The market for treatments of malaria - which kills over one million people a year -- is of almost no commercial value: Although patients seek over 300 million treatments a year, and perhaps as many suffer without treatment, few legitimate drug companies make any money from the business. It is for this reason that one would typically be excited that new drugs to treat the disease, produced by Chinese firm Guilin Pharmaceutical, and Indian firm Ipca Laboratories have been approved by the World Health Organization. But recent history suggests that caution is very much in order.
The two largest companies still engaged in any meaningful way in malaria research are Novartis and Sanofi Aventis. Novartis signed an agreement with the World Health Organization in May 2001 to provide Coartem at cost to patients in malarial countries. Coartem, the first artemisin combination therapy (ACT), is the best anti-malarial since chloroquine, which was once the gold standard, effective for 50 years saving millions of lives. But with resistance to chloroquine accelerating in the past decade, alternatives like Coartem have become essential.
As with HIV, another fast-changing pathogen, it makes sense to give drugs in combination. This forces the pathogen (in this case, the malaria parasite) to simultaneously develop resistance to all combined medicines at once in order to survive—statistically unlikely, at least assuming drugs were stored and administered correctly.
The problem with combination therapies is that they are necessarily more expensive, since they involve at least two drugs, and ideally have gone through entirely new development to allow both drugs to work correctly in a single formulated pill.
Now that more funding has been dedicated to the prevention and treatment of malaria with the inception of the Global Fund to Fight AIDS TB and Malaria, and President Bush's Malaria Initiative, demand has soared for new drugs. But Coartem is still the only ACT on the market that has been tested by a high-quality regulatory agency - both the Swiss and EU agencies, which are equivalent to US Food and Drug Administration. Last year Novartis provided 62 million treatments—all at cost, as per their agreement.
Like Novartis, Sanofi has a long tradition working on malaria and has developed a new ACT, Coarsucam. Some evidence suggests that the malaria parasite may have developed resistance to one of the drugs, amodiaquine, in the Coarsucam combination. But the drug is potentially very useful, adding to the arsenal of weapons that health departments in malaria countries can use against the disease.
But unlike Coartem, Coarsucam has not yet passed approval by a western drug safety agency or even the WHO's historically dubious prequalification process. Three years ago, the WHO approved 18 anti-HIV medicines produced by several Indian companies, which were subsequently withdrawn because they could not be demonstrated to work as well as the branded drugs they copied. Coarsucam must be tested properly to ensure it is truly effective.
With so much funding flooding the market and so many counterfeit products in the market, it is important to have some level of certainty about supply. In the past two weeks the Government of Kenya announced that it was demanding a recall of large amounts of fake anti-malarials. The legitimate Chinese manufacturer Holley-Cotec is having to take part in the recall because a counterfeiter, possibly also Chinese, has been making fake versions of its drugs.
So far funders have been slack about ensuring quality. The Global Fund has spent many millions on medicines of uncertain quality. From data I have seen 56% (5 of 9) of purchase orders sent out by the Global Fund went to suppliers neither approved by WHO or a stringent agency. Privately some Global Fund staffers tell me they are unhappy that their board approved the purchase of these drugs, apparently to deny Novartis a monopoly of supply.
Given these facts it is with both hope, but mainly concern, that WHO has prequalified three of the copycat medicines that the Global Fund is already buying. Guilin is producing amodiaquine and a version of Coarsucam (amodiaquine plus artesunate). And Ipca is producing artesunate. It is surprising that WHO, which has fought against approving monotherapies, would approve single chemicals. One of the treatments already has resistance problems in certain countries while the other is the best product on the market but should only be used in dual therapy to prevent resistance. Guilin is capable of producing good chemicals but it is a shame that it has chosen to ask for prequalification for anything using amodiaquine. Ipca is more of an unknown quantity, but given a recent Wall Street Journal story about corruption in Indian drug supplies to the World Bank, one should be skeptical.
Having more high quality suppliers in the market would be great. But it will be interesting to see whether the WHO's testing is up to the mark, or whether these products will have to be withdrawn at a later date, if it is found that they're substandard - as happened with HIV medicines before.
WHO's approval of these copy drugs provides vindication to the Global Fund since it was already buying them. I imagine that Novartis will also be a little relieved since it has been obliged to satisfy a surging demand for ACTs, something that was very poorly predicted by the international health community over the past few years. Since ACTs take at least 14 months to produce due to the growth cycle of the sweet wormwood plant from which the product is derived, which in turn requires agreements with farmers, inaccurate forecasts mean over- or under-supply of ACTs. And given the attendant bad press companies would expect from undersupplying the market, both Sanofi and Novartis have overproduced drugs in previous years, leading to product destruction and millions in losses.
It will be interesting to see whether Guilin and Ipca will be able to provide consistent as well as safe supply of the product. Somehow I doubt it. The WHO has a difficult job to do and is woefully under-funded to do it. Until its budget is increased in order to test drugs properly and forecast their demand with any accuracy, Novartis will continue to bear the brunt of its agreement with WHO. It is enough to make them want to tear it up.
Roger Bate is a Resident Fellow of the American Enterprise Institute.