Research universities have “considerable untapped influence” that they should use to make biomedical innovations available and affordable for developing nations, according to a commentary published last week in the Journal of the American Medical Association.
The commentary suggests that universities should modify their licensing strategies to include terms that ensure low-cost access to medicines and encourage generic competition in poor countries. In addition, according to one of the article’s authors, universities are obligated to exert their influence beyond licensing agreements by publicly pressuring licensees into socially responsible pricing and forming alliances with other schools to develop and execute pro-access policies.
The article is one of several recent signs of an increasing awareness of the role that universities play in expanding global access to biomedical innovations developed with federally funded research. It comes in the wake of a conference and controversial op-ed article from student movement Universities Allied for Essential Medicines, and a “socially responsible” vaccine licensing agreement between Harvard University and China’s Morningside Group.
It also follows a white paper published earlier this year by tech-transfer officials at the University of California at Berkeley and Stanford on socially responsible licensing (see BTW, 3/19/2007).
Dave Chokshi, a medical student at the University of Pennsylvania School of Medicine, and Rahul Rajkumar, a physician at Brigham and Women’s Hospital, co-authored the commentary, which was published last week in a special issue of JAMA focusing on poverty and human development.
According to the authors, research universities play a critical role in influencing the cost and availability of medical innovations in developing countries “by virtue of their upstream contribution to the drug development pipeline” – estimated at $19.6 billion in 2002 for the US alone.
In addition, the authors provide the example of several currently marketed HIV drugs whose patent rights are held by universities. These include stavudine (Yale University); abacavir (University of Minnesota); lamivudine and emtricitabine (Emory University); and enfuvirtide (Duke University). Overall, the authors write, university patents are associated with 10 of the 30 HIV drugs approved by the US Food and Drug Administration between 1987 and 2007.
Chokshi and Rajkumar also point out the necessity to expand access to treatments for chronic illnesses such as diabetes and cardiovascular disease, noting that of the 35 million worldwide deaths from chronic disease in 2005, 80 percent occurred in low- and middle-income countries.
When university-owned intellectual property is necessary for the development of a potential health-related product such as a drug, vaccine, or diagnostic test, the authors write, universities could craft exclusive licensing agreements that ensure low-cost access to the product in developing nations.
One way to do this would be to engender generic competition in poor countries by adopting, for example, the “equitable access license” developed by UAEM, which allows multiple producers in low- and middle-income countries to manufacture and sell a version of a product free of IP constraints, according to Chokshi and Rajkumar.
In situations where such a licensing provision is not feasible because reverse engineering of the product is difficult – such as with a vaccine or biologic medicine – universities should adopt a “global access strategy” that would require the licensee to sublicense IP at a low cost, make its own product available at a low cost, or participate in patent pools with other companies or institutions to better enable cross-licensing agreements that would increase access to the product in developing nations, the authors write.
“What we were hoping to inject into this debate is some level of specificity, because unfortunately it is all too easy for university decision-makers to agree to this general principle of what should be done, but when the rubber meets the road, it doesn’t make a difference if all that is talked about is this high-level principle,” Chokshi told BTW last week. “We’re trying to take it to the next level to develop specific policies that could be implemented that actually bring that principle to bear.”
The full commentary can be seen here.
The commentary echoes public policy changes suggested by UAEM, a group that both Chokshi and Rajkumar have been involved with in the past that has been particularly active in promoting its agenda in recent weeks.
UAEM is a university student movement that grew out of a successful 2001 campaign by students at Yale University to pressure Yale into expanding third-world access to stavudine, Robynn Sturm, a graduate student at Yale Law School and member of UAEM’s board of directors, told BTW.
Since that time, the movement has evolved primarily into a graduate student organization with the backing of numerous university faculty members. UAEM just completed its first fund-raising campaign, assembled an advisory board and board of directors, and hired its first permanent staff.
Late last month, UAEM held its fourth annual conference on Harvard’s campus. Chokshi and Rajkumar were among the speakers at the conference, which, according to UAEM, attracted more than 300 students from the US, Canada, and the UK.
