Center for Global Health R&D Policy Assessment

AVAC: Global Advocacy for HIV Prevention appreciates the chance to discuss the affect on research and development for new products contained in this evaluation of joint IP management arrangements (JIPM) and patent pools (ch. 3 of the report). In 2005 and 2010, AVAC reported its findings and recommendations on IP barriers, data and materials sharing and management and technical know how in the context of progress towards discovery of an HIV vaccine. http://www.avac.org/ht/d/sp/i/2510/pid/2510

The RDI report examines the JIPM arrangements of drugs for neglected diseases rather than biologics. In the case of HIV drugs, the report does not consider R&D aspects but instead (chs. 1-2) reviews a post marketing pool proposal for access to HIV drug generics. We believe HIV R&D acceleration in the new international effort towards discovery of an HIV cure also benefits from study of alternative effective JIPM and that vaccine research models provide valuable lessons towards that goal.

In contrast to incentives for some neglected disease research efforts, an HIV cure may have a substantial global market, At this early stage of the research, the effort is not Product Development Partnership (PDP) driven. Private sector, academic, government and foundation supported research appears to be growing along with competition to lay claim to an exponentially increasing IP landscape of therapeutic compounds, new laboratory assays, volumes of underlying data and terms of use for materials. Therapeutic drugs, including the repurposing of some existing chemical compounds (e.g. some expensive HDAC inhibitors and some inexpensive natural compounds) and the invention of new drugs, is a major component of that race to the finish. Overlapping, blocking, or thicketed claims and secrecy can be expected to affect the pace of research.

The international cure research effort – collaborative to a very welcome degree under an NIH sponsored grant - has not yet herded all of the potential IP within a publicly organized consortia of cooperating efforts as has been the case with some HIV vaccine research. Vaccine consortia, such as CHAVI or the CAVD, organize the work of hundreds of global labs within model membership and MTA agreements exhibiting JIPM and pool-like features . These JIPM arrangements increase freedom to operate, share IP during precompetitive periods and distribute data and materials that may otherwise be kept private.

We recently saw an example of their accelerating benefits. Hundreds of cooperating international investigators worked tirelessly to report findings to explain correlates of protection from the RV 144 vaccine trial in Thailand. The vaccine consortia could be improved and provide additional JIPM appealing to the private sector and others, but they are an excellent alternative model to study In greater detail beside the unique special purpose pool now used in the RDI report.

AVAC appreciates the great contribution to policy development reflected in the current report draft and offers these comments as a way to expand its scope a bit further. Finally, we also believe that effective JIPM applied to early stage research has the potential to mitigate and avert many of the difficulties experienced now by the HIV MPP for generic drugs when innovative brand products finally come to be distributed and access is given to all who may benefit.

The lack of funding and incentives for neglected disease research and development (R&D) requires new, open, and transparent models for sharing intellectual property (IP), including confidential knowledge and research data.

The World Health Organization (WHO) Global Strategy on Public Health, Innovation and Intellectual Property, among other things, aims to “encourage and support the application and management of intellectual property in a manner that maximizes health-related innovation, especially to meet the R&D needs of developing countries, protects public health and promotes access to medicines for all.”

As outlined by the consultation draft of Results for Development’s (R4D), the Pool for Open Innovation Against Neglected Tropical Diseases and the Medicines Patent Pool (MPP) are clear illustrations of a trend towards a more open environment to boost innovation for diseases prevalent in developing countries.

However, there are differences in approaches taken by both initiatives to address the issue of access. The Pool for Open Innovation Against Neglected Tropical Diseases offers royalty-free licenses for sales in least-developed countries (LDCs) and leaves open for negotiation royalty rates for sales in other countries, at the discretion of IP holders. The MPP aims at negotiating licenses covering all developing countries. Although the first license signed between the MPP and a pharmaceutical company (Gilead) only includes 100 to 112 developing countries , depending on the licensed product, this is relatively broader than 49 LDCs.

In our view, the R4D consultation draft does not sufficiently acknowledge the need for such open innovation initiatives to build upon the many reports and international negotiations on IP, innovation, and public health of the past 10 years. In particular, it does not adequately address the issue of access to the pools’ outputs for all neglected patients. We believe this is a step backwards with respect to the 2008 WHO Global Strategy and other multilateral recommendations.

