The World Health Organization announced Wednesday that it would implement a pilot programme to include human insulin products in its Prequalification of Medicines programme, in an effort to expand access to treatment for diabetes in low- and middle-income countries. The move is the first in a series of steps WHO is taking to address the growing burden of diabetes, which is now one of the top ten leading causes of death around the world.

“Diabetes is on the rise globally, and rising faster in low-income countries,” says Dr Tedros Adhanom Ghebreyesus, WHO Director-General in a press release. “Too many people who need insulin encounter financial hardship in accessing it, or go without it and risk their lives. WHO’s prequalification initiative for insulin is a vital step towards ensuring everyone who needs this life-saving product can access it.”

Human insulin has been on the WHO Essential Medicines List since 1977, which guides many national government decisions about products to support in public health services. However, only about half of the 65 million people with Type 2 Diabetes who need insulin can actually access it, WHO estimates, due to the high prices of insulin products and unavailability in public health facilities.

Currently just three pharmaceutical companies – Novo Nordisk, Eli Lilly, and Sanofi – control most of the global market for insulin products, and prevailing prices remain prohibitive for many people and low-income countries, and even in some high-income groups as well.

Including insulin in WHO’s Prequalification of Medicines programme, would make it more attractive for new competitors to enter the market – by submitting proposals to WHO review for production of quality-assured insulin products at lower prices. WHO prequalified products also are used as the basis for many donor-supported initiatives to make bulk purchases of products at preferred prices for low- and middle-income countries.

The ultimate result, WHO officials believe, would be an increase in the number of quality-assured human insulin products on the international market, and a wider range of choices for patients at lower prices.

“Prequalifying products from additional companies will hopefully help to level the playing field and ensure a steadier supply of quality insulin in all countries,” said Dr Mariângela Simão, assistant director general for Medicines and Health Products at WHO.

A WHO spokesperson told Health Policy Watch that already, at least three new market entrants have informally expressed their interest in applying for WHO Prequalification as part of the pilot.

“Clearly we hope more come forward now that the pilot is official, because clearly the more companies that meet international quality standards, the larger the chance that insulin will become affordable,” said the spokesperson.

The target WHO assessment time is 270 days, meaning if companies submit their applications within the next few months, new WHO-prequalified products could be on the market as early as this time next year.

Prequalification is a process in which WHO evaluates the quality, safety, and efficacy of medical products and issues guidance on their use. Many low- or middle-income countries also see WHO prequalification of a product as a stamp of approval to begin registering the health product for use in their own countries.

Access To Insulin A Global Challenge

From 2016-2019, human insulin was available only in 61% of all health facilities and analogue insulins (altered forms of human insulin) were only available in 13%, according to WHO data from 24 countries. The data showed that a month’s supply of insulin would cost the average worker in Accra, Ghana almost a quarter of their monthly income.

Even in high-income countries, the high price of insulin results in many people rationing its use, which can be deadly for people who do not receive the appropriate daily dose.

Globally, some 422 million people live with diabetes. Diabetes is the seventh leading cause of death globally and a major cause of costly and debilitating complications such as heart attacks, stroke, kidney failure, blindness and lower limb amputations.

People with Type 1 diabetes need insulin for their very survival and to maintain their blood glucose at levels to reduce the risk of common complications such as blindness and kidney failure. People with Type 2 diabetes need insulin for controlling blood glucose levels, and to avoid further complications when oral medicines become less effective as the illness progresses.

Decision Follows Debate Over Inclusion of Analogue Insulin in WHO Essential Medicines List 

WHO’s decision to pilot human insulin prequalification also follows a contentious debate earlier this year over the proposed inclusion of still more pricey insulin analogues (altered forms of human insulin) in WHO’s Essential Medicines List (EML). The list is used by many countries as a basis for national decisions on the basket of medicines to be procured, offered or supported.

Civil society, scientific experts, and patient access groups opposed the petition to include analogues in the EML, arguing that including these products without addressing the lack of competition in the insulin space could send the wrong message to governments, making analogue insulin the new norm. And that could actually drive up prices that low- and middle- income countries were paying for insulin products.

The Pre-Qualification initiative appears aimed at addressing some of those existing needs and gaps. Health Action International (HAI), one of the same civil society groups that opposed the petition to include analogues in the EML, commended the WHO’s decision to include human insulin in the prequalification program.

Dr. David Beran, University of Geneva professor and co-lead investigator of a HAI study group focusing on insulin access (ACCISS) expressed his hope that WHO’s decision will impact the limited competition in the insulin market in a statement released by the group. “This initiative should ultimately lead to greater competition and hopefully lower prices, thus improving affordability for people and health systems.”

This story was updated November 14.

Image Credits: WHO.

With rates of self-harm, suicide and anxiety among children and young people growing around the world, UNICEF and the World Health Organization hosted the first ever “Leading Minds” Conference to tackle adolescent mental health on November 7-9. The forum highlighted the growing recognition of mental health as a global health problem, and follows moves made earlier this year by WHO to scale up social media campaigns for suicide prevention and implement a new Special Initiative for Mental Health.

“Around the world, 1 in 5 children and adolescents live with a mental health condition, such as depression or anxiety. Children living in poverty, or exposed to war, violence at home, or other difficult life situations, are particularly vulnerable. Very few of these young people have access to the [mental health] services they need,” said Dr Tedros Adhonym Ghebreyesus, director-general of the WHO.

“We need to break the silence and eliminate stigma. We need to find better ways to reach young people, through their families, peers, schools and online channels, and help them thrive.”

The first ever such forum co-hosted by UNICEF’s research center Innocenti and WHO in Florence, Italy brought together a variety of stakeholders from different sectors to develop recommended actions to tackle mental health in young people. The by-invitation only forum featured experts such as the Minister of Health of Kazakhstan, who discussed how their country mainstreamed adolescent mental health care into the education and health systems.

Experts at the conference noted the importance of shedding light on adolescent mental health as a particularly neglected area in the mental health space.

“Total development spending and government spending in mental health care make up less than 1% of overall health spending. And less than 1% of that amount is spent on children and young people,” Dr. Vikram Patel, a professor and adolescent health researcher at Harvard Medical School, pointed out in a video from UNICEF Innocenti.

He noted that adolescent mental health is still an area where researchers know very little. This is mostly because most research in mental health has been conducted on adult mental disorders, and mental health problems in young people “don’t fit neatly into these sorts of biomedical activities.”

Despite the lack of knowledge, investing in young people’s mental health is both a “moral and practical, economic” imperative, said Henrietta Fore, executive director of UNICEF, in her opening statement. Since half of all lifetime mental health disorders manifest before the age of 14, early detection, prevention, treatment and rehabilitation is key to “avoid further social and health care costs down the road,” she argued.

