The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the U.S. Food and Drug Administration (FDA) has granted approval for SIRTURO(bedaquiline) tablets as part of combination therapy in pediatric patients - those over the age of 12 and younger than 18 and weighing at least 66 pounds (30 kilograms) - with pulmonary multidrug-resistant tuberculosis (MDR-TB), when an effective treatment regimen cannot otherwise be provided.
Approved under the FDA's accelerated approval pathway based on time to sputum culture conversion, bedaquiline can now be used as part of combination therapy for eligible MDR-TB patients aged 12 years and over in the U.S. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA approval marks the first regulatory milestone as part of the company's global pediatric research and development (R&D) program for bedaquiline, with additional global regulatory filings planned. Further research is ongoing in children younger than 12 years of age using a pediatric formulation of bedaquiline.
TB is the world's deadliest infectious disease, claiming 1.6 million lives every year - more than HIV and malaria combined.i While TB often affects adults in their most productive years, all age groups are at risk. In 2017, an estimated 1 million children became ill with TB and 230,000 children died of the disease[i], underscoring the urgent need for effective pediatric TB treatments. Approximately 95% of childhood deaths from TB occur in Asia and sub-Saharan Africa.[ii]
'We are proud of what today's approval means for adolescent patients in the U.S., and we are hopeful about the future of our pediatric R&D program,' said Paul Stoffels, M.D., Vice Chair of the Executive Committee and Chief Scientific Officer, Johnson & Johnson. 'Despite being a major global health issue, TB lacks the attention and resources it requires - and the issue of TB in children is even more neglected. At Johnson & Johnson, we are committed to developing solutions that address the needs of all TB patients, including the youngest and most vulnerable.'
Today's U.S. FDA approval is supported by evidence from a single-arm, open-label, Phase 2 study that enrolled 15 pediatric patients with confirmed or probable MDR-TB infection. The patients were treated with the recommended dosage of bedaquiline for 24 weeks in combination with a background regimen. Bedaquiline was administered on the same schedule as it is for adults: 400 mg once daily for the first two weeks and 200 mg three times per week for the following 22 weeks. In the subset of patients with culture positive pulmonary MDR-TB at baseline, treatment with bedaquiline resulted in conversion to a negative culture in 6/8 (75%) patients at Week 24.
The most common adverse drug reactions were arthralgia in 6/15 (40%) patients, nausea in 2/15 (13%) patients and abdominal pain in 2/15 (13%) patients. Among the 15 patients, no deaths occurred during treatment with bedaquiline. Observed laboratory abnormalities were comparable to those in adults.
'In the past, MDR-TB was a diagnosis that left patients with few options. But fortunately, new treatments and other tools have brought a renewed sense of hope for patients,' said Jaak Peeters, Global Head, Johnson & Johnson Global Public Health, Janssen-Cilag GmBH. 'At Johnson & Johnson, we won't rest until we have optimized and helped to deliver effective MDR-TB treatment to patients of every age, wherever they may be.'
About the Bedaquiline Global Pediatric Development Program
As part of the company's commitment to the continued clinical development of bedaquiline, Janssen is conducting a Phase 2 sequential pediatric pharmacokinetic and safety study, C211, with four cohorts of patients in different age groups. The U.S. FDA approval of the use of bedaquiline in adolescents (12 to 30 kg) is supported by the results from Cohort 1 of the study. Cohort 2 of the study (5 to