Following the conference, UAEM board president Rachel Kiddell-Monroe and executive director Ethan Guillen co-authored an op-ed piece that was published in the Boston Globe. In the piece, UAEM called on US research universities to join the UAEM movement, and urged current member institutions to “turn the promises of their commitment from words into action.”
In particular, the article criticized the University of Wisconsin and its tech-transfer operation, Wisconsin Alumni Research Foundation, for it’s involvement with Abbott’s kidney medication Zemplar, which was originally developed by UW researchers.
In the fall of 2006, Abbott lowered the price of its AIDS drug Kaletra in Thailand in response to a request from the Thai government. However, Thailand officials, feeling the price reduction was not enough, instituted their own compulsory drug license allowing generic versions of Kaletra to be manufactured and sold in the country without regard to Abbott’s patents on the medicine.
Abbott responded by withdrawing several of its new drugs, including Zemplar, from entry into the Thai market. According to UAEM, WARF essentially ignored the requests of a group of concerned UW students to urge Abbott to reintroduce Zemplar into Thailand. In the op-ed piece, Kiddell-Monroe and Guillen wrote that UW “must demand that Abbott Industries reinstates Zemplar on the Thai market, along with the other essential medicines.”
Sturm told BTW that UAEM ideally would like to see universities include in every single license a provision that would enable any qualified supplier to provide generic versions of essential medicines to poor countries, even before the patents expire or lose their exclusivity.
“The pharmaceutical company would maintain full and exclusive rights within developed countries,” she said. “But in those spaces where they’re not making any money anyway, because people can’t afford brand-name drugs, they would allow for other companies to step in and do it at a much lower price.”
In an e-mail to BTW regarding UAEM’s article, WARF communications director Janet Kelly wrote: “WARF's license to Abbott Laboratories for the compounds used to manufacture Zemplar dates back to 1998. It is an exclusive license and legally binding contract for both parties. Abbott has met the terms of our licensing agreement. It is not feasible for WARF to seek changes to existing agreements with customers in good standing.”
Kelly added that Abbott has been an “excellent partner” for WARF with “proven ability to successfully develop and commercialize new drug discoveries that benefit patients around the world.”
But Chokshi said that WARF – and other universities that have espoused similar comments – are guilty of a “unidimensional view” of the influence that universities can have on the access to medicines in poor countries.
“There are various forms of leverage. It doesn’t have to do solely with legal or licensing interventions,” Chokshi said. “It can be anything from making an informal phone call and trying to do the right thing with respect to a technology developed by a scientist at your school, to taking a more publicly confrontational stance if the university believes that the claim is justified that people in Thailand should have access to this medicine.”
According to Chokshi and Sturm, the WARF-Zemplar situation is similar to that of stavudine, for which a license had already been negotiated between Yale and Bristol-Myers Squibb. However, barriers existed that kept South Africa from affording the drug or importing generic versions.
Humanitarian group Doctors Without Borders subsequently asked Yale and BMS to allow South Africa to import a generic version of the drug; and the Yale professor who discovered the drug authored an op-ed piece, published in the New York Times, that called for BMS to act. This put public pressure on BMS to expand access to the drug, Chokshi said. In 2001, BMS said it would no longer attempt to stop generic drug makers from selling low-cost versions of the drug in Africa
“This is the difference in thinking,” Chokshi said. “If you believe that this is a bad decision by Abbott, then the university has some responsibility for trying to change that decision.”
Harvard Sets an Example?
Also earlier this month, Harvard seemingly “put the rubber to the road” when it announced a licensing deal with China’s Morningside Group for vaccine technology developed by John Mekalanos.
Mekalanos’ technology is called the protein capsular matrix vaccine. The PCMV, according to Harvard, enables pharmaceutical companies to produce vaccines rapidly and inexpensively; and to more easily develop multivalent vaccines – a potentially important technology in developing countries because can protect against multiple pathogens in one vaccination. A patent application for the technology is currently under review by the US Patent and Trademark Office.
