Pf looks at how the pharmaceutical industry is working with WHO to transform the developing world by defeating neglected diseases such as sleeping sickness and river blindness.

In January 2012, the World Health Organisation (WHO) launched a roadmap to defeat 10 key neglected tropical diseases, with support from 13 major pharmaceutical companies. The campaign targets diseases that are widespread only in the developing world and form major barriers to the economic development of the affected countries. The companies pledged to work in partnership with WHO, governments and health and finance organisations to strengthen their drug donation programmes, support drug distribution and implementation, and increase R&D in this disease area.  

Trojan horses
Most neglected tropical diseases (NTDs) are carried by parasites (such as tsetse flies) or are parasites (such as flatworms), which makes them difficult to treat as parasites are well adapted to the biology of the host. The parasite often acts as a ‘Trojan horse’ introducing disease into the human body. While preventative measures such as sanitation are important for controlling infection, only effective drug treatment can strike at the lethal team of parasite and micro-organism. The challenge is not only to develop effective drugs, bu to ensure they reach the populations affected by the disease.

In the ‘London Declaration on Neglected Tropical Diseases’, WHO and 13 drug companies committed to these objectives for 2020: to eradicate guinea worm disease; make progress towards eliminating lymphatic filariasis, blinding trachoma, sleeping sickness and leprosy; and achieve control of schistosomiasis, river blindness, Chagas disease, visceral leishmaniasis, and soil-transmitted helminthes. The companies involved are Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Gilead, GSK, Johnson & Johnson, Merck KGaA, Merck Sharp & Dohme (MSD), Novartis, Pfizer and Sanofi.

Margaret Chan, Director General of WHO, said: “The efforts of WHO, researchers, partners, and the contributions of industry have changed the face of NTDs. These ancient diseases are now being brought to their knees with stunning speed. I am confident almost all of these diseases can be eliminated or controlled by the end of this decade.” For some of the world’s poorest nations, that means an end to a crippling burden of endemic disease.

As a Sanofi video commented, NTDs are neglected because the populations they affect are neglected. For the pharma industry, offering drug donation, training and education to defeat these diseases is an opportunity to put down roots in important future markets, as well as boosting the industry’s public image through concrete achievements. Despite the current global economic crisis, funding for neglected disease R&D has increased significantly since 2007. Corporate social responsibility is a key aspect of any global drug company’s strategy – especially for companies based in Europe
and the US, where reputation can be a difficult issue.

In May 2012, Dr Margaret Chan commented on work to fight schistosomiasis in Africa: “These Cinderella diseases, long ignored and underappreciated, are a rags-to-riches story. We can blanket this part of the world with medicines that rid every schoolchild of worms and eggs, parasites that interfere with their learning, impair cognitive development, and compromise their nutritional status.” Such achievements, which depend on the pharmaceutical industry, are of historic importance on the world stage.

River blindness
Onchocerciasis (river blindness) causes an estimated 270,000 people each year in Africa and elsewhere to lose their sight. Its biological audit trail is complex: a nematode worm enters the body through the bite of a blackfly; the worms spread through the body, carrying symbiotic bacteria; when the worms die, the bacteria trigger the human immune system, causing severe itching and damaging eye tissue. Some 37 million people are infected with river blindness.

The most successful treatment is MSD’s Mectizan (ivermectin), an oral medication that kills the parasite in its larval stage. On 11 October 2012 (World Sight Day), MSD celebrated 25 years of its programme to donate Mectizan for treatment of river blindness. Through this programme, progress has been made towards eliminating the disease in Nigeria, Uganda, Senegal, Mali and Sudan. MSD is committed to maintaining drug donations until the disease is eliminated.

The Mectizan Donation Programme has influenced the development of other initiatives to fight NDTs in two ways: its multi-sector partnership model and its use of community-directed intervention (CDI). Stakeholders working with MSD to build the programme include WHO, the World Bank, governments, NGOs and communities. The CDI strategy, whereby communities plan their own means of delivering treatment, has enabled Mectizan to be delivered to 75 million people in Africa each year.

