Infectious diseases contribute to approximately 25% of global mortality and present critical healthcare challenges, especially in under-resourced countries. Recent research and development breakthroughs may help transform this situation. The industry is now leveraging novel analytical and bioinformatics technologies to better understand the biology and response to viral and bacteriological infections, and thereby develop more rapid and effective strategies for evaluating new therapeutic agents in clinical trials.
1. Applying lessons learned
Hepatitis C virus (HCV) therapeutics, frequently described as a breakthrough area in drug development, because it highlights the result of combining the biological understanding of disease and prioritizing appropriate resources to speed drug development. The first curative therapeutic regimens containing direct-acting agents for this important cause of liver disease were approved in 2011. Since then, seven additional regimens have received FDA approval with several more promising treatments currently in late stage clinical trials.
While many unique advances can be noted, HCV’s clinical success has also benefited from key lessons learned during the historical course of HIV drug development. As each HIV drug class developed sequentially, incremental advances were made. Based on the eventual success stories, drug companies began to appreciate the need to develop multi-drug combination regimens and co-formulations rather than individual agents, a strategy now applied to HCV and other infectious diseases.
Other notable triumphs included drugs with significantly fewer adverse side effects and more tolerable and convenient regimens that dramatically improved treatment adherence, such as one pill per day, rather than complicated dosing schedules.
2. Keeping pace with progress
In the past, research to support treatment for diseases like HIV infection required decades of development before realizing durable treatment successes in clinical settings. Now, with therapies addressing HCV and other viral and bacterial pathogens, development efforts are moving much more quickly within a condensed time frame.
Accelerated development promises to deliver therapies to the market faster, but it can present operational challenges. Robust, complex assays that address different virus and drug targets must be developed quickly to meet increasingly aggressive timelines and broader treatment portfolios. The ability to develop and provide comprehensive solutions that address a myriad of processes is crucial to successful drug development programs. Assays can evaluate drug potency, including the breadth of treatment efficacy, through the interrogation of specific genetic sequences, and susceptibility profiles of wild type viral and bacterial pathogens along with drug-resistant or vaccine escape variants.
3. Novel technological developments
Technology platforms, such as next-generation sequencing (NGS), provide new opportunities to meet the more aggressive demands of today’s drug development programs. Multiple NGS platforms exist, each with their own advantages, to better understand genetic variations and characterize drug resistance in microorganisms with much greater sensitivity.
These massive parallel sequencing technologies are advancing efforts to detect minor variant subpopulations, characterize host factor variability and improve the interrogation of heterogeneous target sequences (e.g., HIV-1 envelope), among many other applications. Coupled with potential cost efficiencies, increased throughput and quantitative assessments that enable objective assay interpretation, NGS will continue to propel rapid advances in the field.
Diagnostics and analyses of infectious diseases also depend on high-sensitivity measurements. Very low levels of a virus and viral replication can be detected and quantified with technologies such as ultra-sensitive protein detection methods and digital PCR, which offers increased sensitivity and absolute quantification of viral loads as compared to real-time PCR.
4. Improved microbial identification
Technical advances in clinical microbiology have also bolstered infectious disease development. Most notably, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has been employed for rapid identification of bacterial isolates. As part of the FDA submission data, MALDI-TOF can provide robust bacteria identification at the species level to support accurate interpretation of susceptibility results and strengthen downstream approval.
Other options for faster, more reliable results include 16s gene sequencing to identify and compare bacteria and multiplex PCR, which provides near real-time detection and quantification of bacteria. These precise and relatively low-cost methods will continue to enhance capabilities in microbiology research and clinical laboratories across the world.
5. Maintaining scientific and operational balance
While the emergence of novel technologies along with increased access to global patient populations will certainly generate new opportunities in infectious disease, important challenges to clinical trials support remain. From managing overall costs to maintaining strict operational oversight, a robust study management strategy must be in place to harness the full power of technologies while maximizing the return on investment. The proper balance of technology and resources remains a key consideration to make the most of clinical trial opportunities.
The future of infectious disease drug and vaccine development holds great promise. Pharmaceutical companies are exploring possibilities in many viral and bacterial targets, including Respiratory Viruses (influenza, RSV, HRV), Hepatitis viruses (HBV, HCV, HDV), Herpes viruses (CMV, HSV) and Hemorrhagic viruses (Ebola, Dengue), along with new HIV targets and antibiotics for drug-resistant disease strains.
Covance, the drug development business of Laboratory Corporation of America Holdings (LabCorp) and Monogram Biosciences, a member of LabCorp’s Specialty Testing Group are excited to make a difference in these advances and will continue to deliver dependable results across the continuum, from discovery and preclinical all the way to clinical and post-marketing.
Discover more about evaluating new antiviral and antibiotic drug candidates in our recent Infectious Disease eBook.
Hear more insights about recent infectious disease developments and clinical strategies from our recent webinar:
The Prescription for a Healthy Infectious Disease Clinical Trial: Rich Science & Seamless Operations.
Speakers: Chris Petropoulos, PhD, CSO, Monogram Biosciences and Vice President, LabCorp, and Pritty Patel, MS, MBA, Global Director Microbiology, Vaccines and Novel Immunotherapies, Covance Laboratories