Under the terms of the agreement, Morningside will form a new company that will develop and commercialize the PCMV technology and ensure that vaccines incorporating the technology are made available at “reasonably affordable prices” in countries eligible to receive support from the Global Alliance for Vaccines and Immunization, Harvard said in a statement.
In addition, Harvard has agreed to relinquish its share of future royalties on sales made by Morningside’s company and its affiliates in GAVI countries, and has reserved the right to directly license qualified governmental bodies and non-governmental organizations to distribute vaccines made with the PCMV technology for humanitarian purposes, the university said.
In an e-mail to BTW, Larry Schlossman, director of business development at Harvard’s Office of Technology Development, wrote that the school chose to partner with Morningside Group primarily because of its willingness to negotiate socially responsible terms into the license agreement.
“What we were hoping to inject into this debate is some level of specificity, because unfortunately it is all too easy for university decision-makers to agree to this general principle of what should be done, but when the rubber meets the road, it doesn’t make a difference if all that is talked about is this high-level principle.”
“Like vaccine manufacturers or biotech companies in the US, we believe that Morningside has the technological and other resources to develop this vaccine platform and bring products successfully to market,” Schlossman wrote. “Unlike other potential partners, however, Morningside was willing to adopt the technology at an early stage and, despite the typically long time to launch of a vaccine product, to address Harvard's and Dr. Mekalanos' concerns regarding global access.”
Schlossman added that the agreement grants Morningside a worldwide license to Harvard's PCMV patent rights and, “except as regards royalties in GAVI countries, contains financial terms typical of academic-to-industry licenses to therapeutic or vaccine platform technologies.”
Chokshi called the deal “laudable,” and Sturm said that it was “wonderful” that Harvard has waived its royalty rights to the PCMV technology.
Both, however, also expressed reservations about the agreement, stressing that it would take time to see if Harvard backs up the terms regarding expanded access to the technology in developing nations.
“[Waiving royalties] really only reduces prices at the margins,” Sturm said. “We’ve seen over time that the most important factor to bringing down the price of drugs is allowing for generic competition. That drives the price down very fast.”
Chokshi said that Harvard has “done the right thing with respect to this one circumstance,” but added that the agreement raises questions about “why they’re only considering these types of provisions, for example, in a license to a developing country manufacturer for the purpose of supplying to developing countries.”
The agreement, he said, “should be quickly followed with evidence that this idea of socially responsible licensing extends not just to technologies for neglected diseases, but also for any technology that comes out of Harvard’s research enterprise.”
Chokshi explained that a distinction needs to be drawn between “global diseases” and neglected diseases that primarily affect poor countries. In the case of global diseases such as cancer, HIV, and cardiovascular disease, Chokshi said that access-minded licensing terms – such as allowing generic competition or engendering lower prices in poor countries – are needed because there is an incentive for companies in the developed world to take a university technology and turn it into a medicine.
“The second case is more in line with [the] Morningside and Harvard [agreement],” Chokshi said.
Harvard’s Schlossman wrote that “it is our understanding that the profit margin on most vaccine products is low,” and explained that waiving royalties in developing countries is “one tool” for reducing vaccine production costs.
“While we do not favor a one-size-fits-all approach, as UAEM does, given the unique nature of each licensing arrangement, Harvard avails itself of what we believe are creative and innovative strategies in addition to royalty reductions/waivers to accomplish humanitarian distribution of key medical innovations,” Schlossman added.
The recent actions of Harvard and other universities that have considered widespread adoption of UAEM’s suggested policies – many of which contributed to the “socially responsible” licensing white paper earlier this year – have created momentum for the movement, Chokshi said.
“We know of about a dozen major research universities that are seriously considering these types of changes,” he said. “But those universities now need to have some sort of inter-university collaboration to proactively say they are interested in this and to meet that principle with some statement of commitment to actually make the changes.”