As a not-for-profit R&D organization developing new treatments for neglected patients suffering from NTDs such as sleeping sickness, visceral leishmaniasis, and Chagas disease, as well as malaria and pediatric HIV, DNDi’s firsthand experience with IP management can be instructive. DNDi’s IP policy is guided by two fundamental principles: (1) to ensure that drugs developed by DNDi are affordable and access is equitable for patients who need them, and (2) to develop these drugs as public goods whenever possible.

As per its policy, DNDi “negotiate[s] terms with partners to ensure that they will not use the acquired and/or held IP in a manner that impedes equitable and affordable access to the products of the research, or that impedes additional or follow-on research by DNDi, its partners and other researchers, especially those undertaking research on neglected diseases. DNDi will not accept projects in which IP is obviously going to be an insurmountable barrier to follow-up research on behalf of DNDi and/or equitable and affordable access.”

Since its inception in 2003, DNDi has delivered five new treatments that are safe, effective, field-adapted, affordable, and non-patented. For two of these treatments – the fixed-dose anti-malarials artesunate and amodiaquine (ASAQ) and artesunate and mefloquine (ASMQ) – DNDi’s IP policy has been applied in a manner than has both ensured equitable access and enabled technology transfer. In addition, DNDi has signed research collaboration agreements with major pharmaceutical companies to research and develop new compounds for neglected diseases with provisions reflecting the above IP policy.

Access conditions for new neglected disease treatments cannot be left open for negotiation at the end of the R&D process, as illustrated by the example of AmBisome. This liposomal form of amphoterin B was developed by Gilead for the treatment of fungal infections, but turned out to be very effective for visceral leishmaniasis (VL) – a single injection cures over 90% of patients in India. AmBisome was registered for the treatment of VL in the early 1990s after a multi-country trial, supported in part by the WHO Special Programme for Research and Training in Tropical Diseases (TDR), showed its efficacy. However, the cost for a treatment remained high at $2,000 per patient and was inaccessible for over 15 years while poor people were dying due to antimonial drug resistance. After years of advocacy by Doctors Without Borders/Médecins Sans Frontières (MSF) and others, Gilead realized that they were not making any profit from poor countries anyway and agreed to reduce the price by a factor of more than10 for certain countries indicated by WHO. Had access been considered a key part of the R&D strategy from the beginning, patients would not have needed to wait 15 years for this important therapeutic breakthrough.

A more open IP framework is needed to facilitate and foster neglected disease R&D by the few entities involved in neglected disease research, but access issue needs to be addressed very clearly. Such a framework would also support international procurement and distribution mechanisms that will be necessary to overcome market failures and ensure access to neglected disease health tools for patients with little ability to pay.

Thanks again for allowing comments on this draft. In brief, I agree with Jon Pender who is quoted on page 44, that patents are not the main barrier to neglected disease drug development, it's market incentives. For more on m ideas about markets incentives see my blog at http://cdippel.wordpress.com/. I'm also sending more specific comments to the report authors.

As the third-party non-profit administrators of the Pool for Open Innovation against Neglected Tropical Diseases (“the Pool”), BIO Ventures for Global Health (BVGH) appreciates the opportunity to have the project featured in this paper, and for the opportunity to provide feedback on this draft.

In general, BVGH’s primary reaction is that the paper appears to overemphasize the Product Development Partnership (PDP) audience when assessing the Pool. Although PDPs play an important role in neglected disease drug discovery, these organizations are not the primary target as users of the Pool. In fact PDPs are not likely to be as interested, in part for the reasons identified in the paper and which are understood: the PDPs typically have an established presence in a disease state, have established relationships with relevant pharmaceutical companies and others -- even funders -- who are active in the field, and thus have access for the kind of introductory discussions with a potential collaborator that the Pool offers.

Instead, the target user audience is the broader neglected tropical disease research community, primarily the early stage researchers (most often academics and public sector institutions, as the paper notes) who might benefit more from having access to the kind of assets the Pool intends to provide. It appears that very few potential users from this group were interviewed. The authors acknowledge this lack of perspective in the paper, but we would hope that scope might be expanded.

With these limitations in mind, we do appreciate the important suggestions made in the concluding sections, including expansion of the Pool to include Chagas disease, focusing on certain aspects of the Pool (e.g., know-how and compound data versus patent information), and continuing to clarify and effectively communicate the value of the contents of the Pool.