Drug companies return to the fray

The old cheap antimalarials have an increasingly limited shelf life swissinfo.ch

New ways of funding drug development have galvanised the search for malaria treatments.

For the last 40 years, most pharmaceutical companies have neglected malaria because like other tropical diseases it offers little return on investment.

Between 1975 and 1999 only four of almost 1,400 new drugs developed worldwide were antimalarials.

Now, however, industrial expertise combined with funding from government and private sources has seen researchers trying to identify new, more effective drugs.

“The tide has definitely turned,” says Chris Hentschel, chief executive of Geneva-based Medicines for Malaria Venture (MMV).

MMV was set up in 1999 and arranges public-private partnerships with the aim of producing one new antimalarial drug every five years and making them available in poor countries.

Given that most projects fail over the 15-year period it takes to produce a drug, it’s estimated that it costs $500 million for every new treatment brought to market.

“For malaria, the only real commercial market is the travellers market which is maybe worth $200-300 million a year,” says Hentschel.

“That sounds like quite a lot of money but in pharmaceutical terms, it is below the radar screen. It’s too little really to stimulate new R&D.”

Ancient remedy

Artemesinin-based antimalarials are now seen as the most effective medicines to treat drug-resistant malaria.

The medication is derived from the plant artemesia annua, used for centuries in China as a remedy against various forms of fever.

In 1972, Chinese scientists discovered that the extract contains substances which possess strong antimalarial activity.

Artemesinin and its derivatives act rapidly reducing the number of parasites in the blood to very small numbers within 48 hours. But to completely get rid of infections, the treatment has to be followed for a week.

Combined with more slowly eliminated drugs, such as mefloquine or lumefantrine, artemesinin can cure in three days.

Coartem produced by Novartis is a combination of artemether and lumefantrine formulated together in a single tablet.

Artequin produced by Mepha has the separate components artesunate and mefloquine in a single blister in a pack.

Generics

In the field of antimalarials, Mepha carries out its own clinical research to develop new compounds, but the company is best known for manufacturing generic versions of drugs.

Generics contain the same active ingredient as the original product, guarantee identical quality but can be up to 50 per cent cheaper.

The company also tries to improve upon the original. Advantages might include easier administration – once instead of three times a day – better absorption, reduction of side effects and a longer shelf life.

Plasmotrim Rectocaps, a suppository form of one of the company’s artemesinin-based antimalarial drugs, can be used to treat severe cases where patients are often unconscious or incapable of swallowing tablets.

“Mothers can easily administer it to young children,” says Nathalie Cambon, head of Mepha’s medical department. “You also avoid the need for an injection and consequently the risk of infection.”

In addition it is thermo stable – another advantage in endemic malaria countries where temperatures easily exceed 30 degrees Celsius throughout the year.

Meanwhile, Novartis is planning to develop a paediatric formulation of Coartem in cooperation with MMV because of the difficulty children have in swallowing tablets.

Side effects

Two Roche products have been widely used in the prophylactic and treatment market. In 1971, Roche launched Fansidar, a combination product of sulfadoxine and pyrimethamine, for the treatment of chloroquine resistant malaria.

Today, generic versions are still widely used in many areas of Africa, Latin America and Asia where chloroquine resistance has developed.

Lariam, launched 17 years ago, is Roche’s brand name for the anti-malarial drug mefloquine, which is also marketed under the trade name Mephaquin, manufactured by Mepha.

More than 25 million people worldwide have successfully used mefloquine for treating and preventing malaria.

Although a minority of patients report severe side effects, many health experts believe that the risk of taking the drug is far outweighed by the potentially lethal chance of contracting malaria.

“It is known that mefloquine has neuro-psychiatric side effects,” comments Theo Leuenberger, international business leader for anti-infectives at Roche.

“Most of the time, these are mild. We think three to five per cent really do not tolerate the drug and should get an alternative.”

Halving deaths

Besides MMV, two other major international programmes based in Geneva have been launched in the past five years to raise the profile of malaria control and to tackle issues of funding, research coordination, and public and private cooperation,

The World Health Organization’s Roll Back Malaria campaign aims to halve malaria deaths by 2010.

The Global fund to fight Aids, Tuberculosis and Malaria works to attract new resources to fight these three infectious diseases.

All represent a new infusion of political interest and financial commitment.

“The difficulty in the long run will be to maintain that level of engagement not just from the private sector but also public sector donors,” says Robert Ridley of the WHO’s tropical disease research programme.

“I believe progress has been made over the last five years, I am optimistic that it can be maintained but it probably needs to go up several orders of magnitude if the impact is really to be felt in the countries affected by the disease.

“The future success of the Global Fund is critical. They are talking about a $10 billion budget. They are getting about ten per cent of that. You probably need several billion dollars a year to make an impact on malaria.”

swissinfo, Vincent Landon

Key facts

Quinine appeared in the 17th century and was used to treat and prevent malaria until 1942.
Chloroquine was first used in the 1940s but resistance is now widespread.
SP, also known by its Roche brand name Fansidar, is still widely used.
Mefloquine marketed by Roche (Lariam) and Mepha (Mephaquin) is a common prophylactic.
Travellers also use Malarone, produced by GlaxoSmithKline.
Artemesinin-based compounds include Coartem made by Novartis and Mepha’s Artequin.