2016-10-14The growth of precision medicine presents challenges for the regulators of medicines, related to aspects that include the basis of evidence generation, patient involvement in the regulatory process, cost of new medicines and the need for new regulatory models. It also raises questions about the
2016-11-29Pivotal trials of Alkermes's antidepressant ALKS 5461 show how a patented clinical trial design might be able to help control problematic placebo responses.
2016-11-29Drug developers are still hunting for surrogate end points that can better capture the benefits of checkpoint inhibitors, oncolytic viruses and modified T cell therapies.
2016-11-29The FDA has approved Merck & Co's bezlotoxumab to reduce the recurrence of Clostridium difficile infection, marking the first approval for a new approach to the treatment of bacterial infections. Unlike antibiotics, which kill pathogenic bacteria, bezlotoxumab is an antibody that mops up toxins
2016-11-29Promising phase II data from The Medicines Company's inclisiran have paved the way for phase III trials of a long-acting oligonucleotide-based PCSK9 inhibitor. Although the FDA has already approved two PCSK9 blockers — Amgen's evolocumab and Sanofi and Regeneron's alirocumab — these subcutaneously delivered lipid-lowering
2016-11-29European regulators have started publishing the full clinical trial reports for drugs that are approved for use in the European Union. Results can be accessed at https://clinicaldata.ema.europa.eu/web/cdp/home.As Nature Reviews Drug Discovery went to press, the agency had released data for only two
2016-11-29Drug companies are getting moderately better at enabling access to drugs for people in low- and middle-income countries shows a recent report from the non-profit Access to Medicine Foundation.GlaxoSmithKline topped the biennial ranking, for the 5th consecutive time, followed by Johnson & Johnson
2016-11-18There is a severe innovation gap in antibiotic R&D, and the field faces two daunting challenges. First, the discovery of novel antibiotics with no pre-existing cross- and co-resistance, and with a very low potential for emergence of resistance, presents considerable scientific obstacles, especially for Gram-negative
2016-11-29Drug development for central nervous system (CNS) disorders is challenging, and a higher attrition rate compared with non-CNS drugs has been reported (Nat. Rev. Drug Discov.14, 815–816; 2015). With the aim of improving the understanding of these challenges, we analysed the
2016-11-29More than 98% of the Alzheimer disease candidates that make it into phase III trials subsequently fail, according to a 2014 review of the field. Failure rates for Parkinson disease and amyotrophic lateral sclerosis (ALS) drug candidates are similarly dire. And yet, the 1.5-year-old biotechnology company Denali Therapeutics has already raised a massive US$349 million to tackle these and other neurodegenerative diseases. The company is about to advance its first candidate into the clinic, and Chief Medical Officer Carole Ho, former vice-president of early clinical development at Genentech, is making plans. She tells Asher Mullard that genetic insights into the biology of neurodegenerative disease could provide new therapeutics within 10 years.
2016-11-04This article analyses recent data on the reported causes of drug candidate attrition, which indicate that lack of efficacy is the reason for approximately half of all phase II and phase III failures.
2016-11-29Chimeric antigen receptor (CAR) T cells are a promising type of cancer immunotherapy in which T cells are engineered to express receptors for tumour-specific antigens, thereby unleashing a cytotoxic immune response against cancer cells. However, the effect of such treatment is limited to the natural
2016-11-29Over 80% of colorectal cancers (CRCs) contain mutations in adenomatous polyposis coli (APC), and more than 90% of these mutations result in the production of truncated proteins. Using a small-molecule screen, Zhang and colleagues have now identified a compound that selectively kills cells
2016-11-29The pro-survival protein myeloid cell leukaemia 1 (MCL1) is overexpressed in many different types of cancer, but development of small molecule inhibitors for this protein has been challenging. Now, reporting in Nature, Olivier Geneste and colleagues describe a highly specific and potent small molecule
2016-11-18Dyslipidaemia, the elevation of plasma cholesterol and/or triglycerides, is a central risk factor for metabolic syndrome and can lead to insulin resistance, fatty liver and atherosclerosis. Although therapies exist to treat these conditions, such agents are often associated with side effects, and drug combinations are
2016-11-18The complement system is a key component of the innate immune system, which constitutes an effective first line of defence against invading pathogens. However, inappropriate or uncontrolled complement activation can be deleterious and has been implicated in various diseases. Now, writing in Nature Chemical Biology
2016-11-18Neutrophil extracellular traps (NETs), made of processed chromatin bound to cytotoxic enzymes, are released by neutrophils into the extracellular space to control microbial infections. However, NETs have also been implicated in cancer metastasis. Here, Park et al. observe NET formation in a mouse model
2016-11-18New antibiotics are urgently needed to tackle the growing problem of drug resistance. To identify potential novel antimicrobials, Chu et al. have deployed bioinformatic modelling and chemical synthesis to generate natural product structures from gene clusters that are predicted to encode non-ribosomal peptides (complex
2016-11-18Antiretroviral therapy (ART) effectively suppresses HIV replication; however, lifelong treatment is associated with toxicity and, once ART is withdrawn, the virus rebounds. Persistent viral reservoirs form rapidly during acute HIV infection owing to high levels of viral replication in gastrointestinal tissues (GITs) and severe depletion
2016-11-18Cannabinoid receptor 1 (CB1) represents a promising therapeutic target for a wide range of disorders. However, the molecular details that define the binding modes of both endogenous and pharmacological ligands have remained poorly understood. Now, Hua et al. have solved the crystal structure of
2016-10-07HIV-1 is a retrovirus that integrates into host chromatin and can remain transcriptionally quiescent in a pool of immune cells. This characteristic enables HIV-1 to evade both host immune responses and antiretroviral drugs, leading to persistent infection. Upon reactivation of proviral gene expression, HIV-1 envelope
2016-10-21Immune-mediated diseases are clinically heterogeneous but they share genetic and pathogenic mechanisms. These diseases may develop from the interplay of genetic factors and environmental or lifestyle factors. Exposure to such factors, including infectious agents, is associated with coordinated changes in gene transcription owing to epigenetic
2016-11-11Calpains are a family of proteases that were scientifically recognized earlier than proteasomes and caspases, but remain enigmatic. However, they are known to participate in a multitude of physiological and pathological processes, performing 'limited proteolysis' whereby they do not destroy but rather modulate the functions