The recent regulatory nod for Viatris’ Dovprela (ingredient: pretomanid) for the treatment of extensively drug-resistant tuberculosis (XDR-TB) will shorten the disease treatment period, an expert said.
Viatris Korea held a news conference on Tuesday to mark World TB Day (March 24) to share the nation’s multidrug-resistant TB (MDR-TB) management status, diagnosis, treatment, and clinical value of pretomanid.
Professor Shim Tae-sun of pulmonology and critical care at Asan Medical Center spoke on the unmet needs of MDR-TB and XDR-TB treatment and introduced the latest treatment strategy using new drugs.
MDR-TB refers to resistance to isoniazid and rifampin, the two most essential drugs among the first-line anti-TB medicines.
XDR-TB refers to simultaneous resistance to one or more quinolone drugs (ofloxacin, levofloxacin, and moxifloxacin), which are most effective among second-line anti-TB agents, and to one or more of amikacin, capreomycin, and kanamycin.
“Although 90 percent of TB patients are cured with a long-term treatment for at least six months, irregular drug use can cause relapse or treatment failure and lead to MDR-TB or XDR-TB that are more difficult to treat,” Shim noted.
Progress to MDR-TB cuts the treatment success rate to 50 percent, causes higher adverse event rates because of second-line drugs, and prolongs the treatment period to 18 to 24 months, he warned.
“XDR-TB treatment is much more challenging with a higher possibility of death,” he said. “To improve the treatment environment and raise the treatment success rate, we should have a diagnosis system to check drug susceptibility more quickly and a new treatment strategy that shortens the treatment period.”
The 2020 TB care guidelines recommend rapid susceptibility tests of isoniazid and rifampin on the first culture strain or acid-fast smear-positive samples from all TB patients to detect MDR-TB quickly. Also, when MDR-TB is confirmed, doctors are recommended to run susceptibility tests on quinolone drugs, according to the guidelines.
Although the PCR-based rapid test became available to diagnose MDR-TB and XDR-TB, there are still unmet needs in the short-term treatment using new drugs, Shim pointed out.
In Korea, physicians do not use combination therapy using seven drugs, including bedaquline, because of high drug resistance rates. The treatment period is still long, between nine and 12 months, which makes it difficult to control patients’ drug compliance, making treatment likely to fail, Shim said.
He expected that recently introduced BPaL therapy, consisting of bedaquiline, pretomanid (Dovprela), and linezolid, will shorten the treatment period for MDR-TB and XDR-TB patients and raise the treatment success rate.
Dovprela was developed in partnership between Viatris and TB Alliance, a non-profit organization. It became a new XDR-TB treatment approved in 50 years.
In Korea, the treatment was authorized in October last year in combination with bedaquiline and linezolid for BPaL therapy in adults to treat pulmonary XDR or treatment-intolerant or nonresponsive MDR TB.
The phase-3 Nix-TB trial, which supported the marketing approval, showed that BPaL therapy demonstrated a 92 percent treatment success rate in MDR-TB patients, and 89 percent in XDR TB patients, in six months. This suggested that BPaL could be used for short-term treatment.
BPaL therapy is the first “ready-to-use” combo consisting of pills only. The therapy reduced the risk of adverse reactions and improved medication compliance with fewer drugs, compared to the existing treatment guidelines using at least four agents during the intensive treatment period.
Still, Korea has many challenges to using BPaL therapy effectively, Shim said.
“BPaL therapy is not used in Korea because it is not covered by health insurance,” he said. “As linezolid is used in low-dose in Korea, a related society delivered an opinion that off-label drug use can be included in the reimbursement criteria for BPaL therapy.”