A new antibiotic called sorfequiline, a type of next generation diarylquinoline, has achieved good results for treating drug sensitive tuberculosis (TB) in combination with the antibiotics pretomanid and linezolid in a Phase II study.
The trial results, which were presented at the by TB Alliance at the Union World Conference on Lung Health in Denmark this week, showed that the sorfequiline (also known as TBAJ-876) combination treatment performed better than a standard drug-sensitive TB combination treatment of isoniazid, rifampin, pyrazinamide, and ethambutol.
Notably, the researchers also found sorfequiline had higher activity than a bedaquiline combination treatment. Bedaquiline is the first next-generation diarylquinoline antibiotic to be approved in 2012 for treatment of multidrug-resistant tuberculosis.
Due to the approval of bedaquiline, many people with drug-resistant TB can now be treated in six months, which is similar to the standard time for drug-sensitive TB treatment, using a combination treatment of the antibiotics bedaquiline, pretomanid, and linezolid (known as BPaL).
“The development of the BPaL regimen allowed us to reduce treatment time for most drug-resistant TB to six months, a critical development for patients,” said Mel Spigelman, MD, president and CEO of TB Alliance, in a press statement.
“Now, we have an opportunity to shorten treatment even further—representing an important milestone toward our goal of developing an ultra-short regimen capable of treating both drug-sensitive and drug-resistant TB.”
This study tested three different doses of sorfequiline (25, 50 and 100mg) in combination with pretomanid and linezolid, as well as the BPaL regimen and the standard four antibiotic combination for drug sensitive TB.
The primary endpoint for the study was time to stable sputum conversion (SSC) by week 8. This was achieved by 59% of the 100mg sorfequiline group versus 45% of the BPaL group and 45% of the standard treatment group. In the highest dosage group, 64% of the sorfequiline group was able to stop treatment at week 15 if they had a negative sputum result at week 8.
“For decades, the standard treatment time for tuberculosis has been six months,” said Maria Beumont, MD, vice president and chief medical officer at TB Alliance. “With BPaL, we proved that we can dramatically simplify and shorten drug-resistant TB treatment, but that was just the first step. With regimens currently in development, we believe we can shorten and simplify treatment even further—for all forms of TB. The results from this trial bring us closer to our goal and the eventual eradication of TB as a global health threat.”
An advantage of sorfequiline is that so far it has a better safety profile compared to bedaquiline, with lower cardiac toxicity signals and better patient tolerance to date. Similar to bedaquiline it is designed to be an oral drug making the long treatment needed for eradication of TB easier for patients.
The TB alliance is now planning to move onto Phase III trials of sorfequiline and is also testing a long-acting injectable treatment that could potentially reduce treatment time to as little as one month.
