DNDi: “Bench-To-Bedside” Approach Needed For Drug & Vaccine Response To Global Health Crises

Global health policymakers need to adopt a “bench-to-bedside” approach to research and development, to ensure that new drugs and vaccines are not only put into the development pipeline, but are also readily available for responding to global health crises such as Ebola, says Michelle Childs of the Drugs for Neglected Diseases Initiative (DNDi).

Childs, DNDi’s head of policy and advocacy, was a key speaker at a seminar this week with industry, civil society, and UN representatives on “Policies and Practices for Effective Response to Global Health Crises,” sponsored by the World Intellectual Property Organization (WIPO).

The day-long seminar on Tuesday (16 April) brought together the diverse groups to share success stories and exchange views about how intellectual property (IP) can either be an enabler of innovation, or a barrier to access that hinders effective emergency response to crises such as the recent Ebola outbreak in the Democratic Republic of Congo, which has so far killed over 1,000 people.

“It is clear that new models of financing, new models of private development that involve public financing, must be considered and taken forward,” said Soumya Swaminathan, the World Health Organization’s newly-appointed chief scientist, and the keynote speaker at the seminar.

“The innovators obviously deserve some credit and some returns, but this cannot be at the expense of people who need the products,” she said, citing challenges that range from Ebola to lack of access in many countries to basic health products such as insulin for diabetes as well as “huge problems of antimicrobial resistance.” She noted that “it has been warned that we may be back to a pre-antibiotic era, when there was no penicillin and you just hoped for the best. So, if we want to avoid that situation… there needs to be discussion, global discussion and solutions found.”

While industry and civil society representatives on a panel expressed differing views, they sounded a common theme on the increasing importance of public-private collaborations to respond effectively to new and looming crises and threats, ranging from Ebola to antimicrobial resistance (AMR).

However, too often now, there is a lack of continuity between early-stage public-private R&D collaborations and final policies on drug registration and access, pointed out Childs from DNDi. She said a more holistic approach is needed to overcome the current barriers. It is an approach that DNDi has modeled in its development of eight new treatments for neglected diseases such as malaria, sleeping sickness, visceral leishmaniasis and Chagas disease since 2007 – all easy-to-use, affordable, and not under patent.

There is also a new combination therapy (sofosbuvir + ravidasvir) for Hepatitis C in advanced stages of clinical trial, which should make these lifesaving drugs available across wide swathes of Latin America and South-East Asia, which aren’t currently covered by license arrangements for other inexpensive generic formulations.

“R&D is a kind of relay race, what you need to do is to make sure that each stage can develop, and then ensure that we can reach the next stage. We are trying to create collaborations that extend from research to implementation.”

In that context, it has been likewise critical for DNDi to ensure, upfront, that a clear IP and access policy will facilitate not only development, but also a clear distribution strategy offering broad access to drugs funded by public monies and developed by the public-private partnerships it fosters.

“There is innovation capacity in many regions of the world,” she observed. “This can include big and small companies, ministries of health, and more. But any agreement we reach, must ensure that we can have affordable treatment for the people that need it.” That has to include provisions such as the open publication of research data, whenever possible. Agreements with private sector partners should include provisions that drugs developed with DNDi support can either be marketed as generics [or other comparable arrangements], or if built upon a pre-existing patent, licensed at affordable prices.

“We won’t enter into any partnership without overcoming any IP barriers,” she stressed. “We aim for anything that is developed to be developed as a public good,” she said, adding in a subsequent interview.

“Because we go from bench to bedside, we need to be able to ensure that it can be made available at an affordable price to all endemic countries.”

A contrasting view, however, was offered by Tomas Cihlar, vice president of virology at Gilead Sciences. He said that recognition of IP rights can in fact help enable and accelerate the rollout of generic versions of a drug. Cihlar recalled how Gilead initiated a programme of voluntary licensing of its cutting-edge anti-retroviral drug therapies for HIV to generic companies in India in the mid-2000s significantly reducing the medicine’s cost, as an example of how industry can act proactively in the public interest.

“We [Gilead] did not want to wait until the IP [patent] expired for our branded anti-retrovirals,” Cihlar said, “so we went ahead of the game and entered the process proactively.” The company also supported the transfer of technology to the generic companies “so that the process was much faster, more effective, and more successful.”

Yet in taking those moves, the “IP system allowed Gilead to have some stability in the system,” he said. The generic companies now supply drugs to some 140 low- and middle-income countries worldwide at a fraction of the cost of the branded medicines. This has enabled access to the Gilead formulations of HIV medicines for some 12 million people living with HIV – although he also noted that close to 1 million estimated deaths annually from HIV/AIDS reflect the ongoing lack of access issues. “Drug accessibility is not equal around the world, and that gap should be further studied, defined and addressed.”

Fast forward to the 2014 Ebola outbreak, when Gilead entered a public-private partnership with the US Centers for Disease Control and the Department of Defense, which resulted in the discovery of a novel anti-viral drug, Remdesivir. The drug is now being used in the current Ebola outbreak in the eastern Democratic Republic of Congo (DRC), together with several other investigational drugs, as part of the outbreak response led by the DRC Ministry of Health in collaboration with WHO and numerous NGOS such as MSF, as well as drug developers, including Gilead.

