GSK's clinical trial for a malaria vaccine could consolidate its position as a front-runner in neglected disease research

Last November, GlaxoSmithKline topped the Access to Medicine Index for the third year running. Complimented for their equitable pricing policy in emerging markets and a pro-access approach to licensing and patents, the ranking marked a turnaround for a company which, little more than a decade ago, was public enemy number one.

In the late 1990s, GSK - along with other big brand producers - fought the South African government’s efforts to allow generic drug companies to distribute cheap copies of Aids medicines to deal with the country’s epidemic. The saga cast a long, lingering shadow over Big Pharma’s public reputation in developing countries.

Today, in contrast, the British pharmaceutical giant appears to be a front-runner. “GSK has a long-term sustainable access strategy, evidenced by their strong performance in all the areas we measure,” says Tara Prasad, senior researcher at the Access to Medicine Foundation.

“They have maintained leadership due to their ability to innovate”.

While drug donations and reinvestment of profits are part of GSK’s access strategy, it will be the innovation pipeline which consolidates their position as a corporate force for good in Africa. Most notable is a malaria candidate vaccine, called ‘RTS,S’, currently in a Phase 3 trial across seven African countries (Kenya, Tanzania, Mozambique, Malawi, Gabon, Ghana and Burkina Faso). Results so far show a reduction in clinical and severe malaria by about half in children aged 5-17 months, and one-third fewer episodes in infants (6-12 weeks of age).

“There were doubts among some that a large, complex Phase III trial like this could be successfully conducted in Africa. But the African research centres have done an excellent job,” says David Kaslow, director of the PATH Malaria Vaccines Initiative, a partner in the trial.

RTS,S - which is backed by funding from the Bill and Melinda Gates Foundation - still has some way to go. Lower effectiveness among 6-12 week olds is a worry given the vulnerability of this age group to malaria-related fatality. But the importance of the investigation goes beyond the vaccine. A well-run clinical trial in Africa could encourage other companies to follow, and reassure skeptics that such investigations can be held successfully in developing countries. “It will provide a proof of concept that you can conduct trials of this magnitude in a continent that many have feared to venture into,” says Dr Allan Pamba, GSK’s director of public engagement and access initiatives.

The history of clinical trials in developing countries is a troubled one, from controversial investigations into the contraceptive pill in 1950s Puerto Rico to Pfizer’s infamous 1996 meningitis treatment trial in Nigeria, during which several children died or acquired disabilities.

Motives for conducting trials in emerging economies range from the scientific appeal of ‘treatment naivety’ (lack of much prior drug use in participants from these countries makes it easier to isolate the effects of the candidate product) to lower costs.

Some practitioners worry that companies are seeking to evade regulation by moving to less developed countries. “One potential reason for testing an agent in a poorer country is that you don’t get hit by litigation so hard,” says Edwin Gale, emeritus professor of diabetic medicine at the University of Bristol. “If a person in Uganda is sick, no one is going to realise that what they are complaining of is because they are in a clinical trial”. And some companies are holding trials in bigger emerging markets to push products to doctors and populations rather than to advance medical knowledge - a process known as ‘seeding’ - says Professor Gale.

Tara Prasad says GSK’s clinical trial conduct in developing countries is superior to its competitors, and common criticisms directed at pharma companies running trials in developing countries do not seem to apply to GSK’s malaria investigation. It is not a ‘seeding’ attempt since trials for diseases like malaria have to be conducted where the disease burden is highest. “Testing a malaria vaccine in a malarial area is clearly appropriate, and this product is potentially a major contribution to global health,” says Ben Goldacre, author of Bad Pharma. Seeding tends to be a bigger issue in large emerging markets where the commercial landscape is more attractive.

The motivations are not about cost-cutting or looser regulation, since Africa is proving an expensive and burdensome place to conduct the work - from getting electricity to trial site hospitals and building up staff capacity to securing import permits, transporting high-end equipment and getting samples tested on time.

“Initially everyone thought running such trials in Africa would be cheaper due to low labour costs,” says Dr Salim Abdulla, an investigator for RTS,S in Tanzania. “But this is replaced by the high cost of maintaining the infrastructure and putting in place the systems required to be able to do studies properly”.

Far from being a lax environment, the rules and regulations covering the seven countries are hard to navigate. While the EU has a single regulatory agency, as does the US, Africa’s regulatory environment is fragmented. “Regulatory agencies are poorly financed, and slow in making reviews,” says Dr Pamba. In the case of Nigeria, the regulator even demands that trials collect data from two regions because the population of the north is “different” to that in the south. “In my perspective, it is one people,” he says. “It’s a requirement which, if they go easy on it, will make it much easier to conduct trials. You can’t develop a product in Africa without involving a country like Nigeria”.

Then there are the ethics in a trial involving nearly 16,000 children.

Gathering informed consent from participants and their families may be harder, not easier. Many patients have a ‘God complex’ with their physician and “do not understand the idea that the physician needs their approval...If you are conducting a clinical trial you have to go to great pains to explain that they can say ‘no’,” says Dr Pamba. All told, the risks are considerable. “If anything went wrong with a clinical trial you have a huge reputational risk in that environment. You have to go an extra mile to ensure that things are done properly,” Dr Pamba says.