Expert opinion on drug discovery
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Expert Opin Drug Discov · Jun 2015
ReviewAccessing external innovation in drug discovery and development.
A decline in the productivity of the pharmaceutical industry research and development (R&D) pipeline has highlighted the need to reconsider the classical strategies of drug discovery and development, which are based on internal resources, and to identify new means to improve the drug discovery process. Accepting that the combination of internal and external ideas can improve innovation, ways to access external innovation, that is, opening projects to external contributions, have recently been sought. ⋯ The buzz for accessing external innovation relies on the pharmaceutical industry's major challenge to improve R&D productivity, a conjuncture favorable to increase interactions with academia and new business models supporting access to external innovation. So far, access to external innovation has mostly been considered during early stages of drug development, and there is room for enhancement. First outcomes suggest that external innovation should become part of drug development in the long term. However, the balance between internal and external developments in drug discovery can vary largely depending on the company strategies.
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Expert Opin Drug Discov · Jan 2015
ReviewThe discovery and development of omalizumab for the treatment of asthma.
The evolution in immunological methods used to assess human allergic diseases has led to the identification of immunoglobulin E (IgE) as a diagnostic biomarker and a potential therapeutic target. Innovative technologies in molecular biology and immunogenetics contributed to the development of a selective blocking agent, disclosing new therapeutic perspectives in the treatment of allergic asthma. Omalizumab is the most advanced humanized anti-IgE monoclonal antibody that specifically binds serum-free IgE. Omalizumab also interrupts the allergic cascade by preventing binding of IgE with FcεRI receptors on mast cells, basophils, antigen-presenting cells and other inflammatory cells. ⋯ The clinical efficacy of omalizumab in allergic asthma has been well documented in clinical trials, involving adults, adolescents and children with moderate-to-severe and severe allergic asthma. To date, omalizumab has also been approved in chronic idiopathic urticaria for patients 12 years and older who remain symptomatic despite high dosages of H1 antihistamines. Omalizumab has also been investigated in many other different patient populations beyond allergic asthma and may yet have an application to other indications. While omalizumab is the only mAb available for treating allergic asthma, the authors anticipate that new mAbs will emerge in the future that overcome omalizumab's current limitations.
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Expert Opin Drug Discov · Jan 2015
ReviewAxitinib: from preclinical development to future clinical perspectives in renal cell carcinoma.
Based on extensive preclinical data and abundant evidence for clinical activity, vascular endothelial growth factor receptor (VEGFR) inhibitors are currently standard of care for metastatic renal cell carcinoma (mRCC). Axitinib is one of the most selective molecules in the class of anti-angiogenic agents, which confers an optimal profile between its safety and anti-cancer activity spectrum. ⋯ In 2015, axitinib has emerged as one of the major agents used in mRCC. Based on robust preclinical data, this highly specific VEGFR inhibitor continues to be evaluated in different indications, including the adjuvant setting but also sequential administration with other molecularly targeted agents or combinations with immune therapies.
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There is increasing evidence encouraging the development of drugs that positively modulate the γ-aminobutyric acid type B (GABA(B)) receptor for combating addiction. Compounds that target GABA(B) receptors are unique as anti-abuse therapies because of their impact against multiple addictive drugs. ⋯ Clinical data exist only for baclofen and mostly for alcohol use disorders. Additional trials are needed, but effects are promising. Whether PAMs, given alone or in combination with a direct GABA(B) receptor agonist, will be clinically effective and have fewer side effects requires investigation. The sedative effects of baclofen, a Food and Drug Administration (FDA)-approved drug, become less severe over time. Based on existing data, baclofen is well-tolerated. However, genetic and physiological differences are likely to contribute to individual responses to different therapeutic agents. The more immediate development of baclofen as a therapeutic for alcohol use disorders may be of significant benefit to some individuals.
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Chronic obstructive pulmonary disease (COPD) is a leading global cause of mortality and chronic morbidity. Inhalation of cigarette smoke is the principal risk factor for development of this disease. COPD is a progressive disease that is typically characterised by chronic pulmonary inflammation, mucus hypersecretion, airway remodelling and emphysema that collectively reduce lung function. There are currently no therapies that effectively halt or reverse disease progression. It is hoped that the development of animal models that develop the hallmark features of COPD, in a short time frame, will aid in the identifying and testing of new therapeutic approaches. ⋯ Recent advances in the field mark a point where animal models recapitulate the pathologies of COPD patients in a short time frame. They also reveal novel insights into the pathogenesis and potential treatment of this debilitating disease.