FDA Grants Full Approval to Johnson & Johnson’s Sirturo for Pulmonary Tuberculosis Caused by Mycobacterium Tuberculosis Resistant to Rifampicin and Isoniazid

Image Credit: Adobe Stock Images/Mariya Sorvacheva

The FDA has granted a full approval to Johnson & Johnson’s (J&J) Sirturo for use in combination therapy in treating pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis resistant to rifampicin and isoniazid. According to the company, the approval by the FDA effectively removes previous label restrictions that were part of the medicine's accelerated approval in December 2012. The regulatory action was based on promising results from the Phase III STREAM Stage 2 study.¹

STREAM Stage 2 was the first large-scale, randomized, multi-country open-label clinical study to evaluate the efficacy and safety of an all-oral bedaquiline-containing regimen for treatment of MDR-TB. Between March 28, 2016, and January 28, 2020, 1436 participants were screened with 588 individuals randomly assigned to either the 2011 WHO regimen, which was terminated early, a nine-month control regimen, a nine-month oral regimen with bedaquiline (primary comparison), or a six-month regimen with bedaquiline and eight weeks of second-line injectable. The primary endpoint of the trial was a composite outcome, including both bacteriological unfavorable events and non-bacteriological unfavorable events.^1,2

Results found that 83% of participants on the oral regimen achieved a favorable outcome compared to 71% in the control regimen in the mITT analysis. Additionally, 88% of participants on the oral regimen reported a positive outcome in the per-protocol analysis, while 76% of those on the control regimen experienced the same.

At 76 weeks of treatment, 53% of participants in the control regimen and 50% in the oral regimen reported an adverse event (AE) grade 3 or 4, with five participants in the in the control regimen and seven in the oral regimen dying. Reported AEs included hepatic disorders, which resulted in a severe hepatic event in 10% of those on the control regimen and 12% on the oral regimen.

Despite its promising results, the authors of the study acknowledged that the open-label design might have influenced decisions on regimen change, mainly for non-bacteriological reasons.²

“In conclusion, STREAM stage 2 has shown that two short-course, bedaquiline-containing regimens are not only non-inferior but superior to a 9-month injectable-containing regimen,” reported the authors of the study.” The STREAM stage 2 fully oral regimen avoided the toxicity of aminoglycosides, and the 6-month regimen was highly effective, with reduced levels of ototoxicity. These two regimens offer promising treatment options for patients with MDR or rifampicin-resistant tuberculosis. However, safer and simpler alternatives are still needed.”

Last year, J&J announced that it would refrain from enforcing patents for Sirturo in treating MDR-TB in 134 low- and middle-income countries, aiming to provide generic manufacturers with the opportunity to manufacture and sell high quality generic versions of the treatment without worrying that the company would prevent it.³

“Underdiagnosis remains the most significant barrier to treatment, with nearly two-thirds of the 450,000 people who develop MDR-TB each year not diagnosed and enrolled on treatment,” said Howard Reid, global head, global public health & social impact, Johnson & Johnson, in a press release. “This addresses any misperception that access to our medicine is limited or restricted and builds on our decade of investments in collaborative efforts to help countries sustainably scale up access and bring people living with MDR-TB into treatment.”

References

1. Johnson & Johnson Receives Approval from U.S. FDA and European Commission for SIRTURO® (bedaquiline). Johnson & Johnson. July 2, 2024. Accessed July 8, 2024. https://www.jnj.com/media-center/press-releases/johnson-johnson-receives-approval-from-u-s-fda-and-european-commission-for-sirturo-bedaquiline

2. Evaluation of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): an open-label, multicentre, randomised, non-inferiority trial. The Lancet. November 8, 2022. Accessed July 8, 2024. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02078-5/fulltext#seccestitle160

3. Johnson & Johnson Confirms Intent Not to Enforce Patents for SIRTURO® (bedaquiline) for the Treatment of Multidrug-Resistant Tuberculosis in 134 Low- and Middle-Income Countries. Johnson & Johnson. September 29, 2023. Accessed July 8, 2024. https://www.jnj.com/media-center/press-releases/johnson-johnson-confirms-intent-not-to-enforce-patents-for-sirturo-bedaquiline-for-the-treatment-of-multidrug-resistant-tuberculosis-in-134-low-and-middle-income-countries