Dr. Tedros agreed, calling on all countries to invest in adolescent mental health as part of their efforts to expand Universal Health Coverage.

“After all,” he said, “There is no health without mental health.”

Image Credits: Twitter: @WHO.

MMV CEO David Reddy talks about the steps MMV is taking to support a new generation of malaria research leadership, promote more gender-sensitive malaria treatment and fast-track innovation on new malaria combination therapies. This follows a string of MMV successes over the past two decades in fostering new paediatric malaria treatments, new combination therapies to fight drug resistance and a breakthrough single-dose treatment, tafenoquine, for the relapsing form of malaria.

Health Policy Watch: You are celebrating the 20th anniversary of MMV’s creation. It was also one of the first non-profit “product development partnerships (PDP)” to be created, involving both industry and public sector actors in malaria R&D. How did MMV come about, and what gap has it filled in the R&D landscape?

David Reddy: MMV was formed in 1999, out of a WHA discussion with African leaders who were worried that there was more parasite resistance developing [to existing malaria drugs] and not enough R&D being done on new treatments, effectively there was a market failure.

It came out of the forward-thinking people in Industry and WHO, and incubated at the TDR, the Special Programme for Research and Training in Tropical Diseases.

Today we have a broad partner network, including some 26 pharma partners, both innovators and generic producers, as well as research and academic institutions, governments, international organizations, NGOs and non-profits, and clinical trial centres in endemic countries.

For the past two decades, MMV has been leading the development of new antimalarial treatments, supporting expansion of R&D capacity in malaria-endemic countries, and working to ensure access to antimalarial treatment by the world’s most neglected populations.

HP-Watch: We have heard you recently speak about how MMV had its roots in industry, while Drugs for Neglected Disease Initiative DNDi), had its roots in civil society activism – but you both have gotten to a similar place in your development. Can you talk a little more about that?

Reddy: Well, I compare it to the blue whale and the whale shark.  On the evolutionary tree, DNDI and MMV started from different places, but we are addressing the same underlying issues in the drug development ecosystem – market failure. In addition, we at MMV, we focus solely on malaria whereas DNDi’s remit is wider in terms of neglected tropical diseases.

Because of where we came from, we started from a strong R&D base; there were a lot of people from industry who became part of MMV.  So, I think we were positioned very well in terms of being able to get industry to contribute to the model.  Additionally, I have led teams [while at Roche] that had developed drugs with regulators, so I also know that mindset. And in fact, the regulators are quite agnostic about whether the innovation comes from industry or a non-profit group – the same rules apply.

HP-Watch: There has been a lot of discussion recently about the importance of insuring for wide access to treatments up front. When MMV engages with the private sector or others. What’s MMV’s approach on that, and how is it similar or different to others?

Reddy: In every agreement we have with our partners, we build in access and affordability clauses.  Those include two elements: a commitment to make the drug available and affordable in malaria-endemic countries.  We generally define what that means and in the context of affordability we have enforcement clauses, as well. If a partner doesn’t live up to those obligations, we can take action, such as moving manufacturing capacity across to another partner.

HP-Watch: Is there a motive for pharma to participate if the costs are kept low?

Reddy: Because of the sheer volume of the malaria drugs that need to be provided, [there is still an incentive]. It is a real challenge for other disease areas, where the populations are smaller. For some of our partners, the motive is corporate social responsibility. Others take a no-profit, no loss approach. Incentives such as the US FDA Priority Review Voucher programme can be important.  A partner can use a voucher (awarded upon approval of a new neglected disease treatment to get a rapid approval of another drug in a profitable disease area, where a six-month time to market advantage is worth a considerable amount of money.  And once the vouchers have been issued, they can also be transferred and sold. These kinds of benefits do help tip the balance of the pharma companies participating in this area.

HP-Watch:  Can you briefly summarize the 3-4 biggest breakthroughs you have experienced in drug development – up to the recent approval of the new drug tafenoquine – and their meaning for public health?

A health worker dispenses a child-friendly formulation of Coartem®, MMV’s first paediatric malaria treatment.

The first breakthrough was the product we co-developed with Novartis, that was a child-friendly version of their antimalarial drug, Coartem®, [the first artemisinin-combination therapy]. In less than ten years since launch, some 385 million courses of that treatment have been delivered.  This is a key success since most people who die from malaria are children under 5 years of age. And yet children are among the last to get [paediatric formulations of] medicines [due to the sensitivity of clinical trials involving children]. So, this was really important.”

Pyramax® (pyronaridine-artesunate), is another ACT – based on the drug pyrimidine, that has shown some nice activity in areas where resistance has been seen.

Testing for malaria (P. vivax) parasites in Brazil, the first malaria-endemic country to approve the first GSK and MMV co-developed treatment for relapsing malaria.

This is a particularly important development programme because we are working with a generic company, Shin Poong in South Korea, and they formed a joint team with us.  We were able to bring our knowledge of drug development and the malaria space to them and help bridge the gap between generic companies and innovators. So, it was a capacity development journey for them and for us it was useful in getting the product on the market.

Then, just last year, tafenoquine, which was developed in partnership with GSK and is a single dose cure for the relapsing form of malaria (caused by the Plasmodium vivax parasite), which in some patients can replace 14 days of treatment with the currently used drug. Tafenoquine was approved by the US FDA and Australian TGA. It has also just been approved by the Brazilian regulatory authorities.

 

A child receives injectable artesunate for severe malaria, a formulation that MMV is helping generic manufacturers produce.

In addition, we are supporting generic manufacturers to produce quality-assured variations of rectal artesunate and injectable artesunate, [for immediate treatment of severe malaria episodes]. This was massively important in terms of getting these products onto the WHO Pre-Qualification list, [which undertakes a stringent review and can be a pathway for approval by national regulatory agencies]. For the injectables alone, some 144 million vials have been shipped since 2011, and we estimate that has saved 950,000 more lives in comparison to the alternative treatment, injectable quinine – if people were even to receive that at all. For the suppositories, some 3.2 million have been shipped since 2017, and we estimate about 300,000 lives have been saved.

HP-Watch: What about malaria resistance… how serious a threat is that, where and what is MMV doing about it?

Reddy: There is resistance being seen with some of the ACTs – current first-line treatment for uncomplicated malaria. o\On that basis, we are developing, with Novartis, a new combination of novel compound ganaplacide with a new formulation lumefantrine. This is a non-artemisinin-based combination, which is what we need to be looking for, with a new mechanism of action against resistant parasite forms. It is in Phase 2b studies, and we are hoping it could be a one- or two-day therapy. That would provide a big benefit, in terms of its utility because one of the big challenges that we have seen with the ACTs [which have a 3-dose regimen] is that while people will take the first and second dose, there is a tendency for people to hold back on that last day of dosing, if they are feeling better, thinking that they can save the pill until the next child gets sick. And that fosters resistance.