Former US President Jimmy Carter commented: “In Africa, where it was once thought river blindness could only be controlled, strides are being made to completely eliminate the disease from a number of countries. Thanks to MSD, the commitment of endemic communities, and strong partnerships, we can now envision a world someday free of river blindness.”

A leading distributor of Mectizan in Africa is Sightsavers, an NGO committed to preventing blindness. Simon Bush, Sightsavers’ Director for NTDs, told Pf: “Sightsavers will, through its support to river blindness programmes in Africa, treat over 25 million people this year as well as playing our part in supporting a network of about one million community-directed distributors.

“We have also the proof of the elimination of transmission of the disease in Kaduna state in Nigeria, which shows that elimination of the disease can be achieved in Africa through treatment with Mectizan alone.” 
The contribution of MSD has been “vital”, Bush said: “Sightsavers would not be able to support the elimination of river blindness and blinding trachoma if it were not for the drug donation programmes. We would not have been able to go to scale.” The supply chain reaching from a major pharmaceutical company to a network of community-directed distributors, reaching through society and across the world, is expected to eliminate transmission of the disease in the targeted countries by 2021.

Blood fluke
Schistosomiasis (blood fluke) is a parasitic flatworm infestation. The larvae enter the body from fresh water sources, mature in the liver and travel through the blood vessels, laying eggs that trigger destructive immune reactions. The disease is estimated to affect 200 million people in Africa and to cause 200,000 deaths each year.

The only medicine with which all forms of schistosomiasis can be treated is Cesol (praziquantel) from Merck Serono (a division of Merck KGaA). In 2007, the company committed to donate 200 million Cesol tablets to WHO for distribution to school-age children primarily in Africa, and to support an awareness programme in schools. In January 2012, Merck Serono doubled its annual donation of tablets to 50 million, to be maintained until the disease is eliminated. It has committed to work with partners to develop a pre-school version of the drug.

Seven million children were treated with Cesol in 2012, bringing the total to 28 million. At the end of November, Merck Serono symbolically donated the 100 millionth Cesol table to WHO, and announced a new programme to distribute the medicine throughout Kenya.

The company’s CEO, Stefan Oschmann, said: “Merck Serono is committed to more effectively fighting neglected tropical diseases.” He added that partnership is the essence of the campaign: “The closer we co-ordinate the donation activities, research and development of new drugs, as well as the supply and distribution of drugs with each other, the more effectively we’ll be able to fight these diseases.”

Sleeping sickness
Trypanosomiasis (sleeping sickness) is one of the tropical world’s most feared diseases. It is spread by the bite of the tsetse fly and affects the brain, causing sleepiness, coma and death. Almost always fatal if untreated, sleeping sickness may be the real basis of the ‘zombie’ myth. But now, according to Dr Margaret Chan, “the stage is set for the elimination of sleeping sickness, a prospect that was unthinkable a decade ago”. For over ten years, Sanofi has worked with WHO to provide drugs and develop treatment protocols for the disease via the campaign ‘Human African Trypanosomiasis – Not Neglected by Sanofi’.

In 2011, Sanofi renewed its commitment to fighting sleeping sickness through a $25m donation, extending its partnership with WHO by another five years. The company donates three of the five drugs used to treat the disease. In January 2012, Sanofi announced a global partnership with Eisai and the Bill & Melinda Gates Foundation to eliminate five NTDs including sleeping sickness and lymphatic filariasis. In July, it noted that the sleeping sickness treatment programme had saved 170,000 lives and reduced the number of new cases from 30,000 in 2001 to 6,500 in 2011. By 2020, WHO has said, Africa may be clear of the disease.

