Deltyba
Active
Substance: delamanid
Common Name: delamanid
ATC Code: J04AK06
Marketing Authorisation Holder: Otsuka Novel Products GmbH
Active Substance: delamanid
Status: Authorised
Authorisation Date: 2014-04-28
Therapeutic Area: Tuberculosis, Multidrug-Resistant
Pharmacotherapeutic Group: Antimycobacterials
Therapeutic
Indication
Deltyba is
indicated for use as part of an appropriate combination regimen for pulmonary
multi-drug resistant tuberculosis (MDR-TB) in adult patients when an effective
treatment regimen cannot otherwise be composed for reasons of resistance or
tolerability.
Consideration
should be given to official guidance on the appropriate use of antibacterial
agents.
What is Deltyba
and what is it used for?
Deltyba is a
tuberculosis medicine that contains the active substance delamanid.
Tuberculosis is an infection caused by the bacterium Mycobacterium tuberculosis
(M. tuberculosis). Deltyba is used in adults with tuberculosis that is
affecting the lung and that is multi-drug resistant (resistant to at least
isoniazid and rifampicin, two standard anti-tuberculosis medicines). It is used
together with other standard medicines and when other combinations without this
medicine cannot be used either because the disease is resistant to them or
because of their side effects.
Because the
number of patients with tuberculosis is low in the EU, the disease is
considered ‘rare’, and Deltyba was designated an ‘orphan medicine’ (a medicine
used in rare diseases) on 1 February 2008.
How is Deltyba
used?
Deltyba can only
be obtained with a prescription and treatment should be started and monitored
by a doctor who is experienced in the treatment of multi-drug resistant
tuberculosis.
The medicine is
available as tablets (50 mg) and the recommended dose is two tablets twice a
day taken together with food. Deltyba is given for 6 months together with other
standard medicines. Treatment with these standard medicines should continue as
recommended by official guidelines after completion of Deltyba treatment. For
further information, see the package leaflet.
How does Deltyba
work?
The active
substance in Deltyba, delamanid, is an antibiotic active against M.
tuberculosis. Although the precise mode of action is unclear, delamanid is
known to block the production of methoxy-mycolic and keto-mycolic acids, two
essential components of the cell walls of M. tuberculosis, which will cause the
bacteria to die.
What benefits of
Deltyba have been shown in studies?
The effects of
Deltyba have been looked at in one main study involving 481 adults with
tuberculosis resistant to standard treatments. Patients in the study were given
Deltyba or placebo (a dummy treatment) for 2 months in addition to their other
treatments. The main measure of effectiveness was the proportion of patients
who no longer had the bacteria in their sputum (phlegm). After 2 months of
treatment more than 40% of the patients who were taking Deltyba no longer had
the bacteria in their sputum compared with 30% of the patients who were taking
placebo.
After the main
study had finished, patients had the option to receive treatment with Deltyba
for 6 months in an extension study. In addition, a majority of patients who
entered the main study were followed up for up to 24 months afterwards. Looking
at the results of these follow-up studies together, 2 years after starting
treatment 75% of patients who received Deltyba for 6 months or more had no
bacteria in their sputum compared with 55% of patients who received Deltyba for
2 months or less.
What are the
risks associated with Deltyba?
The most common
side effects with Deltyba (which may affect around a third of patients) are
nausea, vomiting and dizziness. The most serious side effect is QT prolongation
(an alteration of the electrical activity of the heart which can cause a
life-threatening abnormality of heart rhythm). Other important side effects are
anxiety, paraesthesia (unusual sensations like pins and needles) and tremor
(shaking). For the full list of all side effects reported with Deltyba, see the
package leaflet.
Deltyba must not
be used in patients who have low levels of albumin (a blood protein). It must
also not be used in patients who are taking certain other medicines that affect
the way Deltyba is broken down in the body. For the full list of restrictions,
see the package leaflet.
Why is Deltyba
approved?
The Agency’s
Committee for Medicinal Products for Human Use (CHMP) decided that Deltyba’s
benefits are greater than its risks and recommended that it be approved for use
in the EU. The Committee considered that the benefits of Deltyba had been shown
for patients with multi-drug resistant tuberculosis affecting the lung.
Although the main study was of short duration and the follow-up studies had
shortcomings, the CHMP took the view that the effects shown after the initial 2
months of treatment are likely to be sustained for the full treatment duration.
The CHMP noted that an on-going clinical study will provide confirmation on the
long-term effectiveness. In addition, the CHMP required that an additional
study should be carried out to confirm that the current recommended dose is the
most appropriate dose.
Regarding the
safety of Deltyba, the safety profile was considered manageable and several
measures were introduced to minimise the risks, including a study to confirm
the long-term safety. Furthermore the Committee highlighted the medical need
for new agents to treat multi-drug resistant tuberculosis.
Deltyba has been
given ‘conditional approval’. This means that there is more evidence to come
about the medicine, which the company is required to provide. Every year, the
European Medicines Agency will review any new information that becomes
available and this summary will be updated as necessary.
What information
is still awaited for Deltyba?
Since Deltyba
has been granted a conditional approval, the company that markets Deltyba will
carry out further studies to confirm the long-term effectiveness and safety of
Deltyba. A further study will also be carried out to confirm the most
appropriate dose.
What measures
are being taken to ensure the safe and effective use of Deltyba?
A risk
management plan has been developed to ensure that Deltyba is used as safely as
possible. Based on this plan, safety information has been included in the
summary of product characteristics and the package leaflet for Deltyba,
including the appropriate precautions to be followed by healthcare
professionals and patients.
In addition, the
company that markets Deltyba will provide educational material for healthcare
professionals, explaining how to use the medicine safely in order to avoid
problems such as the development of resistance and side effects on the heart,
as well as the risks in pregnancy or women who are breast-feeding.
Other
information about Deltyba
The European
Commission granted a marketing authorisation valid throughout the European
Union for Deltyba on 28 April 2014.
For more
information about treatment with Deltyba, read the package leaflet (also part
of the EPAR) or contact your doctor or pharmacist.
Source: European
Medicines Agency