Resistance is something that needs to be taken really, really seriously, we have seen it in each of the malaria drugs that have been developed, which is why using them in combination is so important.

So, we are trying to pursue an approach where multiple approaches for first-line therapy are available in every country, keeps the pressure on the parasite. Secondly, we are trying to develop new combinations with new mechanisms of action, like the Novartis project I just mentioned. Towards this end, there were 5 biological targets – ways we could hit the parasite – 20 years ago. Today there are 25 targets, and this can give rise to entirely new drugs; a number of them are already in clinical development.

Malaria parasite (blue-left) attaches to a human red blood cell (red-right)

We see the parasites being resistant to the drugs, we see the mosquitoes becoming resistant to the insecticides. We even see the parasites developing a form of resistance to the rapid tests that we use to identify them. In some of the tests, they had worked out a way to escape the test, by deleting a part of their genome that gave rise to a protein used by the rapid test to detect them. This multi-layered counter-offensive is something as a biologist that I have never seen.

The threat of resistance is compounded by other regional or global changes.  For instance, with climate change you get flooding, destruction of infrastructure that reverses the development progress that has been made. The other challenge is political instability, you can see that in the resurgence of malaria in Venezuela.

HP-Watch: The theme of malaria “eradication” has been much in the news, with some agencies saying it’s feasible and WHO saying that the elimination agenda first must get back on track. What’s your view?

Reddy: There were two reports on this topic that were launched a few months ago, one was by the Lancet Commission and one was by the WHO Strategic Advisory Group on Malaria Eradication (SAGEme).  Both effectively came to the same conclusion, which was that eradication should be our objective.  The WHO report [also] said that there is no biological impediment for why it cannot be achieved. But we will need new interventions.

I believe in the feasibility of eradication. What it requires is systematic elimination from countries and regions, as we have done it in Europe and North America. [It also requires a change in mindset], because many people have this inherent belief that the countries in Africa are locked into malaria.

Hans Rosling, in his book Factfulness said that countries in Africa have developed beyond most people’s understanding, at a strong pace. African countries are showing strong ownership of the concept of eradication and they are putting resources behind it. We have seen enormous progress in pushing back malaria, and a number of countries are on the cusp of elimination of malaria [as a public health risk]. But in other countries, we need to do more, including getting more real time data on what is working and what is not.  Groups such as USAID Presidents Malaria Initiative, the Global Fund and the Gates Foundation are really putting processes in in place to get better real time access to data that is needed. And part of it is up to us, to bring a new generation of medicines forward for prevention and treatment. We have made enormous progress; we have entirely new ways of attacking the parasite. Now it’s a matter of getting innovations through development and into the hands of clinics and patients.

HP-Watch: Some critics have accused the health sector of abandoning vector control, including environmentally-friendly measures such as better management of water resources and housing (e.g. screening) as modes of “treatment”, which can also reduce reliance on chemicals, and therefor vector resistance to chemical tools.

Reddy: I think vector control is being addressed from a different angle, the developmental angle.  We do see significant developmental progress and there will be a positive collateral effect on malaria. The Zero Malaria Starts with Me [a continent-wide campaign to eliminate malaria], begun by Senegal, is about communities; it is ensuring that trash is cleaned up, etc. I think the zero malaria starts with me is a good starting point.  But I agree that if we want to address malaria and really beat it, it is a belt and braces approach, we shouldn’t be throwing out any interventions without a thorough assessment.

HP-Watch: What about R&D costs, a subject in the news recently.  Do you have any assessment of the costs to bring a new or adapted drug to market?

MMV and partners have implemented a series of platforms to gather data to feed into a tool to allow unbiased prioritization of optimal drug combinations for further research.

Reddy: The overall costs for development of a malaria drug is about $US 100 million.  The fully loaded costs are probably in the region of $US 200 million. If we pay a dollar, the pharma pays a dollar plus in-kind contribution such as their facilities.  This is not including drug attrition. But since we have a strong system of pre-clinical assays, we can kill drugs pretty early.

Today, we have a strong network of SCID (severe combined immune deficiency) mice assays that allow you to test drug or drug combinations very quickly. [at a later stage] We can also run tests on healthy human volunteers infected with very small amounts of malaria parasites before it becomes clinical, you can treat them [with the experimental drug], and then you can treat them with the standard drugs, so that in a very, very controlled setting you can explore your drugs, are they going to work, and the likely dose you can use with patients. This keeps costs down and speeds things up.

HP-Watch: What challenges lie ahead, and do you see MMV continuing to address malaria only, or could there be other targets for your work?

Reddy: I think there is a real acknowledgement that it is not the current generation of leadership that will finish this job, and that includes me.  We need to be looking for that next generation of leadership and scientists. Much of that leadership is going to be coming from the malaria endemic countries.  So, our work on empowering needs to be rooted in the Malaria endemic countries.

MMV will be focusing on developing better treatments for pregnant women in the coming years

We will be looking more closely at groups such as pregnant women, who are disproportionately affected by malaria.  Yet in drug development programmes, pregnant women are classed as a vulnerable population, and therefore [in the traditional R&D mindset] you protect them from new drugs. [But that leads to us not having adequate drugs for women in pregnancy]. We are all realizing that we have been thinking about this in completely the wrong way, and so we need to see how we can get them included in studies so that they can benefit from new drugs earlier. We need to create a stronger programmatic stream [around malaria in women/pregnancy] if we are going to change things and move towards more equitable access.

Finally, new malaria combination drugs are going to become more and more important in order to avoid resistance.  So, we are launching a “malaria drug development catalyst” [initiative].  This is a unique way of bringing partners together at an earlier stage of development, to look at what drugs can be combined.

With out partners, we have already developed the technical tools, such as mouse assays and human volunteer studies, that allow us to perform tests in a consistent way. All partners can access the molecules, and the molecules can be put through the same assays, so that you can do an apples to apples comparison and see which molecules work best.

As with the assays, we want to create a common way of doing assessments and common agreements with the different companies and partners, so that it is easier for them to work with us and together. This is becoming very important now because we have a number of new drugs coming up through the pipeline. So, it is one of those perfect moments in time when everything comes together, and this is a way of formalizing and accelerating things.

 

This story is part of a series supported by MMV on malaria innovation.___________________________________

About David Reddy: Prior to joining MMV, in 2010, Reddy was a Vice President at Roche Pharmaceuticals, in Basel, Switzerland. With 20 years of management experience in the healthcare industry includes: successful leadership of drug development teams; licensing and alliance management; market analytics and business planning; product and disease area management; and interfacing with Governments, NGOs and patient advocacy groups in priority disease areas including HIV/AIDS and pandemic influenza. He has a doctorate in Cellular and Molecular Biology from the University of Auckland, New Zealand and completed a Post-Doctoral fellowship in molecular neurobiology at the Friedrich-Miescher Institute in Basel Switzerland.

