Drug Discovery and Development

Drug discovery involves the exploration and analysis of various compounds that can enhance the well-being of patients and contribute to their improved quality of life by addressing disease symptoms or progression. The drug development timeline spans several years and can be plagued with failures and large resource expenditures. However, there is also a great deal of learning that happens at each stage along the drug development timeline. This learning ensures that drug developers and drug manufacturers are bringing to market the right compounds, also called small molecules, with the correct safety profiles that will benefit the intended patient population.

Our drug development overview encompasses the entire journey of identifying, researching and refining potential drug candidates. We touch on considerations for preclinical studies, clinical trials, regulatory approval and post-marketing surveillance that are important to bring safe and effective medications to market.

Stages of Drug Discovery and Development Process

• Target identification: The drug development process starts with target identification, which is the process of identifying and characterizing specific molecules, peptides, proteins, genetic mutations, or other biological anomalies responsible for disease or symptom manifestation.
• Target validation: Target validation is the procedure of substantiating and assessing the therapeutic significance and potential of a distinct target through experimentation. Modulating the activity of the target must confirm therapeutic benefit.
• The hit discovery process: This phase of drug development involves screening large compound libraries or utilizing computational methods to identify potential hits (the compounds that exhibit the desired activity at the drug target).
• Assay development: Assays, in the pharmaceutical industry and clinical development process, are analytical procedures utilized in drug discovery and development to evaluate a compound’s impact qualitatively and quantitatively on disease targets and to understand the safety profile.
• Hit-to-lead phase: Promising hits are further optimized and prioritized based on desired properties, such as potency, to identify lead compounds with higher potential for development into drug candidates.
• Lead optimization phase: It is a critical stage in the drug discovery process where lead compounds are systematically modified and refined to improve their properties, such as potency, safety, and selectivity, to identify a candidate molecule with optimal pharmaceutical characteristics for further development.
• Preclinical development: This stage of drug development involves extensive pharmacokinetic studies in animal models to evaluate the safety, efficacy and ADME (absorption, distribution, metabolism, excretion) profiles of potential drug candidates. In vitro experiments are also utilized in the form of cell-based assays. During preclinical development, key bioactivity data is obtained that will inform the design of clinical trials and in the preparation of regulatory filings. At this stage, the number of small molecules has been reduced to only the top candidate as resources and expenses can be a challenge for drug developers.
• Submission of IND: The submission of an Investigational New Drug (IND) application to regulatory authorities is a crucial step in the drug development regulatory process. The submission allows the initiation of clinical trials by providing comprehensive data on the compound's preclinical studies, safety and suggested clinical investigation plan. From this point forward, drug developers are in constant communication with regulatory authorities.
• Clinical studies & submission of NDA: The drug development process involves drug characterization to understand small molecule drug properties and behavior, pharmacokinetics, pharmacodynamics and overall therapeutic profile. Following drug characterization, the process progresses to clinical trials, conducted in sequential phases. Phase 1 trials involve a small group of healthy volunteers and focus on assessing the drug's safety, optimal dosage and pharmacokinetics. In Phase 2 trials, the study population expands to a larger group of patients to evaluate the drug's efficacy in treating the targeted disease. Phase 3 trials involve an even larger patient population, confirming the drug's effectiveness and monitoring adverse reactions more comprehensively. Once these clinical trials are successfully completed, the process advances to the submission of a New Drug Application (NDA) to regulatory authorities. The NDA includes comprehensive data on preclinical and clinical studies, safety profiles and proposed clinical investigation plans. Following regulatory review and approval, the drug enters Phase 4, which involves post-marketing surveillance to gather additional data on long-term safety and effectiveness. Collectively, these stages contribute to the time to market for a new drug, ensuring its safety and efficacy for patients.

Trends in Pharmaceutical Small Molecule R&D

Recent trends in pharmaceutical R&D drug development include:

An increased focus on precision medicine and targeted therapies

Precision medicine has revolutionized the relationship between genomics and drug development. Identifying disease root cause informs on targeted treatments. Effective personalized therapies have the potential to replace the 'one-size-fits-all' approach.

For instance, two primary methods for precise cancer targeting are disrupting essential cancer cell pathways - pathway-based therapy and modulating the patient's immune system to fight cancer (immunotherapy). PARP inhibitors offer a new option for ovarian cancer treatment by inducing synthetic lethality in tumor cells with BRCA1 or BRCA2 mutations.

In another example of precision medicine and targeted therapies, large-scale sequencing studies of epileptic encephalopathies have revealed new causative genes related to ion channels and cell signaling, creating opportunities for drug screening using various model systems and assays. Research on KCNT1 mutations associated with certain epilepsy types found that the drug quinidine, approved for cardiac arrhythmias, can block KCNT1 channels, suggesting a potential therapeutic avenue.

Utilizing artificial intelligence and machine learning in the drug product development process

Artificial intelligence has the potential to accelerate the drug discovery workflow. However, companies must embrace a mindset shift for this to be realized, adopting automated and efficient AI-driven processes. The focus must shift to delivering tangible value to patients and the scientific process in shorter timeframes.

Reimagining drug design and discovery with computational biology entails leveraging transformative AI platforms to accelerate the discovery of medicines, utilizing advanced computational techniques to analyze and optimize molecules. These solutions, including GPU-accelerated drug discovery and generative AI, offer promising avenues to accelerate various phases of the drug development pathway, enabling faster and more efficient development of new therapies.

An emphasis on expedited regulatory pathways for rare diseases and unmet medical needs

The process of developing new drugs is complex and challenging, often leading to lengthy timelines. To expedite patient access to treatments, especially for serious and life-threatening diseases with unmet medical needs, regulatory authorities have implemented pathways to accelerate drug development and approval. Some key pathways include orphan drug designation, accelerated approval, priority review, conditional approvals for drugs with promising early-stage data and post-marketing commitments, etc.

It is anticipated that additional options for regulatory acceleration will emerge in the future, focusing on collaborative work-sharing like the Access consortium and Orbis, building upon existing pathways and revising current tools. Moreover, advancements in data management have the potential to further reduce regulatory review timelines without compromising the scientific rigor of regulatory assessments.

FAQs

What is drug discovery and development process?

Drug discovery and development refer to the systematic process of identifying and designing potential new drugs, conducting preclinical and clinical studies to evaluate their safety and efficacy, obtaining regulatory approvals and ultimately bringing these drugs to market for treating diseases.

What are some factors that influence spending for R&D in drug discovery and development?

• Technological advancements
• Regulatory requirements
• Market competition
• Scientific complexity
• Intellectual property protection
• Market potential
• Government funding
• Economic conditions

Which part of the drug discovery life cycle does quantum computing affect?

Quantum computing has the potential to impact multiple stages of the drug discovery life cycle, including molecular modeling and simulation, optimization of chemical reactions, analysis of complex biological systems and accelerating the process of screening and designing novel drug candidates.

How is bioinformatics used in drug discovery?

Bioinformatics plays a crucial role in various stages of the drug development cycle, including target identification, hit discovery, lead optimization and preclinical testing. Bioinformatics utilizes computational analysis and modeling to analyze large-scale biological data. Bioinformatics with the addition of data science can inform on protein structures, simulate drug-target interactions, identify potential drug candidates and optimize their properties.

What is a lead compound in drug discovery?

A lead compound in drug discovery is a candidate that exhibits favorable biological activity against a specific target, serving as a starting point for further optimization and development.

recent-articles