[Ip-health] Access to New TB medicines: The Sutezolid Story

Syed Ahmad drugsafetyconsultant at gmail.com
Mon Feb 1 07:25:59 PST 2016


Dear All,

The saga on access to new TB drugs continues. Thought the following open
access story on sutezolid by Dr. Jane Andrews of Universities Allied for
Essential Medicines and Tulane will be of interest to folks in this forum.

Best wishes,

Rizwan

Syed Rizwanuddin Ahmad, MD, MPH, FISPE, FCP
Pharmacovigilance Consultant with a Special Interest to Strengthen National
Medicines Regulatory Authorities in Resource-limited Countries
Ex-Consultant/Safety Reviewer, U.S. FDA (1998-2013)
Associate Professor (adjunct), Rutgers School of Public Health, NJ, USA
Assistant Professor (adjunct), Georgetown University School of Medicine,
Washington, DC, USA
www.drugsafetyconsultant.com
=====================

To be or not to be exclusive: the sutezolid story
Jane Andrews

Lancet Global Health Volume 4, No. 2, e89–e90, February 2016

DOI: http://dx.doi.org/10.1016/S2214-109X(15)00285-5

I arrived at the Johns Hopkins University campus with a sense of déjà vu;
it was my first visit to my alma mater in years. I had travelled to
Baltimore for a meeting about the licensing of sutezolid, a much-awaited
drug candidate for treatment of Mycobacterium tuberculosis. The research
faculty, technology transfer officers, university administration, and
advocates at the meeting felt the weight of the responsibility. We knew
that licensing a tuberculosis drug candidate could be a historic event.

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.

I declare no competing interests.

References
WHO. Global Tuberculosis Report.
http://www.who.int/tb/publications/global_report/gtbr15_main_text.pdf?ua=1;
2015. ((accessed Dec 21, 2015).)
View in Article
Dalton, T, Cegielski, P, Akksilp, S et al. Prevalence of and risk factors
for resistance to second-line drugs in people with multidrug-resistant
tuberculosis in eight countries: a prospective cohort study. Lancet. 2012;
380: 1406–1417
View in Article | Summary | Full Text | Full Text PDF | PubMed | Scopus (89)
Barbachyn, MR, Hutchinson, DK, Brickner, SJ et al. Identification of a
novel oxazolidinone (U-100480) with potent antimycobacterial activity. J
Med Chem. 1996; 39: 680–685
View in Article | CrossRef | PubMed | Scopus (191)
Brigdon, G, Hewison, C, and Varaine, F. New developments in the treatment
of drug-resistant tuberculosis: clinical utility of bedaquiline and
delamanid. Infect Drug Resist. 2015; 38: 367–378
View in Article | CrossRef
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).)
View in Article
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).)
View in Article
Medicines Patent Pool. About the medicines patent pool.
http://www.medicinespatentpool.org/about/. ((accessed Sept 24, 2015).)



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