 

Image Credits: Anna Wang/MMV, Novartis, Ben Moldenhauer/MMV, NIAID, NIH, MMV, Elizabeth Poll/MMV.

In a move fraught with international political overtones, Italy’s new Minister of Health is moving to replace the Director General of the Italian Drug Agency (AIFA), Dr Luca Li Bassi, who was the key architect of the May World Health Assembly (WHA) resolution supporting greater price transparency in medicines markets, Health Policy Watch has learned.

The potential replacement of Li Bassi, a seasoned career public health professional, comes only a year after he was selected to fill the top civil service position at AIFA in an international, juried competition.

Luca Li Bassi holding Italy’s placard at the 72nd World Health Assembly with other lead co-sponsors of the WHA Transparency Resolution.

The move against Li Bassi has stirred protest among civil society drug access groups, which this week sent an open letter to the new Italian Health Minister, Dr Roberto Speranza asking him to reconsider the move.

The petition, signed by 21 organizations and about two dozen leading medicines access advocates, follows the publication last week on Italy’s Ministry of Health’s website of a call for applications for the position of director-general of AIFA (Agenzia Italiana del Farmaco).

The advertisement for a replacement for Li Bassi follows a September reshuffle in the Italian government whereby the left-wing Italian Article One party, in which Speranza is a leader, joined the Five Star party in the national government. As a reward, Article One received the health portfolio and Speranza was named as Health Minister. That portfolio had previously been held by Five Star Party member Giulia Grillo, who had taken over the job as Health Minister in 2018 under a Five Star party platform pledged to lower Italy’s soaring drug prices.

Grillo’s appointment of Li Bassi in October 2018, shortly after being appointed was a first step in that direction – and it set something of a precedent in Italy’s highly politicized government circles – due to the rigorous candidate selection process, overseen by an international panel of three public health experts. The process was even the focus of a Lancet opinion piece co-authored by Grillo, who admitted it was “quite unusual for Italy” but cited it as evidence that she and her government were committed to making policy choices anchored in “scientific-based methods”.

Luca Li Bassi in a recent interview on Italian national TV, Rai3

“We will apply the same methods, based on international reputation and meritocracy, that have worked well for AIFA and CSS for all future decisions concerning the leadership roles in the health system,” Grillo declared in the Lancet article published in August 2019.  Only a month later, following the government reshuffle, Grillo was out of a job.

In the intervening year that Li Bassi has held the post, he has rapidly made a name for Italy and himself in global health circles – initiating the unprecedented WHA proposal on the drug transparency resolution in February 2018, and then steering it to approval in the May WHA.  Li Bassi was widely credited for helping member states reach “common ground” in what  Angola’s Health Minister Silvia Paula Valentim Lutucuta described as “one of the most complex and polarising issues in 21st century global health.” Lutucuta chaired the WHA Committee A, which oversaw the WHA negotiations on the price transparency resolution.

But following September’s replacement of Grillo by Speranza in the government reshuffle, Li Bassi’s days now may be numbered, his supporters fear. Ironically, Speranza comes from an ardently left-wing party that would presumably be sympathetic to the price transparency agenda.  But that, informed observers remark, has apparently not made him immune to the time-worn traditions of patronage politics, including political appointments for key civil service posts.

Public notice for expressions of interest for the post of Director General of the Italian Drug Agency – AIFA
Protest By Civil Society Leaders Over Italian Move

In the civil society letter of protest to Speranza over Li Bassi’s possible replacement, the AIFA director was lauded for his role in “overcoming enormous opposition from vested interests” to see the May WHA resolution on “Improving the transparency of markets for medicines, vaccines, and other health products” approved.

“It is difficult to convey how great a challenge it was to get the WHA to consider, let alone approve a resolution dealing with transparency, given the longstanding drift towards greater secrecy and less transparency in every aspect of the development and pricing of medicines,” the signatories said.

“His expertise, commitment, compassion, diplomatic skills and tirelessness were critical to the adoption of the resolution,” the signatories noted. “It is very rare to see a senior government official do so much in such a short time to raise awareness across the global community of the need to change course on issues fundamental to – and perceived as contrary to –  the interests of the largest pharmaceutical companies in the world.

The groups also pointed to Li Bassi’s previous record with other UN agencies, non-profits and global health groups, such as the Global Fund to Fight AIDS, TB and Malaria, where he helped pioneer a transparent drug procurement system.

“Many of us worked with Dr Li Bassi during his earlier efforts to provide access to affordable drugs for the treatment of HIV in developing countries. His work in establishing the Global Price Reporting Mechanism (GPRM) at The Global Fund has been recognised as an example of the value and feasibility of implementing transparency policies in the pharmaceutical sector,” the letter stated.

Under Li Bassi, AIFA had been expected to help lead a group of technical experts from the so-called Valletta Group of countries to take forward some of the key outcomes of the WHA drug transparency resolution into a dialogue with the European Commission’s Employment, Social Policy, Health and Consumer Affairs Council. The aim was to develop framework legislation for European countries to voluntarily band together share price data and bargain collectively with industry on pharma prices.

Should Li Bassi be moved out and a leadership vacuum created, the plans of the Valletta group may be delayed, observers have said.

Leadership on CAR-T Therapies and & Locally-supported Research

In addition to the work pioneering the WHA drug transparency resolution, Li Bassi has also been setting precedents in Italy on the support and promotion of local cutting-edge research, leading to more affordable, cell and gene therapies, colleagues told Health Policy Watch.

He persuaded the Ministry of Health to establish a national public project, investing 60 million Euros to create Italian hospital-based production facilities for CAR-T cells.  The initiative should help keep the cost of the therapies down as use of the new gene therapies to fight cancer expands.

Li Bassi also created an innovative initiative with the pharmaceutical companies Gilead and Novartis, which hold patents on CART-T treatments for lymphoma and leukaemia, to reimburse the companies in accordance with the survival rates of the patients who get the therapies – keeping treatment costs down while incentivizing therapies that prolong life expectancy.   Through another initiative, AIFA and the Ministry are investing public funds in home-grown Italian research into CART-T therapies for other conditions, particularly for children.

“In addition to his work on transparency, Dr Li Bassi is one of the leading exponents of strategies to make new technologies, such as cell and gene therapies, more affordable,” notes the civil society letter to the minister. ”To this end, his effort to empower Italian research institutions to develop new CAR-T therapies within the public health system, is extremely important not only for Italy, but also as a progressive example for other countries.

