Market incentives

Because not all desired clinical trials can be funded, the global health community is tapping the stimulus power of market-based "pull" mechanisms such as Advance Market Commitments (AMCs) that guarantee prices for new vaccines and drugs with low profit potential in the US or Europe. This approach is being used to spur production of artemisinin-based combination therapies (ACTs) that are effective, but require subsidies to be affordable in developing counties.

The Global Fund to Fight AIDS, Tuberculosis, and Malaria recently launched the Affordable Medicines Facility—malaria (AMFm) to make ACTs available in Africa and Asia at a nominal cost. The AMFm will subsidize the purchase of fixed-dose combination ACTs or combinations in coblistered packages approved by FDA or European authorities or on the World Health Organization's (WHO) prequalified drug list. By expanding the market for these effective, high-quality therapies such as Novartis's (Basel) Coartem (artemether-lumefantrine) and sanofi aventis's ASAQ (artesunate-amodiaquine), the program aims to drive older, ineffective products out of the market.

FDA's priority-review voucher program offers another inducement for manufacturers to support R&D on neglected disease treatments. The program provides a voucher to sponsors who seek approval of a treatment for one of 16 neglected tropical diseases. The voucher is good for a future priority, six-month review (instead of the usual 10 months or more), which should be highly lucrative to any company seeking market approval for a new medicine with large sales potential.

The first voucher was recently awarded to Novartis in conjunction with the approval of the antimalarial Coartem in the US. The move drew criticism because the program is supposed to reward companies for developing brand-new treatments, and Coartem has been available for more than a decade around the world. The Novartis application got the program going, however, while FDA develops guidance and weighs whether to expand the list of tropical diseases that qualify for review vouchers.

The search for new vaccines

The holy grail for global health initiatives is to spur R&D on new vaccines that prevent lethal infections, and public–private partnerships are making progress in this area. PATH's Malaria Vaccine Initiative is launching Phase III trials of a malaria vaccine developed by GSK, and the Aeras Global TB Vaccine Foundation has several candidates in early clinical trials. Rotavirus vaccines recently received a strong push from WHO, which in June recommended including this preventive in national immunization programs for infants and children.

Vaccine development also is strong in industrialized nations, as new preventives for human papillomavirus, rotavirus, and shingles have hit the market. FDA anticipates a slew of license applications in coming months, and they could be overwhelming if they coincide with filings for the new pandemic H1N1 vaccine that is being tested and produced as fast as possible. The US expects to spend some $8 billion for testing and purchase of 100 million doses of the flu vaccine from GSK, Novartis, Sanofi Pasteur (Lyon), Astra-Zeneca's (London) MedImmune, and CSL (Victoria, Australia). Billions more will come from the United Kingdom, France, Germany, and other nations.

FDA and industry face several challenges in developing and producing the new pandemic vaccine, as discussed at a July meeting of FDA's Vaccines and Related Biological Products Advisory Committee. To speed the preventive to patients, FDA is allowing licensed manufacturers to file manufacturing supplements for a strain change, similar to what vaccine makers do each year for new seasonal flu vaccines. Because the H1N1 vaccine is a slightly different single-strain vaccine, though, companies must conduct clinical trials to ensure safety and to determine the necessary dose strength and number for effectiveness. Another question is whether the swine-flu vaccine should be administered separately or with a seasonal flu shot, which manufacturers already have produced in large quantities.

In addition, the National Institutes of Health (NIH) is conducting clinical trials to test dosing options for various age groups, as well as the need to mix the new vaccine with an adjuvant to achieve the desired immune response. If adjuvant is needed, FDA plans to use its emergency use authority to expedite access to what would be a new vaccine.

Even if all the test results are positive, it's not clear how quickly industry will produce the millions of doses needed. Companies experienced difficulties cultivating antigen from the available H1N1 strains, but yields began to rise last month, bolstering hopes for initial supplies in September. MedImmune reported great success in producing bulk quantities of its FluMist vaccine, which is made from live virus, but doesn't have enough nasal spray devices to deliver the inhaled product.