The Invitation to Manufacturers of Antituberculosis Medicines to submit an Expression of Interest for Product Evaluation to the WHO Prequalification Unit has been updated to include key formulations of rifapentine for use in children and adults, following a request by the WHO Global Tuberculosis Programme. Rifapentine is a vital component of shorter regimens for the treatment of TB infection, which are easier to complete than the longer regimens. It is also a key component of the 4-month regimen for the treatment of drug-susceptible pulmonary TB that was recently assessed by a WHO convened Guideline Development Group. The Group found the 4-month regimen to be a possible alternative to the current standard 6-month regimen, allowing faster cure and easing the burden on both patients and the healthcare system.
"WHO is encouraging manufacturers to develop quality-assured formulations of rifapentine and submit them for product evaluation to the WHO Prequalification Unit to increase their access and affordability" said Dr Tereza Kasaeva, Director of WHO's Global TB Programme. "Streamlining the formulations of rifapentine and other essential medicines to be prioritized for development is vital to focus market efforts to develop products of the greatest need for TB patients and persons exposed to TB, including young children."
The WHO Global TB Programme has also submitted applications for the inclusion of the rifapentine 300 mg scored tablet and a fixed-dose combination (FDC) of rifapentine and isoniazid (300 mg/300 mg) in the WHO Model List of Essential Medicines (EML). Inclusion of these formulations in the WHO EML will facilitate country efforts to use rifapentine-containing regimens. The decision of the EML Expert Committee will be published in the coming months.
The current price of adult rifapentine formulations has curtailed the drug's accessibility. This has contributed to the slower than anticipated introduction of shorter TB preventive treatment regimens globally and could also potentially hinder the uptake of the shorter drug-susceptible TB treatment regimen in the future. Further reductions in the price of rifapentine will require additional suppliers to enter the market.
The modifications to the Invitation to Manufacturers are in line with WHO guidelines and include key formulations that will help reduce pill burden in regimens, improving the likelihood of treatment completion:
- The child-friendly formulation of rifapentine – a 150 mg scored dispersible tablet formulation: This is the formulation that participants of the PAediatric Drug Optimization for TB medicines (PADO-TB) review meeting, a forum for clinicians, researchers, and other key stakeholders convened by WHO in September 2020, agreed to prioritize for development. This formulation of rifapentine can allow dosing across age groups and can serve multiple indications, including for TB preventive treatment and for the treatment of drug-susceptible TB, should shorter rifapentine containing regimens be recommended by WHO in the future for all age groups.
- For adults, a rifapentine 300 mg scored tablet formulation: This stands out as the most versatile formulation for meeting dosing requirements of current regimens for TPT and the treatment of drug-susceptible TB with the rifapentine-containing 4-month regimen.
- A FDC of rifapentine and isoniazid (300 mg/300 mg) that facilitates easier administration of the 3-month TPT regimen of isoniazid and rifapentine (3HP) in persons aged 13 years and above.
WHO's Global TB Programme will continue reviewing new evidence, when it becomes available, to inform updated guidelines, and will work with partners to improve access to key TB medicines for prevention and treatment for all patients, in line with WHO recommendations.