“He has reached out to the leading scientific, technical and legal experts to advance this work, and has done so at a very critical moment, given the emerging regulatory, legal and reimbursement regimes that are only now being tested. Italy is one of the few countries to undertake pro-active assessments of possible ways forward in these areas, and this is largely the result of Dr Li Bassi’s willingness to challenge the status quo and to prioritize the public interest.”

 

Beatrice Marone contributed to this article.

Image Credits: Rai3, HP-Watch/E Fletcher, Italian Ministry of Health.

As a cholera outbreak inches closer to Sudan’s capital city of Khartoum, the Sudanese Ministry of Health and the World Health Organization are scaling up the response. Two cholera cases were confirmed in the district of Khartoum State on October 19. As of Monday, November 3, the Ministry of Health had reported 332  suspected cases of cholera since 28 August when the first case was detected.

While the recent cases have been mostly concentrated in Blue Nile and Sennar States, officials are concerned that if the current outbreak of the often fatal diarrhoeal disease spreads more widely in Khartoum State and from there, to the very densely populated, urban areas of the capital city, it would have an even more serious impact, particularly on children.

“The risk of cholera spreading is very real. If not properly managed, this could have potentially serious consequences. More than eight million people live in Khartoum State, where the public health system is impacted by the economic crisis, recent flooding, and ongoing outbreaks of infectious diseases,” said Naeema Al Gasseer, WHO Representative in Sudan, in a press release.

A health worker monitors the cholera vaccination campaign in Sennar.

Together with the Ministry of Health, WHO has conducted initial risk mapping in Khartoum State to identify which areas are more likely to be at increased risk. This will allow for more informed planning to ensure that vulnerable areas, such as Sharq Elnil and Ombada localities, are better prepared to respond. Two cholera treatment centers are being set up in Ombada and Bahri localities. So far, WHO has delivered cholera medicines and supplies to treat 400 severely dehydrated patients, as well as 500 rapid diagnostic tests, which can be used for screening suspected cases in health facilities. Some 1.6 million people are also to be vaccinated in Blue Nile and Sennar States as part of the response.

Some 271 health staff and paramedics have been trained in cholera detection and management with support from Doctors Without Borders/Médecins Sans Frontières (MSF) and WHO. The Ministry of Health and WHO are working with more than 1700 male and female health promoters and volunteers to raise awareness of cholera, as well as provide education on hygiene practices and environmental health in communities affected or at risk.

“A key aspect of preventing and controlling cholera is how well at-risk communities are able to protect themselves by drinking safe water, properly handling food, avoiding defecation in open areas, hand-washing, and knowing what to do when they see the first signs of infection,” said Al Gasseer.

 

Image Credits: Twitter: @WHOSudan.

A coalition of over 40 personalities – from doctors and economists to actors and health access activists – released an open letter Tuesday calling on the French Prime Minister Edouard Philippe and the Minister of Health Agnès Buzyn to support a series of amendments to the French Social Security Budget Bill for 2020 providing for greater transparency around the selection and pricing of drugs purchased for the national health system. The bill, which provides the framework for public health system funding, will be going before the French Senate next week, and drug pricing amendments were previously blocked by the Minister of Health in a presentation of the bill to the National Assembly on October 24th.

“The government’s negative review of these amendments is incomprehensible and politically untenable,” states the petition. Noted French academics, doctors, and cultural figures such as composer Bertrand Burgalat; writer Edouard Louis; economist Thomas Piketty, anthropologist Didier Fassin; and Academy of Medicine member and medical school faculty Alfred Spira, have all signed on to the letter to the Minister of Health and the Prime Minister.

The strongly-worded statement goes on to call the rejection of the price transparency measures a “denial of the French commitment made to the World Health Organization,” referring to France’s vote in favor of the landmark price transparency resolution passed at the 72nd World Health Assembly in May. While political leaders in other European countries such as Malta and Italy have been pushing the transparency agenda, civil society actors such as l’Observatoire Transparence Médicaments (OTM) have been driving the conversation around pricing transparency in France.

The proposed amendments contained in Article 28 of the budget proposal, would provide for the systematic publication of data on prices paid by the public health system for bulk medicine purchases; more detailed patent information, as well as data on public contributions to R&D costs.  The amendments would also give the government more leeway to use the threat of “compulsory licensing” –  to produce a generic version of patented drugs – as a bargaining tool in negotiations with pharmaceutical suppliers, Pauline Londeix of OTM told Health Policy Watch. The amendments were proposed by OTM and presented by Members of Parliament of the left-wing “La France Insoumise” Party to the National Assembly two weeks ago – but were shot down at the first reading of the bill by the Minister of Health.

French Health Minister Agnès Buzyn at the National Assembly on October 24th

“We are all in favor, of course, of a very regular review of the price of medicines. This is a goal we share. But it seems to me that the method proposed to reach it does not correspond to the reality of the facts,” said Buzyn in her negative opinion of Article 28. Buzyn explained that she thought the proposed amendments, such as one clause that requires all drug prices to be reviewed at a minimum every 5 years, would actually “lead to deviant practices” and lengthen the time between price reductions for drugs.

Buzyn claimed that in more than “half the cases” CEPS, the body in charge of negotiating drug prices, actually renegotiates prices in more frequent intervals than 5 years.

Still, the Senate meeting next week will present another opportunity for the transparency amendments to be included in the final version of the budget bill.

There is “a possibility” that the transparency amendments will be accepted at that meeting, before the bill is sent back to the National Assembly for a second and final review by that legislative body before it is adopted, Londeix told Health Policy Watch. “We hope that the Senate will support [the amendments].”

Delhi declared a public health emergency as air pollution levels soared on Friday, while Chief Minister Arvind Kejriwal said that the mega-city had “turned into a gas chamber”.

According to official government monitoring stations, levels of tiny PM10 air pollution particles had risen as high as 20 times WHO Air Quality Guideline levels in parts of the city over recent days. As of Friday evening, concentrations of the small particles, among the most health hazardous pollutants, were averaging 300-500 micrograms per cubic meter of air – or 6-10 times the WHO 24-hour guideline of 50.

Air pollution levels at 10 p.m. Friday night near Delhi national stadium, showing the combined data of three government monitoring networks, CPCB, DPCC and SAFAR

To cope with the emergency, the Delhi Government launched an unprecedented mass distribution of some 5 million masks to school children, banned construction, cancelled school until Tuesday and placed sharp limits on vehicle travel with an “odd-even” scheme permitting private vehicles to travel only on alternate days, as per the digits of their license plate.

“In the interest of protecting our children, it has been decided to keep all the schools – Government, Government-aided, and Private – in the National Capital Territory of Delhi closed until November 5th 2019,” said the Office of the Deputy Chief Minister in a decree published on Twitter.

