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Sutezolid With 3-Drug Combo Appears Safe and Effective in Multidrug-Resistant TB

— Sutezolid may be a replacement for linezolid in these patients, researcher says

Last Updated February 22, 2023
MedpageToday

SEATTLE -- Adding the oxazolidinone antibiotic sutezolid to a three-drug combination appeared to be safe and effective for people with multidrug-resistant tuberculosis (TB), according to a dose-finding phase II study.

Across five treatment arms that included four different doses of sutezolid with bedaquiline, delamanid, and moxifloxacin at standard doses, there was a similar increase in the Mycobacterium Growth Indicator Tube Time-to-Positivity (MGIT TTP) at 12 weeks, reported Norbert Heinrich, MD, a senior scientist at Ludwig Maximilian University Hospital in Munich, during the Conference on Retroviruses and Opportunistic Infections.

"The drug is a safe combination partner within the four-drug combination tested," he said, noting, however, that he and his team "were not able to demonstrate a dose effect on slope of TTP over time for sutezolid when added to a potent three-drug combination, which may have been a limitation to our study design."

The addition of sutezolid to the three-drug combination appeared to show a steeped MGIT TTP slope, he said.

Heinrich suggested that the use of bedaquiline, delamanid, and moxifloxacin as the therapy backbone with sutezolid appeared to show similar efficacy as one would expect with the recommended first-line regimen of isoniazid, rifampin, pyrazinamide, and ethambutol.

As for safety, a total of nine of 75 patients experienced serious adverse events.

"We observed a good safety profile with the combination of drugs with and without sutezolid," Heinrich said. There were four cases of QT cardiac prolongation >60 ms -- a regulator-demanded cutoff, although none of the QT prolongations lasted longer than the clinically important 500 ms.

There was also one case of grade 4 liver toxicity and one case of neutropenia in a patient who was also taking antiretroviral therapy for HIV. "No clinical neuropathy occurred during 12 weeks of treatment with sutezolid," he added. "No anemia or thrombocytopenia developed among patients on sutezolid in the 12 weeks of the study."

Heinrich said that while linezolid is considered a critical component of current multidrug-resistant TB therapy, the agent is too toxic for wider use. "The problem with linezolid is that its use is associated with neuropathy and myelosuppression," he told 鶹ý. "We think that sutezolid could be a replacement for linezolid in patients with resistant tuberculosis."

Of the patients treated with sutezolid, 14% experienced mild or moderate increases in alanine transaminase.

"We have not had a new drug for the treatment of these patients in decades," said Landon Myer, MD, PhD, of the University of Cape Town in South Africa. "The field in general sucks. We have very few new medications to help people with multidrug-resistant tuberculosis."

"Linezolid has difficult side effects that prevent its wider use. This early data about sutezolid seems to show it to be better as far as adverse events are concerned. The results are encouraging but we need more data, and we need better drugs too," he told 鶹ý.

In the PanACEA Sutezolid Dose-Finding and Combination Evaluation (SUDOCU) study, participants with drug-sensitive pulmonary TB were randomized to sutezolid 0 mg, 600 mg once daily, 1,200 mg once daily, 600 mg twice daily, or 800 mg twice daily, in addition to bedaquiline, delamanid, and moxifloxacin at standard doses, for 12 weeks.

Participants were recruited from four sites in Tanzania and South Africa, 75% of whom were men. Median age ranged from 30 to 36 across the study arms, and two were living with HIV.

The primary efficacy endpoint was the slope of decline of bacterial load, measured weekly for 12 weeks. Safety outcomes included the oxazolidinone class toxicities myelosuppression and neuropathy.

Heinrich said he is looking forward to further studies with sutezolid, although his work with the drug is now being passed on to other groups that will likely perform larger international studies.

  • author['full_name']

    Ed Susman is a freelance medical writer based in Fort Pierce, Florida, USA.

Disclosures

The study was financed by Sequella and the Global TB Alliance.

Heinrich disclosed relationships with LegoChem Biosciences.

Myer disclosed no conflicts of interest.

Primary Source

Conference on Retroviruses and Opportunistic Infections

Heinrich N, et al "PanACEA SUDOCU combination dose-finding trial shows sutezolid is a safe oxazolidinone" CROI 2023.