Drug Discovery

Drug discovery and the subsequent path to market is a complex, lengthy, and expensive process that often spans over a decade and costs billions of dollars. It requires a coordinated effort among biologists, chemists, pharmacologists, clinicians, and various other experts. Here’s a step-by-step breakdown of the process:

  1. Target Identification and Validation:
    1. Target Identification: Researchers identify a molecule or pathway (often a protein) involved in the disease condition, which could be targeted to alter the disease course.
    2. Target Validation: Scientists ensure that the identified target is indeed involved in the disease progression and that modulating its activity will have a therapeutic effect.
  2. Lead Compound Identification and Optimization:
    1. High-Throughput Screening: Thousands to millions of compounds are quickly tested for activity against the identified target. This often uses robotic systems.
    2. Lead Compound Identification: Compounds that show promise from the initial screening are termed ‘lead compounds’.
    3. Lead Optimization: Chemists modify these lead compounds to enhance their therapeutic properties and reduce side effects, yielding ‘drug candidates’.
  3. Preclinical Testing:
    1. In Vitro Testing: Drug candidates are tested on cells in a laboratory to determine their biological activity.
    2. In Vivo Testing: The drug candidates are tested in animals to study their safety profile, pharmacodynamics (what the drug does to the body), and pharmacokinetics (what the body does to the drug).
  4. Clinical Trials:
    1. Phase 1: Tests the drug on a small group of healthy volunteers (20-100) to evaluate its safety, dosage range, and side effects.
    2. Phase 2: Evaluates the drug’s effectiveness and further examines its safety in a larger group of patients (100-300).
    3. Phase 3: Assesses the drug’s efficacy and monitors side effects in a larger cohort of patients (1,000-3,000) compared to current standard treatments.
  5. Regulatory Submission:
    1. After successful Phase 3 trials, a New Drug Application (NDA) or Biologics License Application (BLA) is submitted to the regulatory agency, like the FDA in the U.S. The agency reviews the entire data set for the drug: from its discovery to preclinical data to clinical trial results.
  6. Market Approval:
    1. If the regulatory agency is convinced of the drug’s safety and efficacy, they grant approval for the drug to be marketed to the public.
  7. Post-Marketing Surveillance/Phase 4:
    1. After market approval, the drug is monitored in the general population to catch any rare side effects that might not have been observed in clinical trials.
    2. Trials might also compare the drug to competitors, explore additional use cases, or determine the long-term effectiveness and cost-effectiveness.
  8. Pharmacovigilance:
    1. Continual monitoring of the drug’s safety in the wider population occurs, and any new side effects or issues are reported to regulatory agencies.

Throughout the process, many drug candidates fail to make it to the next stage, often due to efficacy, safety concerns, or financial constraints. As a result, the entire process from discovery to market can take 10-15 years or longer, with a low success rate, which is why the cost of developing a new drug is so high.