HONG KONG – Phase II data of South Korea-based Qurient Co. Ltd.’s novel antibiotic candidate may offer hope that the first universal regimen to treat tuberculosis (TB) regardless of drug resistance status has been found.

Raising the dosage levels of telacebec, Qurient’s potentially first-in-class, orally available antibiotic, has been associated with greater reductions in viable TB bacterial load in sputum. The positive results from the prospective, randomized, open-label trial involving 61 patients with newly diagnosed, rifampicin- and isoniazid-susceptible pulmonary TB were published in The New England Journal of Medicine.

Kiyean Nam, CEO and chief strategy officer at Qurient, expressed his excitement at being able to achieve clinical proof of concept for telacebec as a new class of anti-TB agents. “This publication is recognized by global academics for the excellent clinical results of telacebec and provides hope to realize the first ‘100% effective regimen’ in making the distinction between drug-susceptible and drug-resistant TB obsolete,” Nam said.

In the study, patients were assigned to receive 14 days of oral telacebec at a dose of 100 mg, 200 mg or 300 mg once daily, or combination therapy with rifampicin, isoniazid, pyrazinamide and ethambutol. Serial sputum samples were then collected daily and the time to positivity in liquid culture was measured in hours.

The primary endpoint data showed a daily increase in the time samples required to become culture-positive after sputum inoculation and demonstrated that daily treatment with telacebec was able to reduce the number of live M. tuberculosis in a dose-dependent manner, with greater activity for increased doses over the 100-mg, 200-mg and 300-mg daily range.

“In a previously reported phase IIa study, results showed the possibilities of telacebec as part of a new regimen to shorten the time to treatment of multidrug-resistant tuberculosis from early bacterial activity study,” Kiwon Choi, the chief financial and operating officer of Qurient, told BioWorld.

“So this phase II data published in NEJM shows telacebec has potential as a new drug for MDR-TB.”

Using those data, Qurient now plans to submit an NDA to the U.S. FDA for telacebec.

“Because telacebec has orphan drug status, it could receive accelerated approval from U.S. FDA with phase II data,” said Choi.

Despite the designation, Qurient still plans to initiate a similar study as the phase IIb after conditional approval and subsequent drug launch.

The phase II trial took place in Cape Town, South Africa, under U.S. IND conditions and was headed by key South African opinion leaders in TB.

Telacebec was associated with acceptable adverse event rates, and adverse events were equally distributed among all groups. However, Qurient reported no serious adverse drug reactions and no adverse drug reactions that resulted in early withdrawal from the study.

“We have established clinical data for telacebec as a novel antibiotic, and we believe it provides a significant opportunity as a combination with other leading drugs to improve the treatment paradigm for all TB patients,” said Choi, but did not indicate whether the firm had partnerships currently being proposed.

Public health threat

TB remains one of the top 10 causes of death worldwide, according to Qurient.

In 2018, around 10 million people caught TB and the disease caused approximately 1.5 million fatalities. The World Health Organization has also stated that 484,000 people with TB showed resistance to rifampicin in that year. Thus, the need for new treatments has been growing.

“The bacterium that causes tuberculosis develops resistance to the antibiotics used to treat it. Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options,” said Amy Abernethy, principal deputy commissioner for the FDA.

“New treatments are important to meet patient national and global health needs. That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections.”

In August 2019, the FDA approved pretomanid tablets in combination with bedaquiline and linezolid for the treatment of a specific type of highly treatment-resistant TB. It marked the second time a drug has been approved under the limited population pathway for antibacterial and antifungal drugs, which is aimed at spurring the development of drugs targeting infections that lack effective therapies.

Besides telacebec, Qurient has a number of other programs in its pipeline.

“Qurient has three oncology programs: Q-702 (Axl/Mer.CSF1R inhibitor) and CDK7 inhibitor and iproteasome inhibitor. All three are licensed from Max Planck in Germany,” said Choi. “There are also two immune programs: Q-301 for atopic dermatitis and Q-601 for flu adjuvant.”

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