By: Brook K. Baker, Senior Policy Analyst, Health GAP
AbbVie and the Medicines Patent Pool (MPP) have negotiated a royalty-free licensing and sublicensing agreement on a priority hepatitis C direct-acting antiviral, glecaprevir and pibrentasvir (G/P). This G/P combo is recommended by the World Health Organization (WHO) as a pan-genotypic adult first-line regimen with ongoing Phase 3 trials for adolescents and children. G/P has a high resistance barrier and the shortest treatment duration of any HCV regimen to date.
The main drawback of the MPP-AbbVie license is its limited geographic scope—particularly its exclusion of India, a high burden country with a significant population of people living with HCV. Not only are there fewer countries and territories included in the license (95 and 4 respectively, Table 1) than in previous licenses for direct-acting antivirals (DAAs) for HCV, but the percentage of the global population living with HCV covered—47.5%—is lower than Gilead’s bilateral license for sofosbuvir (105 territories, 62.3% coverage) and Bristol-Myers Squibb’s license for daclatasvir (112 territories, 54.3% coverage). Consistent with previous licenses, AbbVie has prioritized exclusion of so-called “emerging markets” and upper-middle-income markets, in order to maximize profit in those markets.
This will have grave health consequences now for people suffering with untreated HCV in those countries, and in the future. Excluding countries with more capacity to finance reasonably priced HCV elimination strategies shrinks the overall market for generic G/P, reduces economies-of-scale for generic producers, and thus undermines treatment and elimination strategies in licensed territories as well. As another negative, the license restricts production to companies located within the licensed geographies plus India (as a manufacturing country only).
The patent situation in India and other excluded territories is important. There are five relevant patents filed on G, P, and G/P in India, one of which involving pibrentasvir is being opposed by I-MAK. A first examination report on that application, since amended, detailed multiple grounds for denying a patent. If oppositions are expanded to the other four applications, if they are all successful, and if AbbVie does not unduly extend evaluation of its patent applications via substitutions, selection, amended or protracted appeals, then Indian generic companies would eventually be permitted to supply India and other excluded territories where no granted patent is in force. Thus, the MPP licenses accomplish some “wholesale” work in facilitating generic entry and competition in 99 countries and territories. Moreover, complementary oppositions could eventually open up opportunities in some excluded territories as well, since the license allows supply to countries and territories if no granted patent will be infringed. Unfortunately, G/P appears to be very widely patented in LMICs, with 30 out of 32 extra-territorial LMICs in the MedsPAL database reporting granted and pending patents (Table 2) [source]. On the plus side, there is some possibility that the MPP, countries, and activists will be able to convince AbbVie to expand the licensed territory, including in India, while generic licensees develop and register the licensed product. AbbVie should clearly do so, but even if it does not expand the licensed territory, countries where patents are in effect still have the option to issue compulsory licenses and to be lawfully supplied by generic sublicensees.
No one should have to suffer from untreated HCV—a virus with very good prognosis for cure but where gross inequities are keeping medicines out of reach. Countries should urgently deploy all available mechanisms, including compulsory licensing, in order to obtain low cost, generic versions of G/P.
Table 1: Countries and Territories Included in the License
Afghanistan, Angola, Antigua and Barbuda, Bangladesh, Belize, Benin, Bhutan, Bolivia, Botswana, Burkina Faso, Burundi, Cambodia, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Cook Island, Côte d’Ivoire, Democratic Republic of the Congo, Djibouti, Dominica, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Fiji, Gabon, Gambia, Georgia, Ghana, Grenada, Guadeloupe, Guinea, Guinea-Bissau, Guyana, Haiti, Indonesia, Jordan, Kenya, Kiribati, Laos, Lesotho, Liberia, Libya, Madagascar, Malawi, Maldives, Mali, Marshall Islands, Mauritania, Mauritius, Micronesia, Morocco, Mozambique, Myanmar, Namibia, Nauru, Nepal, Niger, Nigeria, Niue, Pakistan, Palau, Papua New Guinea, Philippines, Rep., Reunion Islands, Rwanda, Saba, Saint Eustatius, Saint Kitts and Nevis, Saint Lucia, Saint Vincent & the Grenadines, Samoa, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, Solomon Islands, Somalia, South Africa, South Sudan, Sri Lanka, Suriname, Swaziland, Tanzania, Timor-Leste, Togo, Tunisia, Turkmenistan, Tuvalu, Uganda, Vanuatu, Vietnam, West Bank & Gaza, Yemen, Zambia, Zimbabwe
Countries in bold have filed or granted patents
Table 2: LMICs with Granted or Pending Patents Excluded from the License
(MedsPAL Nov. 13, 2018)
Albania, Armenia, Azerbaijan, Belarus, Bosnia & Herzegovina, Brazil, China, Colombia, Costa Rica, Dominican Republic, Ecuador, Guatemala, India, Kazakhstan, Kyrgyz Republic, Macedonia, Malaysia, Mexico, Moldova, Mongolia, Montenegro, Paraguay, Peru, Russia, Serbia, Tajikistan, Thailand, Turkey, Ukraine, Venezuela
*Nicaragua and El Salvador listed at having no relevant patent filed