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Question 7 of 20 Fundamentals Concept

What are the main stages from target to approved drug, and how many programs survive?

Short answer

A program runs through target identification and validation, hit finding, lead optimization, preclinical safety, then phase 1, 2 and 3 trials and regulatory review. Across all indications, about 14 percent of programs that reach phase 1 eventually win approval, and most of the loss happens in phase 2.

Why

Each stage asks a different question. Target work asks whether changing this protein should change the disease. Hit finding asks whether any molecule binds it.

Lead optimization balances potency, selectivity, solubility, metabolism and safety at once. Preclinical work asks whether a dose that works is tolerated. Phase 1 looks mainly at safety and pharmacokinetics in a small group, phase 2 at whether the drug does anything in patients, and phase 3 at whether that holds in a large controlled trial.

Wong, Siah and Lo analysed about 406,000 trial data points from 2000 to 2015 and estimated the overall probability of success from phase 1 to approval at 13.8 percent, higher than some earlier estimates of about 10 percent. Their phase-by-phase numbers show the shape of the problem, with phase 2 to phase 3 transition around 58 percent and phase 3 to approval around 59 percent in their data. Rates differ a lot by therapeutic area and by whether a biomarker guides patient selection.

These figures are conditional on entering clinical trials. Counting from the start of discovery, the fraction is far smaller, which is why early decisions about target quality matter more than speed.

A strong answer covers

  • Target validation, hit finding, lead optimization, preclinical, three clinical phases
  • About 13.8 percent of phase 1 programs reach approval
  • Phase 2 is where most programs fail
  • Success rates vary by therapeutic area and biomarker use
  • Figures are conditional on reaching the clinic

Common mistakes

  • Quoting a single success rate as if it applied to every disease area
  • Treating preclinical activity as the main hurdle rather than clinical efficacy
  • Confusing probability of approval from phase 1 with probability from discovery