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

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?"

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