The Deepening Debate Over Vaccines And Antimicrobial Resistance Involves IP 12/04/2017 by Tatum Anderson for Intellectual Property Watch 1 Comment Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to email this to a friend (Opens in new window)Click to print (Opens in new window)With the looming threat of antimicrobial resistance (AMR), there is growing pressure to use vaccines because they obviate the need to prescribe antibiotics in the first place. Take the pneumococcal conjugate vaccine (PCV), which protects against pneumococcal diseases – such as pneumonia, meningitis, and sepsis caused by the bacteria Streptococcus pneumoniae and is a leading cause of vaccine-preventable deaths among under-fives worldwide. Dr Abby Colson of the University of Strathclyde (Scotland) and AMR research group, the Center for Disease Dynamics, Economics and Policy (CDDEP), says that universal coverage of PCV could reduce antibiotic use for pneumococcal disease by 47 percent. “This really is a substantial decrease in antibiotics through the use of PCV,” she said. In fact, a global health security conference at held at London’s Chatham House last month focused on the value of such vaccines in containing the AMR threat. Today, there are two very effective vaccines that prevent pneumococcal diseases: Synflorix made by GSK and Prevnar by Pfizer. Together, these vaccines have averted child deaths by preventing pneumococcal disease and, importantly, the need for antibiotics. They have been rolled out to varying degrees in 139 countries, according to Baltimore’s International Vaccine Access Center (IVAC). The problem is that there are great big holes in the coverage of these vaccines. Fifteen years after pneumococcal conjugate vaccines’ first introduction globally in 2000, five of the highest pneumonia burden countries (India, Indonesia, Chad, China and Somalia) were still not using the vaccine in their routine immunization programs. (India is only just poised to begin roll-out this month, but it will take more than a year to roll out PCV nationwide). Experts such as Prof. Kate O’Brien, executive director of IVAC, say that’s largely down to the cost of the vaccines. Some of the poorest countries in the world receive heavily-subsidised vaccines through the Global Vaccine Alliance (Gavi). But less poor nations, classified as middle-income countries, cannot afford them either; they are not eligible for subsidies and do not have access to these lower prices. “These are countries that are not wealthy enough to invest in this vaccine themselves, and not poor enough to have the benefit of Gavi pricing and financial support,” she said. She reckons having more competition for PCV and other kinds of pneumococcal vaccines may help. “Having other efficacious pneumococcal vaccines on the market would be expected to influence price, which could tip the scale of affordability for some countries,” she said. Organisations from the Pan American Health Organization (PAHO) to UNICEF have tried to negotiate with the companies for lower prices. And the manufacturers have reduced their prices to varying degrees. GSK says it has delivered its vaccine at a deeply discounted price since 2010, but agreed to reduce it by a further 10 percent to Gavi-eligible countries this year to $3.05 USD per dose (three doses are required per child). In a statement, the company said: “We have expanded our volume commitments, pledging to deliver 720 million doses of the vaccine to 2024. Manufacturing at this scale has enabled us to identify incremental cost efficiencies. These have reached a threshold that we feel is meaningful and as a result we are able to offer this further $0.35 USD per dose tail price reduction to Gavi as of 2017 for Synflorix.” But at just under $10 per child, it’s not enough of a reduction, said Rohit Malpani, director of policy and advocacy at Médecins Sans Frontières (MSF, Doctors Without Borders), which has launched a campaign to fight for further price drops. “Our belief is that the cost of production and the profits that these companies have earned justify no more than five dollars for the full course of treatment,” he said. Enter Panacea Biotec, an Indian vaccine manufacturer that is developing its own pneumococcal vaccine, called Nucovac. That is a 10-valent, conjugate vaccine, which means it is essentially 10 vaccines in one, each able to combat a different strain of pneumococcus, and created using a process called conjugation. It’s also working on a 13/15-valent pneumococcal vaccine. Other manufacturers have been working on vaccines from China to Brazil; South Korea’s SK Chemicals and LG Life Sciences, Serum Institute of India (SII) and Indian pharmaceutical company