Kejriwal blamed the increase in “stubble burning” in neighboring regions of Punjab and Haryana for Delhi’s recent spike in air pollution levels. The practice of burning leftover straw after grains are harvested is a rapid method for farmers to clear their fields, but also sends huge plumes of smoke and biomass pollution into the air, spreading for hundreds of kilometers.

“Delhi has turned into a gas chamber due to smoke from crop burning in neighbouring states,” said the minister on his Twitter feed. “It is very important that we protect ourselves from this toxic air. Through pvt & govt schools, we have started distributing 50 lakh [5 million] masks today I urge all Delhiites to use them whenever needed.”

But scientists and civil society activists maintained that no single source can be blamed for the city’s chronic air pollution problems, which peak in the early winter every year. Rather, a combination of urban and rural sources create a perfect storm of pollution that hovers over the city and the wider region. These also include pollution from domestic wood/biomass stoves; unfiltered smokestack emissions from Delhi area power plants; urban waste incineration; construction dust; the rampant use of polluting two-stroke engines in two-wheeler vehicles; as well as the seasonal “Diwali” festival of lights – where setting off firecrackers is a traditional ritual.

(left-right) Delhi sky on Sept 27, Delhi sky on Nov 1, Kejriwal distributes masks to school children in air pollution emergency

“We know that the air pollution comes from at least 8-10 sources.  We want the government to address all of these and not just cherry pick,” said Jyoti Pande Lavakare an activist journalist who runs the organization CareForAir.org and is completing a book “Breathing Here is Injurious To Your Health” to be published early next year.

She said that her organization had grave misgivings about the mask distribution scheme – whether the masks would in fact have adequate air pollution filters, and whether they would really reach 5 million people. On top of that, unless masks are properly fitted they won’t work at all, even as a stopgap measure – and for many children the masks will just be too large.

“Masks are not a solution,” said Lavakare. “And they may give you a false sense of security.  Masks are more of a visual. I am for masks because they make an invisible problem visible; they are an immediate necessity, but only if they fit well. And people who have asthma will feel suffocated if they wear a mask. The only real thing to do in an emergency is to stay indoors and keep respiration rates low.”

However, she added that Delhi’s chronic air pollution issues, which peak annually in November and December, required more than “short-term band-aid measures”, adding that leadership from the very top of the political spectrum was needed.

“I want the prime minister [Narendra Modi] to actually lead this issue; currently it is actually rudderless and leaderless. You cannot have a prime minister who is talking about clean India without talking about clean air.  And yet he has been strangely silent on this issue.  In no forum has he talked about air pollution,” she observed, noting that each air pollution source has a longstanding history of failure behind it.

For example, a Ministry of Environment, Forestry and Climate Change decision to install modern pollution filters on Delhi area power plants by 2017, potentially reducing average air pollution levels by about 30% in northern India, has been delayed for over two years by the Ministry of Power and could remain stalled until 2020 if the latter Ministry has its way. Three-wheeler vehicles, auto rickshaws, which provide much of the Delhi’s public transport, still run on heavily polluting two-stroke engines. And regional pollution from crop-burning has intensified as local varieties of nutrient-rich food crops were gradually replaced by rice, produced mainly for export and sucking up scarce water resources, says Lavakare.

Lavakare is, however, more hopeful that the debate about air pollution is growing stronger and public opinion more informed about the multiple health risks air pollution creates – which according to WHO range from spikes in hospital admissions and death rates during air pollution emergencies to stunted childhood lung development, reduced long-term life expectancy and higher premature mortality from stroke, heart disease, lung cancer, and respiratory disease as a result of chronic air pollution exposures. Recent evidence has also pointed to serious air pollution impacts on the brain development of infants and young children.

“When we started to build awareness three years ago, we were told by top government officials that it was a rich person’s problem. The point they were missing was that it is a bigger social inequity for the disenfranchised and the homeless people who don’t have the privilege of having masks, air purifiers and four walls to keep the pollution out.

“Now, the government can no longer say this is just a rich person’s problem. It’s clear that it is everyone’s problem.  And the Indian media is finally fully supportive,” said Lavakare. “No one [politician] cares if it it really is creating toxic impacts on health, but people do care if it gets them votes. And at least that is a start. But we need a tipping point – like the film ‘Under the Dome‘ which got China to do something.”

It was clear that after the fifth day without sunlight, average Delhi residents were crying for change.

“No air circulation. Eyes burn. Breathing is difficult. Can’t even go out for a walk. Sick!” commented one commentator on Twitter.

One Indian parliamentary member, former cricketeer Gautam Gambhir critiqued the high-level response and urged Kejriwal to check how many construction sites are complying with the new regulations on the ground.

A high profile, India-Bangladesh cricket match planned for Sunday provided a lightning rod for a lively debate over the air pollution emergency, with critics calling for the match to be postponed because of the irreversible health impacts exposure to such high air pollution levels can have, but sports authorities resisting.

UN Goodwill Ambassador and Indian actress Dia Mirza blasted the Board of Control for Cricket in India (BCCI) decision to continue hosting the India versus Bangladesh match on November 3rd, despite the dismal air quality.

“BCCI please stop hiding your head in the smog,” she tweeted. “This air harms players and the people that come to watch these games.”

One cricket commentator drolly observed that perhaps the BCCI’s decision to not cancel the match was strategic, saying that “Indian cricketers are better used to such bad air than any other cricketing nation.”

Indian players, used to playing in environments with poor air quality, will be able to better tolerate the ghastly air pollution levels and play better than athletes who are used to training in climates with lower levels of air pollution, he reasoned.

“India shall, through series openers scheduled in Delhi’s toxic air, introduce pulmonary disintegration to the game,” said Siddharth Monga in a piece for ESPN.

Grace Ren contributed reporting to this story.

Image Credits: www.aqicn.org, Arvind Kejriwal.

Cutting-edge health technologies – such as gene editing therapies for cancer – have the potential to save lives, and the international intellectual property system should be leveraged to drive innovation and bring those therapies to people who need them, said the leaders of global health, trade and intellectual property agencies at a Trilateral Symposium on Thursday.

The symposium, convened under the theme “Cutting-edge Health Technologies: Opportunities and Challenges,” is the eighth such open forum co-hosted by the World Health Organization (WHO), the World Trade Organization (WTO), and the World Intellectual Property Organization (WIPO) to foster collaboration around public health and intellectual property.

(left-right) Dr Tedros, Roberto Azevêdos, and Minelik Alemu Getahun.

“The essential insight is that while improving access to existing technologies remains an important priority, it will not suffice to meet future public health challenges,” said the WTO Director-General, Roberto Azevêdo, in his opening statement. He noted that advancements in new diagnostic tools, therapies, and prophylaxis treatments have greatly expanded the possibilities for treating and preventing certain diseases.

