Heat-Stable Ritonavir Approved: Years of medical double standards and stranglehold by Abbott come to an end

Valérie Batselaere/MSF
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Years of medical double standards and stranglehold by Abbott come to an end

Paris/New York, February 12, 2010—Both the European Medicines Agency (EMEA) and the U.S. Food and Drug Administration have recently approved the long-awaited heat-stable 100mg tablet version of ritonavir, the antiretroviral booster drug produced by Abbott Laboratories.

The market authorisation of a heat-stable version of ritonavir as a separate pill finally ends both the stranglehold by Abbott on the treatment options available to people living with HIV/AIDS and the medical double standards the company has promoted by failing to prioritise the development of safer versions of its medicines.

Protease inhibitors (PIs) are the cornerstones of second-line AIDS therapy, as set out in World Health Organization (WHO) guidelines. PI-based regimens recommended in the guidelines include a booster drug, to be taken in conjunction with the PI, in order to make the regimen more effective. Ritonavir is still the only approved booster in existence.

Although Abbott has been marketing the heat-stable version of ritonavir since 2005, this has only been as a fixed-dose combination with its own protease inhibitor, lopinavir - not as a separate heat-stable pill. Until now, ‘standalone’ 100mg ritonavir was only available in a soft-gel formulation which requires refrigeration, making it extremely ill-suited for use in developing countries. This in turn severely restricted the choice of protease inhibitors for people on antiretroviral treatment, particularly in the developing world, as the use of all PIs other than Abbott’s own lopinavir came with refrigeration constraints.

By failing to move faster on creating a separate ritonavir tablet, the company therefore built a market advantage for its own PI lopinavir, and made the use of other life-saving protease inhibitors less practical.

Abbott’s delay extends to promoting medical double standards. The soft-gel version of ritonavir comes with more side effects and more dietary restrictions than the heat-stable version. In fact in 2007, the EMEA raised this as a public health concern with Abbott. The absence of a heat-stable ritonavir also restricted the possible use of second-line AIDS drugs for patients co-infected with tuberculosis.

As a result of Abbott’s inaction, many people living with HIV have therefore been deprived of additional, improved and vital treatment options.

Looking ahead, one particular area of need is the development of a heat-stable combination of atazanavir and ritonavir, one of the two PIs (with lopinavir/ritonavir) recommended by WHO for second-line treatment. A fixed-dose combination of atazanavir/ritonavir would in fact present considerable advantages over lopinavir/ritonavir, as it will reduce the pill burden from four to one pill a day.

Other PIs that require boosting with ritonavir are darunavir (which WHO indicates may form part of a future third-line antiretroviral therapy), and nearly all other PIs are more effective when used with a ritonavir booster. But to date, Abbott has not allowed manufacturers to produce any of these PIs in a fixed-dose combination with ritonavir.

It is hoped that generic manufacturers in developing countries will move forward with the development and registration of such boosted heat-stable PIs as fixed-dose combinations. Where there are potential patent barriers that prevent them from doing so, use should be made of safeguards in patent laws to ensure these are overcome.

MSF calls on Abbott to:

• Register heat-stable ritonavir tablet widely in developing countries.

• Ensure that the price is affordable to patients in all developing countries (Abbott’s discounted price of US$83 per person per year for the heat-stable and soft-gel versions of ritonavir is only available for the absolute poorest countries).

• Develop a more adapted heat-stable paediatric formulation of lopinavir/ritonavir (such as soluble granules or sprinkles) for young children who can not swallow the existing tablet.

• Facilitate access to more affordable versions of ritonavir and fixed-dose combinations containing ritonavir by putting the patents on ritonavir into the Patent Pool for HIV medicines currently being set up by UNITAID.