Where
are the innovations in tuberculosis drug discovery?
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WHO
has released
a report that highlights a serious lack of antibiotics in clinical
development; a worrying finding in an era of antimicrobial resistance.
The report identifies a particular shortage of antibiotics under
development for multidrug-resistant tuberculosis, which is a disease
that kills a quarter of a million people every year.
The WHO analysis aimed to identify products that were in clinical
development up to May, 2017, for the treatment of tuberculosis,
Clostridium difficile, and diseases caused by pathogens on the WHO
priority pathogen list. WHO also assessed whether these products were
innovative. Their definition of innovative was based on whether they
were a new chemical class, had a new target or binding site, had a new
mode of action, or had no cross resistance to other antibiotic classes.
For tuberculosis, they found that only seven products are currently in
clinical development. Five of these products are categorised as
innovative, but only one—pretomanid—is in phase 3
clinical development. These figures are an improvement on 2000, when no
tuberculosis drugs were in clinical development and the TB Alliance was
formed to address the issue. However, the figures are still well short
of the targets set out by the Stop TB Partnership Global Plan
2011–2105. Additionally, only two new antibiotics for
tuberculosis have reached the market in over 70
years—delamanid and bedaquiline—but limited access
to these newly licensed drugs has been highlighted, with fewer than 5%
of people in need being treated with them according to Medecins Sans
Frontieres. Reasons for the restricted access include their high price,
and the drugs not being registered in many high-burden countries.
The limited drug pipeline for tuberculosis can be attributed to a
substantial lack of funding. According to the US-based Treatment Action
Group, global funding for all tuberculosis research and development
almost doubled between 2005 and 2011; however, funding has plateaued
since 2009. In 2015, total global funding was US$620 million, which is
far from the 2011–2015 Global Plan's target of
$2·2 billion. Treatment Action Group notes that the reduced
funding in 2015 was due to the payment cycles of major funders, and
declining investment from the largest pharmaceutical funder, Otsuka,
whose new drug delamanid is in the final stages of phase 3 clinical
trials.
In this context, it is welcome news that the Global Antibiotic Research
and Development Partnership (GARDP) announced more than €56
million has been raised to fund an initiative to fight antibiotic
resistance. The partnership was launched in May, 2016, by WHO and the
Drugs for Neglected Diseases initiative, with the aim of developing and
delivering new treatments for bacterial infections for which drug
resistance is present or emerging, or for which current treatments are
inadequate. GARDP will target products that the pharmaceutical industry
will likely not develop due to lack of profitability or other reasons,
and will pilot the use of alternative incentive models, removing the
link between the cost of research and development and the sales of
antibiotics. GARDP has four main focus areas: sexually transmitted
infections, a programme to revive abandoned antibiotic development
projects, neonatal sepsis, and paediatric antibiotics. However, it has
no specific programme to tackle multidrug-resistant tuberculosis.
Despite poor funding for tuberculosis research and development, the
latest analyses of the Global Burden of Disease study show that deaths
caused by tuberculosis in 2016 were down by nearly 21% since 2006, and
the incidence of tuberculosis was down by 1·7%. However,
this rate of decline is not sufficient to meet the UN Sustainable
Development Goal to end the epidemic of tuberculosis by 2030, with not
a single country projected to achieve this goal. The identification of
new drugs is not the only strategy for tackling tuberculosis; efforts
are also being made to improve diagnosis, infection prevention and
control, and to ensure appropriate use of existing and future
antibiotics in the human, animal, and agricultural sectors. But without
innovations in the market to help develop new treatments for
multidrug-resistant tuberculosis, the UN Sustainable Development Goal
will remain out of reach.
Articel By : Prof.
dr. Tjandra Yoga Aditama, SpP(K), MARS, DTM&H, DTCE
Source
: http://www.thelancet.com/journals/lanres
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