Towards ending tuberculosis: what gets measured gets done
New drugs push WHO into a novel role
For the first time in more than 40 years, a novel class of TB drugs with a novel mechanism of action, bedaquiline, was granted accelerated approval by the US Food and Drug Administration in December 2012. That approval, which was based on late phase II clinical data, created a unique dilemma for WHO. As the new drug was so desperately needed for the treatment of MDR-TB, the risk was great that countries would start using it in ways that would contribute to the rapid development of resistance – causing the world to lose its first new TB chemotherapeutic drug in more than four decades. The lack of phase III trial data on safety and efficacy created another worry: would early use of the drug actually do more harm to patients than good?
These concerns pushed WHO into the novel role of translating available data into guidelines and advice aimed at protecting both patient welfare and the lifetime of the drug. The following year, WHO issued its interim guidance for the inclusion of bedaquiline in the combination therapy of MDR-TB in accordance with existing WHO guidelines for the programmatic management of drug-resistant TB. The guidance set out requirements for patient selection, informed consent, drug administration, monitoring of efficacy, and pharmacovigilance to detect and manage adverse drug reactions and potential interactions with other drugs.
"Would early use of the drug actually do more harm to patients than good?"
Dr Chan, WHO Director-General
In 2014, WHO performed a similar evaluation of a second novel class of drugs with a novel mechanism of action, delamanid, still in phase III trials but granted conditional approval by the European Medicines Agency in April 2014. WHO interim guidance, published the same year, stipulated the specific conditions and safeguards that must be in place before programmes use delamanid to treat adults with MDR-TB.
In 2015, five anti-TB drugs, including bedaquiline and delamanid, were added to the WHO Model List of Essential Medicines. Four of the newly listed drugs were recommended by WHO for use in the treatment of MDR-TB and XDR-TB. The fifth drug, rifapentine, was indicated for the preventive treatment of latent TB in people living with HIV. The inclusion of these TB drugs in the Model List is expected to stimulate the interest of drug manufacturers to invest more in the development of new anti-TB medicines.
Also in 2016, WHO announced good news for the control of MDR-TB. A new DNA-based test was available that could identify genetic mutations in MDR-TB in just 24 to 48 hours, down from the three months previously required. In addition, WHO announced a new and shorter treatment regimen that allowed MDR patients to complete treatment in half the time and at nearly half the cost. Such innovative steps forward supported the feasibility of new goals.