He said that Gilead started building the key partnerships with WHO and other institutions proactively in the wake of the initial 2014 outbreak, and as a result these institutions were familiar with Remdesivir, when Ebola re-emerged last year. This, in turn, enabled its fast implementation for the present-day outbreak response in DRC under ‘compassionate emergency use’ protocols, governing use of experimental therapies that are not [yet] fully registered, and subsequently in an ongoing randomized controlled trial.

“For me, this is a significant manifestation of corporate social responsibility, where we provided these key resources to support addressing an urgent outbreak and global health challenge such as Ebola,” he said.

Intensified public-private collaborations have been similarly critical in rushing an experimental vaccine against Ebola into use, noted Merck’s executive director for Public Health Partnerships, Amir Khan. The experimental drug, known as rVSV-ZEBOV-GP, has recently shown great promise, reducing mortality in over 88 percent of people who had come into contact with Ebola victims and were then vaccinated, according to results released earlier this month by WHO and the DRC’s Institut National pour la Recherche Biomedicale (INRB), which are collaborating in the trial along with MSF and the DRC Ministry of Health. The trial is supported by the Wellcome Trust, the United Kingdom’s Department of International Development (DFID), Gavi – The Vaccine Alliance and the World Bank.

“It is like flying a plane while you are still building it,’’ Khan said. “We are trying to get this vaccine out there while we are still developing the process. But if it wasn’t for this sort of collaboration, the investigational vaccine wouldn’t have gotten out there as fast as it did.”

Khan cited the new Coalition for Epidemic Preparedness Innovations (CEPI), an innovative collaboration of governments, UN agencies, foundations and the private sector on research into vaccines for other neglected diseases, as an example of “what we can learn from the Ebola response outbreak” and apply to other looming threats that currently lack effective responses. He said that the CEPI approach was to have “the world come together to work on these pathogens before they become the next Ebola, getting ahead of the next outbreak.”

However, Médecins Sans Frontières (MSF) Senior Policy Advisor, Katy Athersuch, told seminar participants that the Ebola vaccine’s development history also underlines the pitfalls of the current system which puts profit over public health goals even when research is publicly funded. In this case, the Ebola vaccine candidate was actually discovered some 15 years ago by scientists at the Public Health Agency of Canada, which later licensed the IP to a subsidiary of the US company NewLink Genetics, funded by the US Department of Defense, “for the maximum commercial return to the Company and Canada.”

Only after the largest-ever Ebola epidemic had started in Guinea in 2013, did NewLink, PHAC, WHO and the US National Institutes of Health begin planning clinical vaccine trials. Then in 2014, Merck purchased the exclusive rights to the IP – for 25 times the original sale price by Canada, according to Athersuch.

“It is good to hear Merck saying they are now aggressively pursuing licensure, but it’s taken too long,” Athersuch said in a follow-up interview with Health Policy Watch.

“Arguably this is hindering the response, as the vaccine needs to be given as an experimental product under trial conditions. Last week over 40% of the newly reported Ebola cases in the DRC were people who died in the community, before they could be identified as Ebola patients and offered care. This is a major problem. We need to expand the use of vaccination in a preventive manner and to a larger population. Doing so would be much easier if we had a vaccine registered for use. And even now the vaccine is still not registered with the EMA, FDA or in the DRC.”

“This profit-driven arrangement did not put public health first,” she observed. “For MSF, this demonstrates why we need a better social contract to govern the development of critical medicines like this vaccine.”

Similarly, on CEPI, she voiced concerns that the organization’s five-point access policy which has now been published in detail online at the end of March, still has major gaps, in comparison to model approaches being used by organizations such as DNDi.

She said the access policy only covers the R&D stage – “there’s nothing requiring those they fund to seek licensure/registration (no timeline, or mention even), and when they focus on access it’s access to an ‘investigational stockpile’, so access to the unlicensed product for use in trials during an outbreak.”

“Investigational products for use in trials are almost always donated. They are investigational, that is to say they have not yet achieved marketing approval so necessarily can’t be marketed and sold! And more importantly, these are not ‘free’, they are paid for up front by CEPI, who put specific money in the grants to finance these stockpiles. Paying for something in advance is not the same as it being ‘free’.”

Finally, in the template terms and conditions, published on the CEPI website, awardees of CEPI grants “own” all of the project results, including “intellectual property, materials, any Product and Investigational Product, publications, reference standards, technology and other results.”

Said Athersuch, “CEPI is not retaining its most valuable asset, the IP and the products that it has financed through these projects. CEPI needs to be thinking about access post-approval when we have a successful vaccine that we need to continue to use. CEPI needs to chart a new model in affordable access to vaccines.”

Despite the disagreements about how best to fast-track R&D while also ensuring broad access, there was “widespread agreement that innovation in health emergencies takes many forms, including lab-based innovation, operational innovation, and social innovation,” said Marion Dietterich, director of WIPO’s Global Challenges Division and the concluding speaker at the seminar session.

“Several themes emerged… such as the importance of partnerships and sharing lessons learned, both successes and failures. Panelists and participants also coalesced around the idea that innovation to support stronger, more efficient collaboration is vital – because while urgency is often defined and experienced locally, readiness and response requires global cooperation.”

Image Credits: MSF, DNDi, MSD.

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