Voluntary licensing of long-acting HIV prevention and treatment regimens: using a proven collaboration- and competition-based mechanism to rapidly expand at-scale, sustainable, quality-assured and affordable supplies in LMICs.

INTRODUCTION: Emerging long-acting (LA) prevention and treatment medicines, technologies and regimens could be game-changing for the HIV response, helping reach the ambitious goal of halting the epidemic by 2030. To attain this goal, the rapid expansion of at-scale, sustainable, quality-assured, and affordable supplies of LA HIV prevention and treatment products through accelerated and stronger competition, involving both originator and generic companies, will be essential. To do this, global health stakeholders should take advantage of voluntary licensing of intellectual property (IP) rights, such as through the United Nations-backed, not-for-profit Medicines Patent Pool, as a proven mechanism to support broad access to existing HIV medicines across low- and middle-income countries (LMICs). DISCUSSION: While voluntary licensing may unlock the possibility for generic competition to take place ahead of patent expiry, there are additional elements-of amplified importance for more complex LA HIV medicines-that need to be taken into consideration. This paper discusses 10 enablers of voluntary licensing of IP rights as a model to rapidly expand at-scale, sustainable, quality-assured, and affordable supplies of LA HIV prevention and treatment regimens in LMICs: Identifying promising LA technology platforms and drug formulations at an early developmental stage and engaging with patent holders Consolidating a multidisciplinary network and strengthening early-stage coordination and collaboration to foster innovation Embedding public health considerations in product design and delivery Building innovative partnerships for product development and commercialization Raising awareness of and creating demand for emerging LA products Estimating the market size, ensuring sufficient competition and protecting sustainability Using technology transfer and hands-on technical support to reduce product development timelines and costs Exploring de-risking mechanisms and financial incentives to support generic manufacturers Optimizing strategies for generic product development and regulatory filings Aligning and coordinating efforts of stakeholders across the value chain. CONCLUSIONS: Rapid access to emerging LA prevention and treatment regimens and technologies can be facilitated by voluntary licensing-catalyzed and supplemented by enabling collaborative and non-duplicative efforts of various other stakeholders. This can effectively lead to improved-accelerated and cheaper-access to quality-assured medicines for populations in LMICs.

Expanding access to biotherapeutics in low-income and middle-income countries through public health non-exclusive voluntary intellectual property licensing: considerations, requirements, and opportunities.

Biotherapeutics, such as recombinant proteins and monoclonal antibodies, have become mainstays of modern medicine as shown by their increasing number in the WHO Model List of Essential Medicines. However, despite frequently offering clinical advantages over standards of care, they remain largely out of reach for populations in low-income and middle-income countries (LMICs), partly because of high costs. Accordingly, the WHO Model List of Essential Medicines Expert Committee has requested that the Medicines Patent Pool explore intellectual property licensing to address this challenge. We therefore investigated how licensing could successfully improve affordability of and timely access to biotherapeutics in LMICs, by leveraging expert consultations, literature analysis, and internal technical knowledge. The key elements identified as relevant to support access to affordable biosimilars in LMICs through licensing include: prioritising potential biotherapeutic targets according to their potential for public health impact; supporting biosimilar product and clinical development (including through technology transfer to expedite regulatory approval); and facilitating biosimilars' entry and use in LMICs (by meeting procurement, supply chain, and health system requirements).

The economic and public health impact of intellectual property licensing of medicines for low-income and middle-income countries: a modelling study.

