Multidrug-resistant TB (MDR TB) is spreading in many regions, especially Asia and Eastern Europe. Currently there are an estimated 630,000 MDR TB cases worldwide, but only 1 in 5 has been accurately diagnosed.
2. From the FDA rationale for approving bedaquiline for MDR-TB -
Nonetheless, treatment for resistant TB is complex, costly, toxic and prolonged, requiring at least 5 second-line drugs for up to 2 years. Second-line drugs include injectable drugs (amikacin, kanamycin, capreomycin) and oral fluoroquinolones (FQs) and other second line drugs; the optimal use of which has not been well studied in randomized controlled trials, and whose safety when used in concert with various doses and regimens is not sufficiently described.
3. From the CDC guidance for the off-label use of bedaquiline -
A recently published individual patient data meta-analysis of 9,153 patients with MDR TB yielded a mortality rate of 15%.
4. From Insmed -
In the case of NTM the barrier to effective treatment is in gaining access to the interior of infected macrophages.
5. From Insmed's CEO -
IV amikacin is used to treat this patient population right now. You cannot get enough amikacin into the lung through IV to successfully address this disease.
6. From a curious observer -
If injecting amikacin into the bloodstream to kill NTM in the pulmonary macrophages is far less effective and far more hazardous than delivering concentrated amikacin directly to the NTM - must not the same be true of injecting amikacin into the bloodstream to kill TB in the pulmonary macrophages?
Won't the WHO, CDC, FDA, EMA and physicians worldwide all welcome a way of using amikacin which avoids compounding bloodstream toxicity caused by other TB / HIV therapies?
One of the less obvious significant benefits of the use of Arikace in MDR-TB was highlighted in the EMA COMP minutes posted by bwd -
[ In addition, the possibility of using amikacin by inhalation has the potential to result in a major contribution to patient care by allowing the outpatient administration of the product. ]
If that factor is viewed as potentially "a major contribution to patient care" in countries with a high standard of health care, imagine how much greater the impact would be in an African country with an epidemic of MDR-TB.
When a child is infected he/she can be moved to a medical facility where one physician can treat a hundred patients. When an adult with a dependent family is infected, someone trained to administer intravenous injections must visit him/her daily for at least six months.
There must be a considerable number of health care personnel who currently spend virtually all of their time travelling - day after day covering the same round of patients scattered over a large area.
[ In the case of NTM the barrier to effective treatment is in gaining access to the interior of infected macrophages ... IV amikacin is used to treat this patient population right now. You can't get enough amikacin into the lung through IV to successfully address this disease. ]
How can such a high rate of conversion to culture-negative - in patients, some of whom had remained culture-positive throughout two years of the curently-available treatment - not be viewed by the FDA as "reasonably predictive" of a clinical benefit over intravenous amikacin in the treatment of MDR-TB?