Delamanid for MDR-TB: Current Development Progress and Ongoing Access Plans
Charles Wells (Otsuka)
Otsuka believes the way forward for successful introduction of delamanid requires: long-term strategic planning; careful introduction in quality TB management programs accompanied by robust risk management plans; country level support for implementation; prevention of additional drug resistance; and strengthened pharmacovigilance systems. Sometimes these core principles may be perceived as conflicting with the urgency to make delamanid available as soon as possible, to as many people as possible, worldwide. Following this discussion on Otsuka’s philosophy for introduction of new drugs, an update on the delamanid Phase III trial and paediatric development programme was provided.
Dr Charles Wells on behalf of Otsuka announced its “FighTBack Initiative” to enable access to delamanid for the management of MDR-TB patients. The plan is centred around a “20 by 2020” goal, which is to ensure delamanid reaches 20% of all diagnosed and treated MDR-TB patients in quality programmes by 2020. On top of its ongoing compassionate use (CU) and expanded access programmes, Otsuka intends to incorporate a targeted access donation program as a preliminary step to meet the community’s “Call to Action.” Discussions are ongoing with several stakeholders to supply delamanid in approximately 20 low and middle-income countries (half in the 27 highest-burden countries) starting in 2015. Other components of the plan include innovative research and development of new products for MDR-TB, optimized patient management, and collaborative capacity building, including working with communities using new approaches to ensure delamanid is administered safely and responsibly to minimize the threat of DR-TB.
Through the initiative, Otsuka anticipates that over 30 countries will have delamanid in routine use by the end of 2016. Discussions are ongoing to see whether delamanid can be made available through several other access channels including via GDF. Otsuka concluded by calling on the TB community to increase the development and availability of paediatric formulations for other MDR-TB medicines, help increase access for new TB drugs through advocacy for regulatory harmonization, and work together to strengthen pharmacovigilance systems for improved data collection and safety monitoring.
Call to action on the introduction of bedaquiline and delamanid
Grania Brigden (MSF − on behalf of 88 co-signatories)
SDRA approval of bedaquiline (Bdq) was granted in December 2012 and for delamanid (Dlm) in April 2014. WHO issued guidance on programmatic use of Bdq in June 2013 and for Dlm in November 2014. The WHO has been working with five early implementer countries for the introduction of new drugs for a year and the USAID donation programme for Bdq started in April 2015. Positive clinical experience with Bdq has been building from France, Georgia, Armenia, RSA, Latvia (CU programmes). All of this is offering hope to both patients and clinicians, but only 600 patients are on Bdq and less than 50 patients on delamanid outside of clinical trials. Delamanid as yet is only registered in the European Union, Japan, and South Korea. And there has been minimal use of repurposed companion Group 5 drugs needed to support introduction of new drugs. This slow uptake of the new drugs prompted MSF and 88 other civil society organizations to publish a public "Call to action" open letter on 10 March 2015 with a number of requests to industry and other stakeholders. A proposed solution is the establishment of an ‘action team’ comprised of actors committed to meet time-bound goals for increasing access to new and repurposed DR-TB drugs in 50 top high-burden countries through greater collaboration, coordination and accelerated activities i.e. DR-TB STAT!! (Scale-up Treatment Action Team). The time−bound goals are grouped under a number of broad headings including: "Quick start" with linked patient targets; optimal DR−TB treatment; regulatory status; procurement; and pharmacovigilance. Examples of previous similar collaborative mechanisms for expanding drug access were provided e.g. the collaboration between UNITAID and CHAI in relation to access to Paediatric ARVs. The speaker ended with posing a number of queries to the meeting, namely: can we achieve these targets; how can the key actors work together to ensure all patients requiring new drugs have access to them; what other barriers need to be addressed; and what actions need to be taken to achieve these goals within the next 6 months and 12 months? Success is to be measured by number of patients on treatment.
Philippe Duneton (UNITAID)
The meeting was reminded that the TB market is small and fragmented compared to that for HIV and Malaria, and that an integrated approach to diagnosis and treatment is needed. Scoping of the TB market and landscape shows that there is poor access to diagnosis (DST) and treatment of MDR-TB is complex, costly, and long. There is an urgent need for evidence to improve and simplify treatment, and to consolidate demand. Many countries have limited capacity for treatment and monitoring, whilst for the manufacturers, pharmacovigilance and reporting systems are often poorly established in low- and middle-income settings. Interventions are urgently needed to facilitate access. Projects by which UNITAID aims to support access to new TB medicines are: the endTB project with PIH, MSF and IRD (details of which were presented in session 7); the Strategic Rotating Stockpile via GDF, Stop TB Partnership (details of which were presented in session 3); and the Speeding Treatments to End Paediatric TB project (STEP TB) with the TB Alliance. Looking ahead, UNITAID has a strong interest in additional complementary approaches to increase the access to new TB drugs.
