Phase III malaria vaccine: don't count your eggs before they hatch

Two events prompted this post. First, several people have asked me if the malaria vaccine they heard about in the news will eliminate malaria. Second, the GSK CEO Andrew Witty discussed pricing strategies (5% profit above the yet unknown production costs) for this vaccine, called RTS,S, at a recent talk. Wait – pricing? We don’t even know how well the vaccine works! The press touts RTS,S as the world’s most advanced malaria vaccine. This is true in someways, it is in phase III trials which is the stage immediately preceding licensure and market sales. In and of itself this is a terrific achievement. However, advanced does not equal effective, and effective does not equal useful. Concerns about vaccine storage, dosing, delivery, and cost still remain.

The available RTS,S phase II results (previously discussed here) were far from spectacular, but efficacy was not the main endpoint of these trials. At that stage the investigators were focused on other aspects of a vaccine such as safety, dose finding, and immune response. The larger phase III study should answer the question of efficacy, but which efficacy are we talking about? Is it the efficacy in reducing all clinical malaria vs severe manifestations vs parasitemia or in children vs adults or for the first vs the fifth year after the receipt of the vaccine? Likely several different endpoints will be presented, and there will be disagreements about which one is meaningful for a particular country. If I were a betting man my guess is poor efficacy and low utility for public health, but I hope I’m wrong.

On a related note – will GSK receive a priority review voucher if RTS,S is licensed? The priority review voucher program was created in 2007 as an market-based incentive for companies to develop drugs and vaccines for neglected diseases. It allows a company to decrease the standard FDA review time, by 6-12 months, for another treatment of their choice. The economic value from the accelerated approval of a blockbuster drug is estimated at $100-500 million. Could the prospect of a voucher influence GSK’s decision to seek FDA approval? There is also the issue of the GSK-owned novel adjuvant (an immune response booster) used with RTS,S. What is the licensing process for adjuvants? I suspect that if an adjuvant has been used in a licensed vaccine, it can then be sold for use in any existing or new vaccine. Or at the least other companies would be more likely to risk using that adjuvant during vaccine development. If so, GSK may have another incentive to license RTS,S. From the talk of their CEO they already seem certain that a vaccine of any form will be pushed through the FDA.

PS GSK’s contribution and committment to the malaria vaccine began in 1987 and is commendable. Other contributors should also be noted. The Walter Reed Research Institute (run by the US Army) conducted much of the key early research. The Gates Foundation, through their Malaria Vaccine Initiative, has funded much of the vaccine’s development costs since 2001.

PPS The first voucher granted under the priority review program was for malaria. Novartis received one for its antimalarial drug Co-artem (artemether+lumefantrine). In this case the drug was not novel, available for almost a decade now, but was only recently licensed in the US making it eligible.

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