Commercial viability of CNS drugs: Balancing the risk/reward profile

Johnson, G.

doi:10.1016/j.nbd.2013.10.004

Cited by 3 publications

(5 citation statements)

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“…The late stage (Phase II, Phase III) attrition rate of CNS drug-candidates is known to be particularly high, mainly due to lack of efficacy (or safety issues). ,,, The successful development of CNS drugs relies on the development of appropriate animal models for efficacy testing in preclinical studies and a new paradigm for drug development that will give early readouts for proof of concept in order to allow attrition to occur much earlier in the process. , This challenge applies to PD drug discovery, especially for the development of antidyskinetic drugs . To date, the MPTP-treated NHP is considered the most predictive animal model of LID. ,, Indeed, after chronic treatment with L-dopa, MPTP-treated monkeys develop choreic and dystonic movements that can be scored using clinical rating scales after only modest adaptations .…”

Section: Results and Discussionmentioning

confidence: 99%

“…Many companies are trying to reduce costs by outsourcing drug discovery to academic laboratories or contract research organizations due to unfavorable risk/reward balance with CNS drug development. ,− These new partners need to develop standardized and accessible tools for CNS drug discovery. Increasing confidence in preclinical data during the development of antidyskinetic agents is of crucial importance.…”

Section: Results and Discussionmentioning

confidence: 99%

“…The late stage (Phase II, Phase III) attrition rate of CNS drug-candidates is known to be particularly high, mainly due to lack of efficacy (or safety issues). 12,13,23,24 The successful development of CNS drugs relies on the development of appropriate animal models for efficacy testing in preclinical studies and a new paradigm for drug development that will give early readouts for proof of concept in order to allow attrition to occur much earlier in the process. 12,13 This challenge applies to PD drug discovery, especially for the development of antidyskinetic drugs.…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

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Validation of a New Scoring Scale for Behavioral Assessment of L-Dopa-Induced Dyskinesia in the Rat: A New Tool for Early Decision-Making in Drug Development

Loiodice¹,

Denibaud²,

Deffains³

et al. 2017

ACS Chem. Neurosci.

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The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated non-human primate (NHP) has been described as the most translatable model for experimental reproduction of L-dopa-induced dyskinesia (LID). However, from a drug discovery perspective, the risk associated with investment in this type of model is high due to the time and cost. The 6-hydroxydopamine (6-OHDA) rat dyskinesia model is recommended for testing compounds but relies on onerous, and non-standard behavioral rating scales. We sought to develop a simplified and sensitive method aiming at assessing LID in the rat. The purpose was to validate a reliable tool providing earlier insight into the antidyskinetic potential of compounds in a time/cost-effective manner before further investigation in NHP models.Unilaterally 6-OHDA-lesioned rats were administered L-dopa (20 mg/kg) and benserazide (5 mg/kg) daily for 3 weeks starting 4 weeks post-lesion, then co-administered with amantadine (20-30-40 mg/kg). An adapted rating scale was used to score LID frequency and a severity coefficient was applied depending on the features of the observed behavior.A gradual increase (about 3-fold) in LID score was observed over the 3 weeks of L-dopa treatment.The rating scale was sensitive enough to highlight a dose-dependent amantadine-mediated decrease (about 2.2-fold) in LID score.We validated a simplified method, able to reflect different levels of severity in the assessment of LID and, thus, provide a reliable tool for drug discovery.

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Section: Results and Discussionmentioning

confidence: 99%

Section: Results and Discussionmentioning

confidence: 99%

Section: Acs Chemical Neurosciencementioning

confidence: 99%

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Validation of a New Scoring Scale for Behavioral Assessment of L-Dopa-Induced Dyskinesia in the Rat: A New Tool for Early Decision-Making in Drug Development

Loiodice¹,

Denibaud²,

Deffains³

et al. 2017

ACS Chem. Neurosci.

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“…There are many reasons why pharmaceutical companies have left the field of the neurosciences [16,42]. This withdrawal from research leaves the door open ''to rethink how academia and industry can work together for the public good'' [12].…”

Section: Towards a New Organization Of Drug Researchmentioning

confidence: 99%

“…In line with this, pharmaceutical companies are aware that drugs targeting the main neuropsychiatric disorders are exposed to scientific, clinical and commercial risk. They are now turning to orphan diseases such as amyotrophic lateral sclerosis instead of Alzheimer or Parkinson disease [16].…”

Section: Introductionmentioning

confidence: 99%

In search of innovative therapeutics for neuropsychiatric disorders: The case of neurodegenerative diseases

Hirsch

2015

Annales Pharmaceutiques Françaises

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The recent medical literature highlights the lack of new drugs able to prevent or treat neurodegenerative diseases such as Alzheimer disease or Parkinson disease. Yet, the prevalence of these diseases is growing, related to increasing life expectancy, and is leading to a rise in their economic and social cost. At the same time, pharmaceutical companies are reducing or halting their investment in neuropharmacological research. Why have advances in basic neuroscience and our understanding of these diseases not allowed innovative discoveries in drug research? This review will try to explain this failure and suggest possible solutions: develop basic and clinical research but with the emphasis on translational and truly collaborative research; improve preclinical studies by developing more appropriate animal models, using new biomarkers and methodologies such as imaging suitable for clinical trials, providing worthwhile information on the ability of the drug to reach its intended target and induce significant pharmacological changes; build a new system of research management, based on stronger interdisciplinary relations between preclinical and clinical research and including the introduction of international precompetitive research between academic teams, start-up companies and pharmaceutical laboratories; hold early discussions with the regulatory authorities during preclinical studies and at the beginning of clinical trials in order to validate the methodological approaches; involve patients' associations in this new organization of research. These changes should help to ensure the discovery of effective treatments for these pathologies.

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Medications development for substance-use disorders: contextual influences (dis)incentivizing pharmaceutical-industry positioning

Janero

2014

Expert Opinion on Drug Discovery

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Given the well-entrenched business stance whereby the prospect of future profits in major markets largely determines drug-company R&D investment trajectory, strategic initiatives offering substantial reductions in the risks and opportunity (i.e., time and money) costs associated with SUD drug discovery are likely to be the most potent drivers for encouraging mainstream industry positioning in this therapeutic area. Such initiatives could originate from front-loaded R&D operational and back-loaded patent, regulatory, marketing and health-care policy reforms. These may be too involved and protracted for the turbulent pharmaceutical industry to entertain amid its recent retrenchment from psychiatric/CNS diseases and intense pressures to increase productivity and shareholder value.

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Commercial viability of CNS drugs: Balancing the risk/reward profile

Cited by 3 publications

References 1 publication

Validation of a New Scoring Scale for Behavioral Assessment of L-Dopa-Induced Dyskinesia in the Rat: A New Tool for Early Decision-Making in Drug Development

Validation of a New Scoring Scale for Behavioral Assessment of L-Dopa-Induced Dyskinesia in the Rat: A New Tool for Early Decision-Making in Drug Development

In search of innovative therapeutics for neuropsychiatric disorders: The case of neurodegenerative diseases

Medications development for substance-use disorders: contextual influences (dis)incentivizing pharmaceutical-industry positioning

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