Sanofi’s video from Chad illustrates the methods used to implement treatment. By funding mobile medical teams working in towns and villages, the campaign has brought daily drug therapy to people unable to travel long distances to the city hospitals. Seeing the effects of treatment within the community encourages other patients to be treated there. Sanofi is committed to providing the drugs and supporting their implementation until sleeping sickness is eliminated.

Most of the leading pharmaceutical companies are improving access to their medicines in the developing world, a new report shows.

The Access to Medicine Index identifies GSK, J&J and Sanofi as the companies doing most to make their drugs available and affordable in poorer countries.

Better pricing deals and development of drugs for neglected diseases are among the areas of company activity praised by the report, but the management of drug trials in developing companies is criticised.

GSK, which topped the Index in 2010, remains in front though its overall rating is only slightly higher. J&J and Sanofi have significantly improved their ratings.

The major Japanese firms are bottom of the league, as well as being absent from such initiatives as the WHO campaign to fight neglected tropical diseases.

In its third year, the Netherlands-based Index notes that companies are showing better internal organisation in relation to drug access issues.

Of the 20 largest pharma companies, 17 have improved access to their drugs in the developing world since 2010: they are developing more relevant drugs and doing more to facilitate patient access to them.

In particular, more companies are using tiered pricing schemes to make products more affordable for certain countries or population groups – most notably Gilead, whose HIV drugs are used worldwide.

However, the Index states that companies could do more to support generic versions of their drugs and adapt drug packaging to local needs.

It also notes that the outsourcing of clinical trials to Contract Research Organisations lacks transparency and control, with only four companies (GSK, Sanofi, Eisai and Merck & Co.) saying they enforce ethical codes.

Wim Leereveld, CEO of the Index, said: “Access to medicine is a multi-faceted challenge and the pharmaceutical industry has a critical role. While it has made strides in many areas, companies that have sector-leading practices also show us there is more the industry can contribute.”

Uptake of the MMR vaccine in infants has passed 90% in England for the first time since the 1998 research paper questioning its safety.

The exposure of Andrew Wakefield’s study as not only flawed but based on fake data has led to renewed confidence in the MMR vaccine.

Rising incidence of measles has also helped to boost uptake of the vaccine, which is now protecting 91.6% of children under the age of two – an increase of 2.1% from 2011.

However, this still falls below the WHO target of 95%, which experts consider sufficient to prevent outbreaks of measles.

The incidence of measles in England and Wales in the first half of this year (964 cases) was nearly twice that in the first half of 2011 (497 cases), with significant outbreaks in Merseyside and Sussex.

The MMR (measles, mumps, rubella) vaccine protects against the three viral infections. It is thought to give 99% protection against measles.

Wakefield’s 1998 article claimed to prove a link between the MMR vaccine and autism. It took 12 years for flaws in his research to be uncovered, and a further year before it was exposed as fraudulent.

“Today’s report marks a significant point in the continued rise of MMR coverage since it hit a low in 2003–04,” said Tim Straughan, Chief Executive of the Health and Social Care Information Centre. “For the first time in 14 years, nine out of 10 children in England have had the MMR vaccine before they turn two.”

Dr Helen Bedford of UCL Institute of Child Health commented: “It is good news that parents have regained their confidence in this highly effective vaccine. However, some teenagers and children have never caught up with missed vaccines and remain at risk of these potentially harmful infections.”

India’s Health Ministry has ordered states to stop licensing branded medicines, aiming to restrict the country’s drug market to generics.

From now, pharmaceutical companies applying for a licence to market or manufacture drugs in India will have to submit the generic name – over which they have no exclusivity.

The policy is a response to a threefold increase in healthcare costs over a decade, and will radically affect the pharmaceutical industry’s footprint in one of the world’s fastest-growing markets.

According to the Drug Controller General, Dr G.N. Singh, “We want to gradually move towards a future where we will not issue any brand or trade names. We are going all out to push generic drugs solely for the benefit of the public.”

