Greg Perry, Executive Director of the Medicines Patent Pool, told delegates at the World Hepatitis Summit in Glasgow last week that the organisation was considering how it could act to speed up and expand access to direct-acting antivirals for lower- and middle-income countries, where around 85% of people with hepatitis C are estimated to live.
The Medicines Patent Pool was established with the support of UNITAID, the international drug and diagnostics purchase fund for HIV, tuberculosis and malaria, to negotiate voluntary licensing agreements with pharmaceutical companies that would allow widespread access to low-cost antiretroviral drugs for HIV treatment. The Medicines Patent Pool was also designed as a mechanism to overcome barriers to the development of fixed-dose drug combinations of products from more than one manufacturer, for efficient delivery of treatment in lower- and middle-income countries.
Since its launch in 2010, the Medicines Patent Pool has negotiated voluntary licensing agreements with all the major pharmaceutical companies that allow some or all of their antiretroviral products to be copied by generic manufacturers for sale at greatly reduced prices in lower- and middle-income countries.
Some of the most important drugs used in HIV treatment are now covered by Medicines Patent Pool agreements, although the geographical scope of the agreements varies between products.
Now the Medicines Patent Pool is weighing whether it can make a similar difference in the field of viral hepatitis, where access to new antiviral drugs is very limited outside higher-income countries.
The Medicines Patent Pool’s first priority is to negotiate voluntary licensing agreements that would allow the development of pan-genotypic combinations of direct-acting antivirals. Pan-genotypic drug combinations should be equally active against all genotypes of hepatitis C. Although many advocates argue that pan-genotypic combinations are needed in order to simplify treatment by dispensing with the need for genotype testing, a greater advantage to a pan-genotypic combination would be efficacy against all the genotypes present in lower- and middle-income countries, allowing a larger proportion of the population with hepatitis C infection to benefit from lower-cost treatment. Whereas genotype 1 predominates in the high-value markets of Europe and North America, the mixture of genotypes is far more varied in Asia and Africa. Whereas all direct-acting antiviral combinations are active against genotype 1, some are much less potent when used to treat genotype 3. Having one regimen that suits all patients would vastly simplify treatment by removing the need for a mosaic of national guidelines to cater for local variations in the genotype mix, and would overcome delays in registration of multiple products needed to treat different genotypes.
Dr Isabelle Andrieux-Meyer of Médecins sans Frontières urged the Medicines Patent Pool to prioritise daclatasvir in order to achieve a pan-genotypic combination with sofosbuvir – and to forestall a Gilead monopoly in pan-genotypic treatment.
“Our number one priority is to open up negotiations with Bristol-Myers Squibb [on daclatasvir]. We think they have the most interesting product,” Greg Perry told delegates. Bristol-Myers Squibb has not yet published voluntary licensing proposals for daclatasvir (Daklinza).
Approximately 85% of people with hepatitis C live in lower-income or middle-income countries, Homi Hazawi of the Center for Disease Analysis said, but a major challenge facing all efforts to reduce the price of hepatitis C treatment lies in the fact that a large number of these people live in countries such as China, Brazil and Russia which may not be covered by voluntary licensing deals. A review by the Center for Disease Analysis suggests that 23 to 29% of people with hepatitis C live in upper middle-income countries, and 43 to 49% in lower middle-income countries.
The only existing voluntary licensing arrangements for hepatitis C cover Gilead’s products Sovaldi (sofosbuvir) and Harvoni (sofosbuvir/ledipasvir). Voluntary licensing to 11 Indian generic manafacturers allows those companies to market versions of the Gilead products in 101 lower- and lower middle-income countries, and to combine the agents with other products not owned by Gilead. Strict anti-diversion measures designed to prevent the drugs being sold in markets not covered by the licence have also been agreed, but these terms have been strongly criticised by Médecins sans Frontières for their potential to harm patient confidentiality and autonomy. Advocates would like to see less onerous terms and greater coverage of middle-income countries in future licenses.
Greg Perry believes that the Medicines Patent Pool can deliver better deals through experience and persistence, but warned delegates, “We have to be realistic. I cannot promise to deliver China or Brazil.”
Some advocates, including Initiative for Medicines, Access and Knowledge (I-MAK), argue that compulsory licensing by governments will be necessary in order to achieve access for middle-income countries, but a lawyer with expertise in compulsory licensing told delegates that he was sceptical regarding its potential to achieve widespread access to low-cost drugs.
“The best we can do is win a couple of cases once in a while on a couple of products,” said James Love of Knowledge Ecology International, which has provided legal advice on compulsory licensing of HIV drugs for over a decade.
Brook Baker of Northeastern University, Boston, warned that due to the lack of donor funding for hepatitis treatment in lower- and lower middle-income countries, it will be difficult to create the volume of demand needed for large reductions in the price of generic versions of direct-acting antivirals.
“If the volume is not there the market is not very interesting for generic companies,” said Peter Bayer of the World Health Organization. Unless governments set up programmes to test and treat for hepatitis C, generics will remain expensive drugs only available through private pharmacies, he warned.
For more information on the World Hepatitis Summit visit www.worldhepatitissummit.com