As an example, Azevêdo highlighted CAR-T (chimeric antigen receptor) cell therapy, a cutting-edge cancer treatment still under development. This form of cell therapy leverages advancements in gene editing by genetically altering natural white blood cells to attack cancerous cells. Public sector research institutions currently hold 40% of the patents in this area of medical research, while private firms hold 49%.

“How [the patent holders] choose to license these technologies will be an important factor in how therapies are rolled out in practice,” said Azêvedo.

The Director-General of the WHO, Dr Tedros Adhanom Ghebreyesus agreed, stating that “Advances in science and technology are opening up new horizons in public health that were considered science fiction not so very long ago… And yet we continue to live in a world marked by shocking inequality.”

Dr Tedros posed the question, “How do we harness the power of innovation to narrow inequalities, rather than widen them?”

“We must understand better the benefits, costs and limitations of mechanisms for incentivizing innovation and their impacts on the pricing of health products,” he added, reaffirming WHO’s commitment to Universal Health Coverage, including increasing access to medicines and vaccines.

The IP system also faces challenges as scientific advancements quickly move forward, WIPO Assistant Director-General Minelik Alemu Getahun said, noting that IP regulations must balance “incentivizing and rewarding innovation” while ensuring that knowledge to support “continued innovation” is shared.

“Today’s discussions will explore the landscape of cutting-edge health technologies and consider some of the opportunities and challenges of optimizing their use in a variety of settings. We should endeavour to make our discussions as accessible to the public as possible by elucidating concepts and providing clear, fact-based information related to these exciting and ever-evolving health technologies,” he said.

The three opening speakers set the stage for a broader technical discussion on the challenges and opportunities of cutting-edge health technologies. A morning plenary reviewed highlights of new medical innovations in biotechnology, information technology, and the application of big data to the medical sector. A second panel focused more on issues of access to new medical innovations, affordability and increasing costs for health care systems, along with the ethics of using patient data.

For more information, see the WTO press release.

Image Credits: WTO.

Non-communicable diseases (NCDs) such as cancer, heart disease and stroke, as well as road traffic injuries, are among the leading causes of death in cities – killing some 42 million people worldwide every year. A new report released by the World Health Organization shows how urban leaders can tackle these urban maladies through simple environmental design strategies and as well as food, tobacco and alcohol policy measures.

The report, The Power of Cities: Tackling Non-communicable Diseases and Road Traffic Injuries, suggests ten high-impact interventions for cities, based on WHO expertise as well as the experiences of 19 cities where the strategies have been tested in case-studies.

“Over half the world’s people live in cities, and the numbers are rising,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General in a press release about the initiative, released on the UN-designated World Cities Day.

“City leaders take decisions that impact on the health of billions, and for cities to thrive, everyone needs access to services that will improve their health – public transport, safe, clean and attractive outdoor spaces, healthy food, and, of course, affordable health services.”

The case-studies cover low-, middle- and high-income countries, with 15 of the 19 studies focusing on cities in developing countries, where 85% of premature adult NCD deaths and a whopping 93% of road traffic crashes occur. Currently, seven of the ten largest cities in the world are in developing countries, and 90% of future urban population growth will occur in low- and middle-income countries, the report notes.

The report’s stated goal is to share knowledge and best-case practices between city leaders and help them to “identify at least one area which could be changed for the better.”

“By replicating the most effective measures on a global scale, we can save millions of lives,” said WHO’s Global Ambassador for NCDs and injuries, and three-term New York City Mayor, Michael Bloomberg.

“We’re working to raise awareness among city leaders and policy makers about the real gains that can be achieved when effective programs are in place.”

High-Impact Interventions for NCDs and Road Traffic Safety
A man bikes in Fortaleza, a Brazilian city that implemented a bike-sharing scheme in 2014.

From anti-tobacco actions in Beijing and Bogor, Indonesia, to road safety initiatives in Accra, Ghana and Bangkok, a bike sharing scheme in Fortaleza, Brazil and actions to create more walkable streets that have reduced pedestrian deaths among older people in New York City by 16%, the report aims to share knowledge between urban policy planners.

Specifically, the report highlights ten key interventions that could reduce NCDs and road traffic accidents:

  • Monitor NCD risk factors – Conduct a population-based survey of behavioral risk factors for NCDs, such as tobacco use, alcohol consumption, dietary habits and physical activity.
  • Create a smoke-free city – Protect people from second-hand smoke through the introduction, passage and enforcement of legislation that makes all indoor public places 100% smoke-free.
  • Ban tobacco advertising – Ban all forms of direct and indirect tobacco advertising, promotion and sponsorship.
  • Reduce the consumption of sugar-sweetened beverages – Establish and implement policies to reduce sugar-sweetened beverage consumption, such as taxes on the production or sale of sugar-sweetened beverages.
  • Reduce salt consumption – Implement key components of the WHO SHAKE package for salt reduction in city communities, businesses, and institutions.
  • Create walkable, bikeable, and liveable streets – Improve pedestrian and bicycle networks and infrastructure across the city to ensure safe and equitable access to services, and to promote more walking and cycling for recreation and transport.
  • Clean the air – Reduce ambient air pollution through promotion of cleaner transport, municipal solid waste management, and controls on industrial emissions, and promote cleaner indoor air by improving access to cleaner fuels and technologies for cooking, heating and lighting.
  • Reduce drunk-driving – Increase enforcement of drunk driving laws
  • Manage speed – Establish lower speed limits and strengthen existing speed-limit enforcement.
  • Increase seatbelt and helmet use – Increase enforcement of seat-belt and motorcycle helmet use.

Many of the interventions are based on the WHO’s Best Buys for NCD Control that list policies that can not only help countries reduce the health impacts of NCDs, but also their economic costs.  It is estimated that implementing such measures could help low- and middle-income countries save some US$350 billion by 2030.

The report was produced as part of a Bloomberg Philanthropies-funded joint initiative the Partnership for Healthy Cities, involving WHO and the global health NGO Vital Strategies. The partners are now working with city leaders to implement variations of the ten interventions in 54 participating cities around the world.

The initiatives covered some 216 million people in urban areas with at least one intervention to help reduce the risk of NCDs or road traffic accidents in 2017. On a larger scale, the city-level initiatives are contributing to fulfilling countries’ commitments to the Sustainable Development Goals – to reduce premature deaths from NCDs by a third by 2030, and to halving road traffic deaths and injuries by 2020.

“With most of the world living in cities, bold action by urban leaders has greater potential to improve lives than ever before… Increasingly, we see cities rising to societies’ biggest challenges – from climate change and road safety, to obesity and tobacco use. They are engines of change, able to move quickly to implement life-changing policies that affect great numbers of people,” said José Luis Castro, president and chief executive officer at Vital Strategies, in a statement on World Cities Day.

