smoothened Frustratingly in the past years the

Frustratingly, in the past 40 years the world has added only two new drugs to the arsenal against tuberculosis, the second most deadly infectious disease on the planet. The statistics are infuriating: more than 9 million people developed tuberculosis in 2013, and an estimated 44% of those in countries such as the Philippines, Thailand, and South Korea have resistance to at least one of the second-line agents for tuberculosis treatment. Horrifically, only one of two people treated for multidrug resistant (MDR) tuberculosis are cured, and the toxic 2-year treatment regimen involves thousands of pills and hundreds of injections. For extensively drug resistant tuberculosis (XDR-TB) the cure rate drops to 20%. With new agents like sutezolid being used in combination with other drugs, we might be on the brink of being able to save more lives with less toxicity. Sutezolid, originally U-100480, began development alongside linezolid in 1996. Even then it smoothened showed favourable pharmacokinetic properties, efficacy against drug-resistant strains of tuberculosis, and low toxicity in rat models.
Response from Johns Hopkins University At this stage, there are scant data on sutezolid\'s safety or efficacy in patients with tuberculosis. A series of clinical trials, which typically cost more than US$50 million, will be required to understand these issues and inform potential benefits versus potential risks to patients. Sutezolid\'s early stage of clinical development sets it apart from the in-market or late-stage clinical development HIV medicines targeted by the Medicines Patent Pool.
In (August, 2015), Tikki Pang and colleagues emphasise that “we must find the right balance between the roles of government and markets so that all those in need can access affordable medicine and health care“. Probably the biggest imbalance between role of government and market is in drug discovery and development. There is almost no way to finance large clinical trials of old, unpatentable drugs repurposed for treatment of deadly diseases. It has been the case for phase 3 clinical trials of paromomycin, an old antibiotic for visceral leishmaniasis, which were funded by the Bill & Melinda Gates Foundation, the WHO, and other institutions, but not by governments. At the same time, such clinical trials may lead to very efficient and low-cost drugs developed in the public interest. The cost of paromomycin is €4·19 for a 21 day course for a 35 kg patient. Recently, published results of a clinical trial of an old drug used in alcohol-aversion therapy, disulfiram, in patients with metastatic lung cancer. The drug is unpatentable, inexpensive, and widely affordable, but there is no financial interest in its further clinical development. The governments, especially those of rich countries, should systematically monitor positive side-effects of existing drugs and invest in their clinical development as non-profit drugs.
We thank Boris Cvet for his comments on our Article and agree with him that discovering new uses for old drugs offers great promise with regard to making treatments for neglected tropical diseases in low-income and middle-income countries more cost-effective and accessible. This is an important and neglected area. While we agree with Cvek that an imbalance exists in the role of governments and markets in investing in drug discovery and development, we propose that this is only one dimension of the problem. Broadly speaking, and with the large investments involved, we believe that most governments will neither have the resources, nor the political will, to invest in the clinical development of such drugs, and are therefore unlikely to make the necessary commitments. Instead, we suggest that governments can help facilitate the achievement of the desired right balance between the roles of government and markets through alternative but complementary and synergistic strategies. We propose four such strategies. First, governments can support the development of publicly accessible collections of existing drugs. Despite the promise that finding new uses for existing drugs is a proven shortcut to improve access, comprehensive collections of the nearly 10 000 drugs known to medicine does not exist. Government support for development of collections such as the Johns Hopkins Clinical Compound Library would go a long way to facilitating the rediscovery process. As suggested by Cvek, such a strategy will facilitate government-backed efforts to, as capsule put it, “systematically monitor positive side-effects of existing drugs”.