31 January 2012
On December 19 2011, Johnson & Johnson (J&J) announced its decision not to enter into negotiations with the Medicines Patent Pool at this time. In media statements following the announcement, J&J made inaccurate statements about the negative public health impact the work of the Pool may have. This note responds to those allegations and presents the case for J&J to license to the Pool.
Limiting the Development of Inappropriate Formulations
In a recent article in the Financial Times, J&J’s Worldwide Chairman for Pharmaceuticals expressed concern that the Pool’s work could lead to the mixing and matching of medicines that would cause a surge in patient resistance, a statement repeated in other media.[a]
The statement unfortunately raised concerns about one of the main aims of the Pool: the development of needed new formulations for use in developing countries, especially fixed-dose combinations (two or more medicines combined into one pill).
The Pool promotes the development of appropriate and quality assured fixed-dose combinations (FDCs) that meet treatment needs in developing countries, which is very different from the indiscriminate mixing and matching of medicines. Promoting FDCs is a central part of the Pool’s mandate as established by UNITAID[b] and responds to the need for more simplified, less toxic drug regimens as recommended by the World Health Organization (WHO).[c]
The use of FDCs in resource-limited settings promotes the use of the best and safest combinations, by reducing treatment error, selective non-compliance and the erratic use of inappropriate combinations or single components. FDCs also simplify stock management and supply and improve adherence to treatment.Rather than increasing resistance, the use of FDCs with assured quality enhances treatment effectiveness, reduces the use of inappropriate combinations and therefore reduces the chances of patient resistance.[d] The advantages of FDCs for the treatment of HIV have been widely recognised by the public health community, including by the WHO.[e]
Through its work, the Pool promotes the development of appropriate WHO-recommended FDCs, that might otherwise not be developed or remain inaccessible due to price.
In 2009 and 2011, the Pool, UNITAID and the WHO jointly submitted a list of missing essential medicines and FDCs needed for the treatment of HIV in resource-limited settings to the WHO expert committee on essential medicines. The document was endorsed by the Committee and a wide range of international partners and represented a first step in WHO’s and UNAIDS’ efforts to optimise treatment regimens for HIV, under the Treatment 2.0 initiative.[f]
Pool licences are structured, in discussion with patent holders, to ensure that only formulations and combinations that meet treatment needs in developing countries and that are endorsed by the scientific community are developed.
Products developed under Pool licences must meet the quality standards of the WHO Prequalification Program or those of internationally recognised stringent regulatory authorities.[g] The WHO Prequalification Program only approves medicines, including FDCs, which have previously been identified by the WHO HIV experts as the best therapeutic options.[h] This further ensures that inappropriate combinations or formulations are not approved. Details on the Pool’s collaboration with the WHO Prequalification Program can be found in a joint document available on the WHO website.[i]
The Importance of Johnson & Johnson Products in the Pool
In its recent statements on the Pool, J&J cited low “clinical demand” for its products in resource-limited settings as a reason for not entering into negotiations with the Pool yet. But this decision risks delaying access to these important medicines for a long time into the future, even after demand for them begins to rise.
There are currently no generic producers for J&J products darunavir and etravirine, both currently recommended by the WHO for third-line treatment.[j] The prices for these products make them unaffordable in most developing countries.
Data from the Global Price Reporting Mechanism indicates prices of over USD 10,000 per patient per year for darunavir in Georgia, over USD 7,000 in Nicaragua, and over USD 1,000 in Rwanda. Similar prices have been paid for etravirine.[k] And these prices represent only one component in a treatment regimen that often contains several drugs.
Through the Pool mechanism, which brings generic companies into the market, these prices can be brought down to levels the global HIV treatment community can bear.
Early treatment regimens based entirely on generics now cost as little as USD 130 for a complete first-line regimen and approximately USD 450 for a second-line regimen.[l] These costs represent a 99% reduction in price due to competition among generic companies.
Given the time lag of at least 3 years for the development of generic medicines and combinations, and their regulatory approval, waiting further to enable generic product development, production and sale of these products in developing countries will likely delay access for many years to come, at a time when the clinical demand for these products may increase. The same would apply to promising FDCs or co-blisters that may either not see the light of day for several years or are blocked in countries that need them.
Current agreements by J&J for darunavir and etravirine are limited to one or two companies per product, very limited geographical scope and focus primarily on registration, packaging and distribution.[m] There are patents on these products in many developing countries, so robust generic competition will not be possible under such circumstances. Without generic competition, prices are likely to remain high and access will be denied to most patients in need.[n]
The US National Institutes of Health (NIH) carried out research on darunavir, and patents related to darunavir owned by the US government have been licensed to the Pool.[o] However, licences are also required from J&J to enable generic production and sale of darunavir where there are patents.
In the case of rilpivirine, a product approved in the US and Europe that holds promise in resource-limited settings,[p] J&J has reached bilateral agreements with five select licensees. The terms and conditions of those agreements, however, have not been disclosed and concerns remain on how restrictive they may be and whether critical public health safeguards have been included. The product has been widely patented in developing countries, including in countries that are key suppliers of generic antiretrovirals, and there are likely to be constraints to generic competition for the single compound and its combinations with other antiretrovirals, including its combination with tenofovir and 3TC or FTC.
The Pool, therefore, invites J&J to reconsider its recent decision and enter into negotiations with the Pool, so that access to its products no longer remain limited and unaffordable to people in need in developing countries.
The Pool was created as a public-health-oriented voluntary licensing mechanism to enhance access to HIV medicines and promote the development of needed formulations. It has been endorsed by the international community at the UN General Assembly and the World Health Assembly. It provides the ideal conduit for ensuring greater access to J&J’s products in a responsible, access-friendly and transparent manner. The Pool calls on J&J to recognise this and reiterates its invitation to begin formal negotiations.
[g] The Pool’s quality assurance requirements are in line with the standards used by the Global Fund to Fight HIV, Tuberculosis and Malaria, PEPFAR and the UN agencies that are involved in the procurement of antiretrovirals.
[m] See: http://www.tibotec.com/bgdisplay.jhtml?itemname=dw_leftblock1 (accessed on 19/01/2012)
[n] Data from the Pool’s patent status database indicates that patents relating to darunavir and etravirine may block generic competition in a large number of developing countries. See: http://www.medicinespatentpool.org/LICENSING/Patent-Status-of-ARVs