foreign Affairs paraded in front of the world media attempting to justify the abhorrent actions of some tyrannical despot he’s working for. For you to whitewash Big Pharmas sickening need to generate huge profits as means of contributing to the public purse is both worrying and shameful. The notion that by driving up prices they are bettering everyone’s living standards is ignorance of the highest order. The UK deficit remains astronomically high and over 2.5 million pensioners living in Britain are, according to official statistics, living below the poverty line. Big Pharma is not working to alleviate the world of ill health, merely, they are using disease as a ploy to maximise greed. They have cunningly founded a way to make money out of treating disease without curing it. The money is in the medicine, not in a cure. Now that it is apparent that diseases like MS do not lend themselves to a one-all treatment for everyone, and will require a more bespoke approach, Big Pharma is naturally less interested.

    Do not pretend that you have not also made money by working in cahoots with Big Pharma because you have in a consultancy capacity. How you can defend the actions of pharmaceutical corporations when they sue the NHS for utilising alternative medicines is beyond me. If Big Pharma is a business then so is the NHS. If Pharma is answerable to its shareholders then the NHS is answerable to its tax payers.

    If Big Pharma will withdraw from research and development, then fine. It’s not as if these drugs peddled out by Big Pharma in the name of MS tackle the fundamental causes of the disease. 80% of MSers will go on to develop progression and disabilities despite taking DMTs to reduce relapses. That is a fact. All that DMTs offer is symptomatic relief. Even the new emerging DMTs can’t guarantee they’ll fix damage. Everyone living with MS right now is on a destructive trajectory from which there is no coming back. That’s a fact. No matter how much they pump themselves full of pointless toxic drugs will alter that.

    We as a culture need to turn our backs on DMTs and live with the disease. Whatever the outcome, just accept it. These drugs will not get rid of your MS. The government must never capitulate to the greed of Big Pharma and ought to banish DMTs being paid for by tax payers.

    In truth, NICE will never greenlight these emerging DMTs to be used by all MSers, especially not those in the early phases of disease activity. If MSers want early and aggressive treatment then they ought to pay for it from their own pockets, not from mine. MS and all its complication are here to stay. Live with it and accept with absolute simplicity all that MS entails. As long as Big Pharma is driven by sociopathic intents, you will never be cured.

    ReplyDelete
  4. Dr Dre,
    Your standpoint is a recipe for hopelessness and no progress. Though some might share your view, I imagine that the majority don't.

    ReplyDelete
  5. R&D and innovation in Pharma industry is a bad joke if you consider the amount of money spent on marketing.

    You have many times repeated in this blog that the emergence of a new drug takes enormous amount of money that only Pharma have and are willing to spent. It sounds logical at first, but if you think about it you start to feel the smell of greediness. Because:

    a) Pharma companies have become artificially gigantic by producing thousands products of minimal or zero efficacy, exploiting the dogma that a drug can be made against any condition, and that minimal efficacies are acceptable in the absence of true therapy. Yet it only takes a 12 year old to understand that a substance that "helps" less than half of its consumers is probably rubbish.

    b) In order to get those crappy substances licensed Pharma companies have to devise metrics that can be manipulated in the course of a clinical trial, but are otherwise irrelevant to the treated condition (relapses and MRI lesions in MS). This kind of manipulation can only be hidden in large, costly trials, preferably with high cost lab tests involved. So, the astronomical cost of drug creation and licensing is absolutely necessary in order to manufacture the consent needed to sell virtually ineffective compounds. It is also the Darwinian way of keeping the process in the hands of few, powerful Pharma companies and leaving all competitors aside.

    ReplyDelete
    Replies
    1. It is what it is and we have to work with them because there is no alternative (and never likely to be).
      I'm the last person to be a cheerleader for pharma but as prof G explains we have to keep things in perspective.

      Delete
  6. Why do they need such a hefty price tag? It's not as if anyone can do a 'me too' monoclonal antibody unlike ordinary pharmaceuticals. They'd have to go through trials again, therefore, pharma producing mono antibodies have a monopoly. Unless they are trying to protect the other drugs they produce?

    ReplyDelete

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