David's New Book

Thursday, January 18, 2018

Antibiotic Price Perversion

I am hoping that readers with access to antibiotic usage data will be able to help here.

One of the legs upon which antimicrobial stewardship rests is to assure that the most efficacious and safe antibiotics are used in the appropriate dosage for the appropriate length of time in the context of any given infection. Based on numerous discussions with infectious diseases physicians, microbiologists and companies over the last 30 years, I believe that this approach to the use of antibiotics is undermined by the pricing within the antibiotics marketplace. 

One can only (with some exceptions) use antibiotics that are available within one’s institution or organization – that is – those that are on formulary. Formulary committees vary somewhat in how they make decisions as to which drugs to make available to physicians and patients, but most take into account clinical data, pharmacoeconomic data, microbiology and price.  They then try and make a value decision. Two factors work against new antibiotics. Generics like colistin are cheap. Most clinical data comes from non-inferiority trials. Pharmacoeconomics and microbiology may act to counter negative factors, but then there is the overall pharmacy budget.  In institutions, regions, and nations where the budget is tight, generics will be favored. Was linezolid favored by antimicrobial stewards for the treatment of MRSA pneumonia – even after it was shown to be superior to vancomycin? I don’t think so. (As I noted in a previous blog, there may have been a number of reasons for this).

One particular comment from a European expert sticks in my mind. We were discussing the issue of value-based pricing for antibiotics.  I was speculating on what the price for a new drug specific for Acinetobacter, for example, would have to be to provide a return on investment for its sponsor.  The discussion was based on a 2013 meeting held by Pew Charitable Trusts. When I mentioned prices ranging from $10,00 to $30,000 per course of therapy, this expert recoiled in disgust saying that in their country they would just continue to use colistin. This was in spite of the fact that at the Pew meeting, insurers had expressed a willingness to cover such costs depending on the data supporting the safety and efficacy of the antibiotic in question. I was shocked – but also na├»ve. This opinion was frequently stated by experts and pharmacists during market studies prior to the launch of Avycaz.

Recently, two antibiotics were shown to be superior to colistin both in terms of safety and efficacy – ceftazidime-avibactam and plazomicin. Of those, only Avycaz is currently marketed (plazo awaits regulatory approval).  A recent prospective observational study of caz-avi demonstrated a 9% mortality in the caz-avi group vs 32% in the colistin group – a 23% reduction in mortality when caz-avi was used as compared to colistin. Most infections treated were pneumonia or bloodstream infections. Renal failure was significantly more common the the colistin group and overall, there was a 64% chance that caz-avi treatment would lead to a better outcome compared to colistin.  A third new antibiotic, Vabomere (meropenem-vaborbactam),  has shown superiority to “best available therapy” (that often included colistin or polymyxin) in the treatment of infections caused by carbapenem-resistant pathogens.    It is now being marketed by Melinta.  

Given that cetazidime-avibactam has now been available globally for a period of time, and given good clinical practice and good stewardship, it should be replacing colistin/polymyxin in terms of prescription volume.  But sales data for 2016 do not yet bear this out.  Apparently, the cost of Avycaz in North America at around $8000 per course of therapy remains prohibitive. Vabomere is priced at about $5000-$10,000 or so per course of therapy as far as I can tell.  I have been unable to examine prescription volumes for these drugs to further substantiate my fear.  But I strongly suspect that the price perversion of the marketplace is leading to continuing use of inferior antibiotics when new but much more expensive antibiotics would be a better choice for patients.

I hope that one of you out there can help research this topic by examining prescription volumes (or by other methods) . . .

I think that all physicians and patients would agree that inferior therapy should not be used for potentially life-threatening infections. The question is – which price are we willing to pay – the price in dollars or the price in lives?