Aurobindo Pharma – with its partner Tergene Biotech – are examples. Phase III trials are beginning or ongoing for some of these vaccines. The Phase-III trial of SII’s for instance, will start from May 2017 in Gambia and is being conducted and monitored by the NGO PATH. SII reckons its prices will be much cheaper – at $6 for all three doses – for public health programs and humanitarian organisations. Costs are high because the vaccine is so complex, said Dr Mark Alderson, director of the pneumococcal vaccine projects in the Center for Vaccine Innovation and Access at PATH, which has been working with SII. “It is probably the most complex vaccine from a manufacturing standpoint that has ever been produced. So that does keep the costs high compared with some of the other vaccines,” he said. (Indeed, that no other pneumococcal vaccines have been licensed in the 17 years since Prevnar was launched, is indicative of the complexity). That’s why early in the research program PATH and Serum Institute looked at how to best improve cost-efficiency. “It becomes very important if you are trying to sell the vaccine for as low as you possibly can. So we spent quite a lot of time trying to optimise the manufacturing processes to try and keep the vaccine cost as low as possible,” he said. In contrast, multinationals, planning to sell to markets such as the Europe and United States for a hundred dollars plus per dose, may not have focused on these issues as closely. “Efficiencies in the manufacturing process are not as critical. But they clearly are when your goal is to sell the vaccines at the lowest price possible for developing world markets,” he added. Fine-tuning the processes has also been key, for many of these vaccines, because of the potential for patent clashes. At least 106 patents on various aspects of pneumococcal vaccines were filed worldwide by 2015. Serum Institute conducted a detailed FTO analysis to work out how to reduce its risk of infringing patents and then developed alternative technologies that will not infringe on existing intellectual property. It licensed a technology from a company called Pfenex that should protect it. So says Dr Suresh Jadhav, executive director at SII. “With our 10-valent we will not run into IP problems and even if we are making higher valent vaccine, we will not have any problem as we are using the different technology for conjugation as well as different downstream process, which are not covered by the Pfizer patent,” he said. But others are challenging the patents head-on. Panacea challenged the GSK patent some years back. And in March last year, MSF filed a pre-grant opposition to a patent application, so-called 8081/DELNP/2007, in India too, in order to prevent Pfizer from patenting the method of conjugation within the vaccine. It wants to ensure that other manufacturers can produce more affordable versions of the vaccine, said MSF’s Malpani. “The method is too obvious to deserve a patent,” he said. “Our analysis is that this is a threat and could open companies to litigation.” (Panacea reportedly filed a pre-grant opposition to this application too but would not respond to requests for confirmation). Malpani said that an equivalent patent to the one opposed in India has already been revoked by the European Patent Office (EPO) and is currently being challenged in South Korea by SK Chemicals (which has now signed a partnership with French mega-vaccine player Sanofi). “We have some level of confidence given decision that was issued by the European Patent Office, and India has a very rigorous patent review process,” he said. Hearings have been held in the last year and the patent office’s decision is awaited. Despite numerous attempts, Pfizer did not respond to requests for comment on the application. But even if prices fell further or more pneumococcal vaccines were released tomorrow, it does not necessarily follow that all the children who require pneumococcal vaccines will get them. Many countries have poor health systems that cannot support rolling out so many vaccines – including the pneumococcal one. “A lot of work remains to assure that every child is able to receive all the vaccines they are due,” said IVAC’s O’Brien. “PCV that sits on the shelf does not save lives, only vaccine actually administered saves a life.” Image Credits: UNICEF Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to email this to a friend (Opens in new window)Click to print (Opens in new window) Related Tatum Anderson may be reached at email@example.com."The Deepening Debate Over Vaccines And Antimicrobial Resistance Involves IP" by Intellectual Property Watch is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.