To be or not to be exclusive: the sutezolid story

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.¹ 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.² Horrifically, only one of two people treated for multidrug resistant (MDR) tuberculosis are cured,¹ 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 showed favourable pharmacokinetic properties, efficacy against drug-resistant strains of tuberculosis, and low toxicity in rat models. ³

After lying undeveloped for several years in the hands of Pfizer and others, there is a new window of opportunity for the drug. Sequella, a pharmaceutical corporation, acquired the licence for the development and commercialisation of sutezolid from Pfizer in 2011. However, Johns Hopkins University still owns some key pieces of the intellectual property.

Despite more than 2 years of discussions with public health advocates and civil society, it seems that Johns Hopkins plans to licence exclusively its intellectual property around sutezolid to bring this compound to market. Unfortunately, an exclusive licensing plan would not only inhibit development of a MDR tuberculosis regimen but could also result in a highly priced and inaccessible product. Two recent drugs provide prescient examples of the need for non-exclusive licensing.

Bedaquiline, approved by the US Food and Drug Administration (FDA) in 2012, was recently added to a Médecins Sans Frontières treatment regimen in Armenia. Here, the sputum clearance rate at 6 months' follow-up⁴ was 84% in patients with drug resistance,⁴ which compares favourably with the usual 50% average successful treatment rate for MDR tuberculosis.¹

Unfortunately, in March, 2015, it was estimated that only 1000 patients had received bedaquiline.⁵ Janssen, the company that makes the drug, charges US$900 and $3000 for a course of this drug in low-income and middle-income countries, respectively, and $30 000 in the USA. These prices have left poorly funded health departments desperate, unable to scale-up treatment programmes. Furthermore in March, 2015, Janssen had registered the drug in only 21 countries. The high prices for bedaquiline are especially infuriating given that Janssen received a priority review voucher from the FDA and that the drug was fast-tracked through FDA approval.⁶ This price barrier has been temporarily removed with a donation plan, but programmes like this one are often unsustainable and countries not included in the plan still face high prices.

If the story of bedaquiline's release to the market is worrying, then the approach of Otsuko, the company that produces delamanid, a drug for the treatment of MDR tuberculosis, has been even worse. Approved by the European and Japanese regulatory agencies in 2014, delamanid has filed registration in only Europe, Japan, and South Korea. The drug is marketed in the UK and Germany only, at a price of $28 000 for a 6-month course of treatment in the UK. More importantly, patients in low-income and middle-income countries have no access to this drug.

Fortunately there is a charted path in another direction. The UNITAID Medicines Patent Pool (MPP) has been a model for best practice in the area of sharing intellectual property to improve drug access. Since July, 2010, UNITAID has sought voluntary licences for technologies related to HIV, and as of December, 2015, 12 antiretrovirals have been placed in the patent pool for licensing. More than 50 sublicensing agreements have been completed to allow rapid production of generic drug and lower prices.⁷ The model delinks the price of drug development from the eventual price a patient pays by allowing generic drug companies to compete. In November, 2015, the MPP expanded its mandate to include voluntary licensing for hepatitis C and tuberculosis medicines. This non-exclusive licensing model can be easily borrowed and applied by academic institutions like Johns Hopkins University.

Johns Hopkins School of Public Health turns 100 years old in 2016. I am proud of the institution and its legacy over the past century. But a centennial celebration must be as much about the promise of the future as it is about the achievements of the past. Insisting on non-exclusive licensing would be an unforgettable toast.

By Jane Andrews

I declare no competing interests.

References

1. WHO. Global Tuberculosis Report. http://www.who.int/tb/publications/global_report/gtbr15_main_text.pdf?ua=1; 2015. ((accessed Dec 21, 2015).)
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5. Médecins Sans Frontièrs, MS. A breath of hope for drug-resistant TB. http://www.msf.org/article/video-breath-hope-drug-resistant-tb. (accessed Dec 15, 2015).
6. Médecins Sans Frontières. Ready, set, slow down: new and promising DR-TB drugs are grabbing headlines but not reaching patients. http://www.msf.org/sites/msf.org/files/msf_issuebrief_drtb_readysetslowdown.pdf. (accessed Dec 21, 2015).
7. Medicines Patent Pool. About the medicines patent pool. http://www.medicinespatentpool.org/about/. (accessed Sept 24, 2015).

Source: The Lancet Global Health