A public-private partnership for the express development of antiviral leads: a perspective view.

INTRODUCTION: The COVID-19 pandemic raises the question of strategic readiness for emergent pathogens. The current case illustrates that the cost of inaction can be higher in the future. The perspective article proposes a dedicated, government-sponsored agency developing anti-viral leads against all potentially dangerous pathogen species. AREAS COVERED: The author explores the methods of computational drug screening and in-silico synthesis and proposes a specialized government-sponsored agency focusing on leads and functioning in collaboration with a network of labs, pharma, biotech firms, and academia, in order to test each lead against multiple viral species. The agency will employ artificial intelligence and machine learning tools to cut the costs further. The algorithms are expected to receive continuous feedback from the network of partners conducting the tests. EXPERT OPINION: The author proposes a bionic principle, emulating antibody response by producing a combinatorial diversity of high q uality generic antiviral leads, suitable for multiple potentially emerging species. The availability of multiple pre-tested agents and an even greater number of combinations would reduce the impact of the next outbreak. The methodologies developed in this effort are likely to find utility in the design of chronic disease therapeutics.

Preclinical Alzheimer Disease Drug Development: Early Considerations Based on Phase 3 Clinical Trials.

The number of people in the United States living with Alzheimer disease (AD) is growing, resulting in significant clinical and economic impact. Substantial research investment has led to drug development in stages of AD before symptomatic dementia, such as preclinical AD. Although there are no treatments approved for preclinical AD, there are currently 6 phase 3 clinical trials for preclinical AD treatments. In this article, we review these clinical trials and highlight considerations for future coverage decisions. In line with the definition of preclinical AD, enrollment in these trials focuses on cognitively unimpaired patients that are at high risk of AD because of family history and then genetic testing or brain imaging. Enrollment in most of these trials also allows for younger patients, including those aged under 65 years. Primary clinical trial endpoints focus on cognition often 4 or more years after treatment. Secondary endpoints include other measures of cognition and function, as well as biomarkers. Review of these trials brings to light a few potential considerations when covering these new medications in the future. First, novel and potentially costly approaches involving genetic testing and/or positron emission tomography imaging may be needed to identify appropriate patients and should be developed efficiently. Second, the long duration of these clinical trials suggest that there may be a need for alternative payment approaches in the United States that encourage early payers to pay for a medication for which the long-term benefits may not be realized until after the beneficiary is no longer with the health plan. Third, the value of AD treatments may differ across populations, creating a potential role for indication-based or population-based contracting. Finally, considering the potentially high budgetary impact and little real-world evidence for a new drug class, payers and manufacturers may want to consider outcomes-based payment approaches and coverage with evidence development to mitigate uncertainty about the value of the treatment demonstrated in well-defined populations in clinical trials versus more heterogeneous real-world settings. DISCLOSURES: This work was funded through a generous gift from the Global CEO Initiative on Alzheimer Disease. Hung reports grants from Agency for Healthcare Research and Quality and Pharmaceutical Research and Manufacturers of America outside the submitted work and past employment at CVS Health and BlueCross BlueShield Association. McClellan is an independent board member on the boards of Johnson & Johnson, Cigna, Alignment Healthcare, and Seer; co-chairs the Accountable Care Learning Collaborative and the Guiding Committee for the Health Care Payment Learning and Action Network; and receives fees for serving as an advisor for Cota and MITRE. Hamilton Lopez and Schneider have nothing to disclose. Part of this work was presented at the 2019 AMCP Nexus Meeting, October 29-November 1, 2019, in National Harbor, MD.

Benchmarking biopharmaceutical process development and manufacturing cost contributions to R&D.

This study aims to benchmark and analyze the process development and manufacturing costs across the biopharmaceutical drug development cycle and their contribution to overall research and development (R&D) costs. This was achieved with a biopharmaceutical drug development lifecycle cost model that captured the costs, durations, risks and interdependencies of the clinical, process development and manufacturing activities. The budgets needed for process development and manufacturing at each phase of development to ensure a market success each year were estimated. The impact of different clinical success rate profiles on the process development and manufacturing costs at each stage was investigated, with a particular focus on monoclonal antibodies. To ensure a market success each year with an overall clinical success rate (Phase I to approval) of ~12%, the model predicted that a biopharmaceutical company needs to allocate process development and manufacturing budgets in the order of ~$60 M for pre-clinical to Phase II material preparation and ~$70 M for Phase III to regulatory review material preparation. For lower overall clinical success rates of ~4%, which are more indicative of diseases such as Alzheimer's, these values increase to ~$190 M for early-phase and ~$140 Mfor late-phase material preparation; hence, the costs increase 2.5 fold. The costs for process development and manufacturing per market success were predicted to represent 13-17% of the R&D budget from pre-clinical trials to approval. The results of this quantitative structured cost study can be used to aid decision-making during portfolio management and budget planning procedures in biopharmaceutical development.

[Developability assessment with case studies highlighting the decision taking]. / Exemples d'études de développabilité apportant un éclairage à la prise de décision.

Therapeutic antibodies generation has to be faster with less development costs. This requires combination of in silico predictions associated with cutting edge screening and characterization technologies. Here, non-exhaustive examples illustrate this simultaneity need.

TITLE: Exemples d'études de développabilité apportant un éclairage à la prise de décision. ABSTRACT: De nos jours, la génération d'anticorps thérapeutiques doit être plus rapide avec des coûts de développement moins importants. Pour cela, des prédictions in silico sont associées à des technologies de criblage et de caractérisation de pointe. Les exemples choisis ici sont non-exhaustifs mais illustrent ce besoin de travailler en parallèle.

Lessons learned from Ebola Vaccine R&D during a public health emergency.

In spite of a complete lack of Research and Development (R&D) preparedness, the 2013-2016 West-Africa Ebola experience demonstrated that it is possible to compress R&D timelines to less than a single year, from a more usual decade or longer. This is mostly to be credited to an unprecedented collaborative effort building on the availability of a small number of candidate diagnostic tests, drugs and vaccines that could be moved rapidly into the clinical phase evaluation. The World Health Organization (WHO) led international consultations and activities - including the organization of a successful Ebola vaccine efficacy trial in Guinea - as a contribution to the unprecedented global efforts to control the Ebola epidemic. Since 2015, WHO expert teams and partners are implementing a novel R&D model for emerging infectious pathogens which are the most likely to cause severe outbreaks in the future, and for which no or only few medical countermeasures are available: the WHO R&D Blueprint. The objective for the Blueprint is the fostering of a R&D environment which is prepared for quickly and effectively responding to outbreaks due to emerging infectious disease.