The Government is also seeking to increase the availability of free medicines through public health clinics, reducing the private sector market – which currently dominates drug purchasing in India.

A WHO study found that 20–40% of India’s public health clinics had adequate stocks of generic medicines, compared to 40–60% of private clinics.

About 72% of healthcare expenditure in India is money paid by individual patients for drugs.

Healthcare expenditure tripled between 1994 and 2006, while individual income rose only by two-thirds.

Drug prices rose by 40% between 1996 and 2006, with increased drug consumption having more economic impact than price rises.

Health decision-makers representing European nations have adopted a new World Health Organization (WHO) policy for sustainable public health.

The Health 2020 roadmap, which focuses on disease prevention and reducing health inequalities, was endorsed by the WHO Regional Committee for Europe during its meeting in Malta.

The policy targets major health challenges affecting Europe, including the increasing health inequalities within and between countries, the ongoing pressure on public service budgets, and the growing incidence of chronic diseases.

Zsuzsanna Jakab, WHO Regional Director for Europe, said: “There is a lot of action in different countries, by governments, donors, the private sector, nongovernmental organisations and other groups, but we need these different players to pool their knowledge and work together.

“So many factors affect health, and health has an impact on so many areas of our lives, that progress on public health can only come from whole-of-society and whole-of-government efforts.”

Representatives of the health systems of 30 countries voted to support the new pan-European policy.

A new health strategy from the World Health Organization (WHO) challenges European governments to improve public health capacities and services.

European governments have been invited to adopt the Health 2020 framework, which focuses on reducing health inequalities and improving governance for health.

With its emphasis on the direct role of government in improving healthcare provision, Health 2020 conflicts with the current direction of NHS reform.

Launching the strategy, WHO noted that while life expectancy has increased in Europe over the past 20 years, health inequalities have also increased.

The strategy identifies four public health priorities:

• Investing in health through a life course approach and empowering people.

• Tackling the major health challenges of non-communicable and communicable diseases.

• Strengthening people-centred health systems, public health capacity, and emergency preparedness, surveillance and response.

• Creating resilient communities and supportive environments.

While noting the limitations imposed by the current economic climate, WHO argued that “good health is essential for economic and social development”.

Health 2020 proposes a number of headline targets for European member states by 2020: reducing premature death and health inequalities, increasing life expectancy and ensuring universal healthcare coverage.

Writing in the BMJ, health policy expert David J. Hunter noted that “political will in many [EU] member states is currently against state investment and intervention to improve health and to tackle its social determinants”.

European leaders will shortly be invited to endorse the WHO action plan for strengthening public health capacities and services.

The experienced Dr David Heymann has been appointed Acting Chair of Public Health England.

He will join the new public body with immediate effect and work with Duncan Selbie, the Chief Executive Designate, to ensure its effective establishment.

Health Secretary Andrew Lansley said it was a “welcome and timely appointment”.

Dr Heymann will fill the role until a permanent appointment is made in the autumn.

Public Health England will be responsible for protecting and improving the public’s health through the provision of health protection services. It aims to provide expert public health advice and professional support to local authorities, the NHS and the general public.

“I am delighted to be given this tremendous opportunity to play a role in the development of Public Health England,” said Dr Heymann. “In particular, my appointment as Acting Chair of Public Health England will enable me to work closely with Duncan Selbie to help assure continuity of service provision as we move through the transition period.”

The current Chairman of the Health Protection Agency (HPA) has a number of years experience working within healthcare. Prior to joining the HPA, he served in a number of senior roles at World Health Organization.

A host of pharmaceutical and biotechnology companies will join forces alongside public research organisations and scientific experts to address the rising threat from antibiotic resistance.

Companies including GSK, AstraZeneca, Janssen and Sanofi will partner in a new £180 million research programme to boost the discovery and development of new antibiotics.

Patrick Vallance, President, Pharmaceuticals R&D at GSK said the agreement “signals a new model of collaboration” to develop treatments to tackle infections such as MRSA.