Along with the report, WHO has provided a number of technical resources to city leaders to help guide policy-making for NCDs and road traffic safety – for more information, see the report webpage.

Image Credits: WHO/Vital Strategies, WHO/The Power of Cities: Tackling NCDs and Road Traffic Injuries.

Berlin, Germany – A “public interest R&D” model can bring effective treatments for neglected diseases to patients at comparatively low cost, through a collaborative, access-oriented development process.

The model is outlined in the new report 15 Years of Needs-Driven Innovation for Access, by Drugs for Neglected Disease Initiative (DNDi), released Wednesday.

The model etches an alternative formula to conventional for-profit R&D systems, highlighting both successes and challenges that are faced in developing treatments for over a dozen diseases, such as sleeping sickness and Chagas disease, that affect some of the poorest and hardest to reach populations in the world.

A healthcare provider screens people for African sleeping sickness, a disease for which DNDi developed the first all-oral treatment, fexinidazole.

“After 15 years I think I am proudest of the model. It was originally just an idea but now it is a reality,” Bernard Pécoul, executive director of DNDi, said during a day-long symposium reflecting on DNDi’s research experiences held on the occasion of the organization’s 15-year anniversary. He said that the report takes “30 pages to describe 15 years of a story.”

According to the report, the organization has delivered eight field-adapted and affordable treatments for diseases as varied as paediatric HIV, sleeping sickness, and Chagas disease to date, and expects seven or eight more treatments by 2023. Currently, DNDi has more than forty R&D projects across seven disease areas, as well as more than 20 new compounds – known as “new chemical entities (NCEs) – in early stages of development.

The report attributes DNDi’s success to an innovative funding, partnership and access model, among other factors. By partnering with academia and the private sector, for instance, the organization is able to access existing research databases holding information about millions of compounds, and has screened 4 million to date. It is through such screening that the organization has been able to identify compounds that had potential to treat serious diseases, but had simply been ignored or discarded in the R&D pipeline because their profit potential was low.

At the same time, the organization’s access policies ensure that the collaborations with industry are negotiated up front, in a way that any consequent drugs produced will be made widely available at affordable prices– e.g. through open licensing or generic formulations that are not limited by patent requirements to pay expensive royalties.

In addition, some 60% of DNDi’s funding still comes from public sources such as government grants, and the organization attempts to maintain financial independence by “not having one donor with more than a 25 percent share of contributions,” said Pécoul.

In terms of collaborations, DNDi’s model has stressed working in countries that are affected by the diseases that it is tackling, the report notes.

The organization is working with over 180 partners in more than 40 countries, with at least one third of the collaborating institutions based in lower-middle income countries. These partnerships include five new disease-specific clinical research platforms based in Africa and Latin America. Through these partnerships, the organization runs an average of 20 clinical trials enrolling over 2500 patients total at any given time.

“Public Interest R&D” – How Does This Model Work?

The report summarizes six elements identified as key to the success of DNDi’s alternative, non-profit R&D model. These include positioning the product development partnership as: needs-driven; independent; collaborative, open and transparent; globally networked; access oriented; and “transformative.”

In keeping with its public-interest mission, the organization publishes its financial data on an annual basis to remain “open and transparent,” informing the debate around R&D costs.

Adjusting for attrition, DNDi estimates that it can develop and register new combinations or new formulations of existing treatments for €4-32 million, and an entirely new chemical entity for €60-190 million. Conventional industry estimates are for a US$2.6 billion cost to bring a new drug to market. Although the numbers are not directly comparable because DNDi’s work is focused on a few key infectious diseases and industry estimates also include the “opportunity costs” of capital investments, they provide an order of magnitude comparison of how non-profit R&D can be cost-effective, DNDi experts say.

Public and private contributions pay for the cost of R&D up front, allowing the organization to focus on developing new drugs based on patient needs rather than the need to recoup R&D costs.

R&D is guided by the use of public-interest “target product profiles,” which include concerns around access and affordability from the outset.

For example, until 2009, the standard treatment for African sleeping sickness caused by a parasite transmitted by the tsetse fly, was an arsenic-based intravenous treatment that was so toxic that it used to kill one in twenty patients – but the disease itself was almost invariably fatal without treatment.

Sleeping sickness affects some of the poorest and hardest-to-reach populations in the world, with over 80% of cases occurring in the most remote regions of the Democratic Republic of the Congo. In the traditional treatment, highly trained staff had to deliver as series of infusions over a period of weeks, following diagnosis via a painful lumbar puncture.

The first DNDi breakthrough came in 2009, when it developed a less toxic and more effective oral nifurtimox-intravenous eflornithine combination therapy (NECT).

That replaced the arsenic-based Melarsoprol. However, the treatment still requires 21 days of hospitalization, or massive equipment if deployed in a field clinic, as well as highly trained staff who had to deliver a series of infusions, following diagnosis via a painful lumbar puncture.

In response to the need for a yet more adaptable and field-friendly treatment, DNDi identified fexinidazole out of a Sanofi library of chemicals as having potential efficacy against sleeping sickness.

In November 2018, the drug was approved by the European Medicines Agency as first oral medication for sleeping sickness, and it was registered in DRC just a month later, thanks to an EMA collaboration with African regulatory authorities, also facilitated by DNDi.

The 3C’s:  Collaboration, Coordination & Cooperation

The story of sleeping sickness illustrates how a collaborative, open and transparent process, driven by a global network of partners, has been key to the DNDi treatment breakthroughs.

Fexinidazole ultimately was developed in partnership with more than 15 organizations representing government, private industry, and civil society, while Sanofi remained the main pharmaceutical development partner. Clinical trials for fexinidazole were conducted in the DRC and Central African Republic.

“DNDi owes its successes to collaborations with a large global network of over 180 partners from the pharmaceutical industry, academia, health ministries, other NGOs, treatment providers, and patients and their communities, as well as our donors,” said Pécoul in a press release.

“We are the conductors of a ‘virtual orchestra’, and the eight new treatments we have delivered in the past 15 years would not exist without the commitment and shared vision of our partners and donors.”

One of the latest brainchilds of DNDi is not a product – it’s a new organization dedicated to tackling the growing threat of antimicrobial resistance, the Global Antibiotic Research and Development Partnership (GARDP).

Initially housed within DNDi after its inception in 2016, GARDP launched as an independent organization in July and is now running four R&D programmes for drug-resistance infections, applying the DNDi drug development model to the neglected area of developing new and improved antibiotic treatments.

Image Credits: Xavier Vahed/DNDi, DNDi/15 Years of Needs-Driven Innovation for Access.