New from WHO

Embargoed until 10:30 CET 28 October 2014

Interim guidance on use of Delamanid

in the Treatment of MultidrugResistant Tuberculosis (MDR-TB)

WHO END TB STRATEGY - components

1. INTEGRATED, PATIENT-CENTRED CARE AND PREVENTION
A. Early diagnosis of tuberculosis including universal drug-susceptibility testing, and systematic
screening of contacts and high-risk groups
B. Treatment of all people with tuberculosis including drug-resistant tuberculosis, and patient
support
C. Collaborative tuberculosis/HIV activities, and management of co-morbidities
D. Preventive treatment of persons at high risk, and vaccination against tuberculosis

2. BOLD POLICIES AND SUPPORTIVE SYSTEMS

A. Political commitment with adequate resources for tuberculosis care and prevention
B. Engagement of communities, civil society organizations, and public and private care providers
C. Universal health coverage policy, and regulatory frameworks for case notification, vital
registration, quality and rational use of medicines, and infection control
D. Social protection, poverty alleviation and actions on other determinants of tuberculosis

3. INTENSIFIED RESEARCH AND INNOVATION

A. Discovery, development and rapid uptake of new tools, interventions and strategies
B. Research to optimize implementation and impact, and promote innovations

NEED FOR NEW DRUGS IN TB CARE

Drug resistance is a major threat to global TB care and control.
WHO estimates nearly 500,000 new multidrug-resistant
tuberculosis (MDR-TB) cases occur each year. These patients
are resistant to two most powerful TB drugs (RIF & INH)
Current treatment regimens for drug-resistant TB are complex,
lengthy, toxic and expensive.

Only about one half of MDR-TB patients started on treatment

globally are reported to be treated successfully,
About a third of MDR-TB cases may have strains with
additional resistance to fluoroquinolones and/or injectable
drugs (aminoglycosides or capreomycin), leaving only other
even more toxic drugs available

Delamanid
Novel drugs are presently or soon entering Phase III
trials for the treatment of MDR-TB.
Delamanid, a novel TB drug, developed by Otsuka,
was granted conditional approval by the European
Medicine Agency in April 2014. I
Information about this new drug however remains
limited, since it has only been through Phase IIb
trial and studies for safety and efficacy.

Phase III trial is underway

Assessment of delamanid
Considering
the global MDR-TB crisis,
the limited therapeutic options available for this life-

threatening condition,
the need to promote safe and responsible use of TB drugs,
WHO convened an Expert Group in April 2014 to review the
available evidence on the efficacy, safety and effectiveness of
delamanid, a new drug for the treatment of MDR-TB
Aim of the Expert Group to advise WHO on development of
interim recommendations on its use in conjunction with WHOrecommended MDR-TB treatment.
Based on this advice, WHO developed full interim guidance
approved by its Guidelines Review Committee. A similar process
whas followed in 2013 for bedaquiline

WHO recommends five conditions for use

1. Proper patient inclusion: Special caution is required when delamanid is used in people
aged 65 and over, in adults living with HIV, patients with diabetes, hepatic or severe
renal impairment, or those who use alcohol or substances. Use in pregnant and
breastfeeding women and children is not advised.
2. Adherence to WHO recommendations when designing MDR-TB treatment regimens:
The inclusion of four effective second-line drugs and pyrazinamide, as well as other
principles of designing a MDR-TB regimen, must be followed when delamanid is included
as part of treatment. Delamanid should not be introduced alone into a regimen in which
the companion drugs are failing to show effectiveness.
3. Effective treatment and monitoring: Treatment must be closely monitored for
effectiveness and safety, using sound treatment and management protocols approved by
the relevant national authorities.
4. Pharmacovigilance and management of adverse events: active pharmacovigilance
measures must be in place to ensure early detection and proper management of
adverse drug reactions and potential interactions with other drugs.
5. Informed consent: Patients must be fully aware of the potential benefits and harms of
the new drug, and give informed consent before embarking on treatment

Also NEW:
WHO POLICY IMLEMENTATION PACKAGE for the
introduction of new TB drugs
GOAL: To support countries in preparing for introduction of new TB drugs and/or
regimens, based on WHO policy guidance, in order to better serve patients and
communities in need. There are six elements:

1. Minimum requirements for country preparedness and planning.

2. National Implementation plan for introduction of new TB drugs
and/or regimens.
3. Monitoring and evaluation of new drugs and regimens, including
pharmacovigilance and drug resistance surveillance.
4. Private sector engagement.
5. Systems approach for ensuring uninterrupted supply of qualityassured drugs.
6. Operational research.