NewDrugs4BadBugs is supported by the Innovative Medicines Initiative (IMI) – who will jointly fund the first project with contributions from the pharma and biotech companies involved.

The objective of the collaboration is to improve the underlying scientific understanding of antibiotic resistance and design and implement clinical trials that see novel drug candidates clinically developed.

Currently, the WHO describes the pipeline of future antibiotics to counter emerging resistant bacteria as “virtually dry”.

Antibiotic resistance is increasingly becoming a worldwide health threat with new ‘superbugs’ evolving around the globe.

However, despite the urgent need for effective counteraction, research has diminished over the past 15 years with few companies remaining active in this area due to difficulties in finding new agents and regulatory complexities.

Martin Mackay, President, R&D, at AstraZeneca commented: “It is time to tackle this issue in a different way, sharing information and expertise among public and private partners – collaboration of this type is critical if we are to speed up the discovery of these medicines to improve patient health.”

The World Health Organization has the support of 13 major pharmaceutical companies in developing a co-ordinated strategy to eliminate or control 10 key neglected tropical diseases, including sleeping sickness and river blindness, by 2020.

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Roche is withholding key clinical data which may question the safety and effectiveness of its anti-influenza drug Tamiflu (oseltamivir), a BMJ investigation claims.

The Journal is still waiting to receive full access to key clinical data about how well the drug works, two years after Roche promised to release it.

The investigation, published to coincide with a similar report from the Cochrane Collaboration, also questions the use of ghost writers in clinical trials and the different approaches taken by health regulators.

Tamiflu has become the main flu treatment in the UK and has been listed in the World Health Organization’s Essential Medicines.

A request by legitimate investigators from the Journal was made in 2009 to receive access, to which Roche agreed. However, despite repeated requests, the pharma company has yet to provide the data.

Roche, when questioned by investigators, admitted that some of the published papers surrounding Tamiflu had been ghost written. Concerns were also raised about the different approaches taken by regulators considering this data and the conflicting messages it created about the treatment’s effectiveness.

The BMJ found that the FDA chose not to review the largest clinical trial when considering the drug for approval and the US Centers for Disease Control and Prevention refer to trials which had been ghost written.

Meanwhile, the EMA only released a proportion of the clinical study reports to the Cochrane Collaboration after admitting it did not request the remainder of the information from Roche – despite being legally entitled to do so. It now says it will publish full reports for all products submitted for approval in the future; a move backed by the Journal.

“We hope very much that the EMA will indeed take this important step in making the full study reports available,” said Dr Fiona Godlee, BMJ Editor-in-Chief. “But we are still a long way away from having a full trial history for all drugs in clinical use. Public safety and the proper use of public money demands that we should stop at nothing less than this. In a globalised world, regulators should cooperate and pool their limited resources. Otherwise we will continue to waste money and risk people’s health on drugs that don’t work.”

Cochrane researchers aimed to test Roche’s claim that Tamiflu prevented complications and reduced the number of people who required hospitalisation with influenza. However, their investigation was hampered by a lack of supplied data by the pharma giant. It did obtain data from the EMA, but found inconsistencies with published reports and the possibility that the side-effects of the drug had been under-reported.

Questions were raised about the clinical effectiveness of the treatment. The Cochrane group, after evaluating the trial data it did obtain, claims Tamiflu appears to affect antibody production in patients – something Roche refutes. When asked by the BMJ, the manufacturer refused to explain precisely how Tamiflu works.

“Until more is known about the mode of action of neuraminidase inhibitors, health professionals, patients and other decision makers need to reflect on the findings of this review before making any decision about the use of the drug,” say the group.

The Collaboration also claims that Tamiflu’s ability to prevent the spread of influenza has not been demonstrated in trials – a statement which questions the move by governments around the globe to stockpile the drug in addition to the vaccine that has been developed since Tamiflu’s release.