Tuberculosis

Delamanid for Tuberculosis Approved in Europe, New Drugs Under Study

The European Union recently approved the new anti-tuberculosis drug delamanid (Deltyba) for use in combination therapy for people with multidrug-resistant TB. In related news, the Stop TB Partnership announced that it will make another new drug, bedaquiline (Sirturo), available in more than 100 low- and middle-income countries.

Multidrug-resistant tuberculosis (MDR-TB), which does not respond to standard antibiotics and requires more intensive combination regimens, is a growing threat worldwide. Before the approval of new drugs, only about half of MDR-TB patients who received therapy were successfully treated. Extensively drug-resistant TB (XDR-TB) is resistant even to backup drugs and new agents are urgently needed.

 Delamanid 

In late April, Japan's Otsuka Pharmaceutical Co. announced that the European Commission granted the first marketing authorization for delamanid (formerly known as OPC-67683) to treat MDR-TB. The European Medicines Agency initially rejected the drug in July 2013, but the company successfully appealed with longer-term safety and efficacy data.

Delamanid is indicated for use as part of combination therapy for adults with pulmonary MDR-TB who cannot put together an effective regimen due to drug resistance or lack of tolerability.

As described in the June 7, 2012, New England Journal of Medicine, delaminid combination therapy demonstrated good activity against highly resistant TB, clearing infection in 45% of participants in a multinational clinical trial. The drug has a novel mechanism of action -- interfering with metabolism of Mycobacterium tuberculosis cell walls -- so it retains activity against TB strains resistant to first-line agents such as isoniazid and rifampicin.

To guard against development of resistance to the new drug, Otsuka devised a Responsible Access Program that includes strict distribution control, professional medical education about the proper use of delamanid, and a patient registry to track safety and efficacy.

"The TB community has waited a long time for a new medication for MDR-TB," stated Wiel de Lange from University Medical Center in Groningen in an Otsuka press release. "With increasing rates of resistance to existing medications and globally less than half of all MDR-TB cases successfully treated, Deltyba is clearly a welcome new option."

Bedaquiline

Also in late April, the Stop TB Partnership announced that it has begun distributing Janssen's MDR-TB drug bedaquiline (formerly TMC207) through its Global Drug Facility and its procurement agent, the International Dispensary Association. In 2013 GDF provided quality-assured TB drugs to more than 130 countries, including 24 considered to have a high burden of MDR-TB.

Bedaquiline was approved by the U.S. Food and Drug Administration and European Commission in late 2012 -- the first new TB drug approval in more than 40 years. Like delamanid, it works by a novel mechanism and remains effective against Mycobacterium tuberculosis that has become resistant to older drugs. It is also indicated for use in combination therapy and has controlled distribution to ensure that inappropriate use does not compromise its effectiveness.

A Stop TB Partnership FAQ about bedaquiline procurement is available online.

PamZ

Finally, the TB Alliance recently announced that the Bill and Melinda Gates Foundation will help fund the global STAND (Shortening Treatments by Advancing Novel Drugs) trial, a Phase 3 study of another promising regimen for MDR-TB known as PamZ, combining Novartis' PA-824 plus the older drugs pyrazinamide and moxifloxacin.

The PamZ combination shortens MDR-TB treatment from 18-24 months to 6 months and eliminates the need for injected drugs, which would improve adherence and reduce cost. The STAND trial is expected to include 50 study sites across Africa, Asia, Eastern Europe, and Latin America.

"The results from early-phase research suggest that this new drug regimen could provide the breakthrough we need to accelerate progress against this deadly and dangerous disease," Bill Gates stated in a TB Alliance press release. "PaMZ could dramatically reduce the time required to cure drug-resistant TB from 2 years to just 6 months, and it could cut the cost of curing drug-resistant TB in low-income countries from thousands of dollars to just a fraction of that cost." Gates urged other funders to step forward and contribute funds for the trial.

See also: CROI 2014: New Drugs, Novel Combos Top Tuberculosis News at Conference

5/28/14

Sources

Otsuka Pharmaceutical Co. Otsuka Wins European Marketing Authorization for Deltyba (delamanid). Press release. April 30, 2014.

Stop TB Partnership/Global Drug Facility. Stop TB Partnership’s Global Drug Facility to Distribute Bedaquiline (Sirturo) Developed by Janssen. Press release. April 30, 2014.

TB Alliance. New Tuberculosis Drug Regimen Will Move to Landmark Phase 3 Clinical Trial. Press release. April 23, 2013.