The recent approval by the US Food & Drug Administration (FDA) of benznidazole to treat Chagas disease in children highlights some of the frequently overlooked barriers to treating neglected tropical diseases (NTDs) outside their traditional settings. While long recognized as a serious issue in Latin America, it is only recently that Chagas has received much attention in the United States and Canada. In the United States it is now estimated that the disease affects over 300,000 people and there is evidence of local transmission in areas where the insect vector, the kissing bug, is present. In Canada, cases of transmission from mother to child and via blood products have been reported in addition to those in migrant populations from endemic countries.
Nevertheless, although benznidazole is listed as a WHO Essential Medicine for treatment of Chagas disease, it has never previously been approved for use in the United States or Canada. In the United States this meant it was eligible for a Priority Review Voucher (PRV) as a new treatment for a tropical disease, even though it has been in use elsewhere since the 1970s. These vouchers, which grant the holder priority in the review of another drug, are also transferable, making them a valuable commodity. Consequently, for those concerned about affordable access to NTD treatment, it comes as a relief that the first recipient of FDA approval is a partnership involving the Drugs for Neglected Diseases Initiative that promises not only to keep the consumer price down but also channel part of the proceeds (from transferring the PRV) back into promoting access. The likely alternative was a company explicitly targeting benznidazole as an easy way to profit from monopolizing an old drug, while collecting a PRV in the process.
This was the strategy attempted by KaloBios Pharmaceuticals (now Humanigen), which fittingly began their own benznidazole project under the helm of then-CEO Martin Shkreli. Shkreli had by then already become the poster boy for pharmaceutical profiteering by jacking up the price of another off-patent WHO Essential Medicine (pyrimethamine for toxoplasmosis) by over 5000% overnight. This price hike was possible because the market was small enough that there was only a single approved supplier; whoever controlled that supply had a monopoly. Pyrimethamine, although the most famous example, is not the only decades-old WHO Essential Medicine to undergo a dramatic price increase in the United States under similar circumstances in recent years. Hopefully benznidazole has now been spared this fate.
Unfortunately for Americans facing high pharmaceutical prices, the oft-proposed idea of allowing Americans to purchase their medicines from Canada is not the right prescription for NTDs for one simple reason: key drugs for NTDs are not approved for sale on the Canadian market. This includes not only benznidazole, but some of the most basic drugs in the global health toolkit. For instance, neither albendazole nor ivermectin, both crucial antiparasitics, is approved for human use in Canada (except, in the latter case, in a topical cream for treatment of rosacea). Ivermectin was one of two drugs whose importance was recognized with the Nobel Prize in Medicine in 2015 (the other, the antimalarial artemisinin, is not approved in Canada either).
While small markets for some essential medicines in the United States led to single source production ripe for exploitation, in Canada—with a little over 1/10th the population of the United States—drug companies have shown little interest in garnering marketing approval in the first place. After all, Canada is not a country one associates with tropical disease. Nonetheless, one in five Canadians was born abroad, and many others travel widely for business and pleasure. Furthermore, even decidedly un-tropical Canada is not bereft of NTDs like scabies, Echinococcosis, and other parasites best treated with these drugs. Consequently, there is a clear need for access to medicines for NTDs both now and in the future.
Even though the Government of Canada has supported the use of essential medicines for NTDs abroad, at home many are available only through the Special Access Programme (SAP). Designed for access to new and experimental drugs of unproven utility, not decades-old essential medicines, the SAP frequently results in delays in access, if the treatment is obtained at all. The SAP is particularly frustrating in the case of conditions like cutaneous larva migrans which, while highly distressing to the patient, do not meet the SAP’s standards of being serious or life-threatening. While drug compounding is an option in some cases, it is not an ideal solution. And although Canada has recently enacted a new mechanism making it easier to import unapproved treatments that have received approval in the United States, European Union, or Switzerland, this pathway is designed for large-scale emergencies such as ‘flu pandemics or the opioid overdose crisis, not for a small but steady stream of individual cases of NTDs.
Thus, while recent successes in improving access to treatment for NTDs worldwide should be applauded, ongoing obstacles in countries like Canada and the United States should not be ignored. NTDs exert a comparatively minor burden in these countries, but the medicines in question are no less essential to those patients who require treatment. There is no doubt the world needs more and better tools to tackle NTDs, but addressing self-imposed barriers to making existing tools affordable and accessible for those who need them, wherever in the world they may be, is a human rights obligation and a step that should not be neglected.
Adam Houston is a PhD candidate in law at the University of Ottawa, Canada.