BACKGROUND: Non-exclusive voluntary licensing that is access-oriented has been suggested as an option to increase access to medicines to address the COVID-19 pandemic. To date, there has been little research on the effect of licensing, mainly focused on economic and supply chain considerations, and not on the benefits in terms of health outcomes. We aimed to study the economic and health effect of voluntary licensing for medicines for HIV and hepatitis C virus (HCV) in low-income and middle-income countries (LMICs). METHODS: A robust modelling framework was created to examine the difference between scenarios, with (factual) and without (counterfactual) a Medicines Patent Pool (MPP) licence for two medicines, dolutegravir and daclatasvir. Data were obtained from MPP licensees, as well as a large number of external sources. The primary outcomes were the cost savings and health impact between scenarios with and without MPP licences across all LMICs. Through its licences, MPP had access to the volumes and prices of licensed generic products sold in all covered countries on a quarterly basis. These data informed the volumes, prices, and uptake for the past factual scenarios and were the basis for modelling the future factual scenarios. These scenarios were then compared with a set of counterfactual scenarios in the absence of the studied licences. FINDINGS: Cumulatively, between 2017 and 2032, the model's central assumptions predicted an additional uptake of 15·494 (range 14·406-15·494) million patient-years of dolutegravir-based HIV treatments, 151 839 (34 575-312 973) deaths averted, and US$3·074 (1·837-5·617) billion saved through the MPP licence compared with the counterfactual scenario. For daclatasvir-based HCV treatments, the cumulative effect from 2015 to 2026 was predicted to be an additional uptake of 428 244 (127 584-636 270) patients treated with daclatasvir, 4070 (225-6323) deaths averted, and $107·593 (30·377-121·284) million saved with the licence compared with the counterfactual scenario. INTERPRETATION: The chain of effects linking upstream licensing to downstream outcomes can be modelled. Accordingly, credible quantitative estimates of economic and health effects arising from access-oriented voluntary licensing were obtained based on assumptions that early generic competition leads to price reductions that influence procurement decisions and enable the faster and broader uptake of recommended medicines, with beneficial economic and health effects. FUNDING: Unitaid.

NOACs Added to WHO's Essential Medicines List: Recommendations for Future Policy Actions.

The introduction of non-vitamin K antagonists oral anticoagulants, a class of medicines which includes dabigatran, apixaban, edoxaban and rivaroxaban, has resulted in improvements in the safety and efficacy of non valvular atrial fibrillation treatment for stroke prevention, with significant reductions in stroke, intracranial haemorrhage, and mortality. For these reasons, a team of World Heart Federation Emerging Leaders led efforts to add non-vitamin K antagonists oral anticoagulants to the World Health Organization's Model List of Essential Medicines in 2019. Following the inclusion of this class of medicines in the Essential Medicines List, this editorial proposes several recommendations to improve the accessibility, affordability and acceptability of non-vitamin K oral anticoagulants, especially in low- and middle-income settings, in order to successfully manage non-valvular atrial fibrillation and to lower the risk of stroke.

Access to Treatment for Hepatitis B Virus Infection - Worldwide, 2016.

Worldwide, an estimated 257 million persons are living with chronic hepatitis B virus (HBV) infection (1). To achieve the World Health Organization (WHO) goals for elimination of HBV infection worldwide by 2030, defined by WHO as 90% reduction in incidence and 65% reduction in mortality, access to treatment will be crucial. WHO estimated the care cascade* for HBV infection, globally and by WHO Region. The patent and licensing status of entecavir and tenofovir, two WHO-recommended medicines for HBV treatment, were examined using the Medicines Patent Pool MedsPaL† database. The international price of tenofovir was estimated using WHO's global price reporting mechanism (GPRM), and for entecavir from a published study (2). In 2016, among the estimated 257 million persons infected with HBV worldwide, approximately 27 million (10.5%) were aware of their infection, an estimated 4.5 million (16.7%) of whom were on treatment. In 2017, all low- and middle-income countries (LMICs) could legally procure generic entecavir, and all but two LMICs could legally procure generic tenofovir. The median price of WHO-prequalified generic tenofovir on the international market fell from $208 per year in 2004 to $32 per year in 2016. In 2015, the lowest reported price of entecavir was $427 per year of treatment (2). Increased availability of generic antivirals effective in treating chronic HBV infection has likely improved access to treatment. Taking advantage of reductions in price of antivirals active against HBV infection could further increase access to treatment. Regular analysis of the hepatitis B treatment care cascade can assist in monitoring progress toward HBV elimination goals.