PCL WEEK 1

Lecture 1: (week 1)

  • What are we choosing to call unmet medical need?

  • In 2024 50 drugs were approved by FDA

  • Drug development is an expensive process 

  • How diseases are basically particular protein where we aim our drugs to fight



Lecture 2: (week 1) 

Unmet Medical Needs:

  • 3.4 billion prescription/ year in the US

  • 75% of visiting doctors involve prescribing medicine

  • Since 2000, 900 new drugs have been put over 8000 drugs are in development

  • First in class drug, or pioneer drugs which target protein that hasn't been targeted before 

DRUG DEVELOPMENT PIPELINE (the process)

  • Preclinic: laboratory work to asses how safe the material is and does it work? May start with 5000 chemicals and test out what works and what doesn't 

  • If it does then it goes to whether it can be used on human (submit request to FDA) 

  • Phase 1= healthy volunteers to see if medication works on people who arent at risk 

  • Only 5 chemicals made it past 

  • Use more people 

  • Ask FDA again and whether it can be approved and give license to company to sell 

  • More often than not its not approved and needs more evidence 



  • The pipeline reduces risk of exposing people to drugs that have unknown safety therefore small clinical trials with small amounts of people and then gradually increase 



WHAT KIND OF DRUGS ARE BEING APPROVED

  • The most popular is oncology meds- cancer meds

  • Second is infectious disease from 2015-2019 and neurology from 2020



  • What should we work on though? Where should we make drugs? 

  • Should we develop areas that already have drugs or develop areas where there arent?

  • WHO list of essential medications every country should have in their toolbox for emergency 

  • Take into account: how common and deadly the disease is, efficacy and cost effective, safety of drug 

  • Disability-adjusted life years- 1 DALY means 1 lost year of healthy life (measures how much it impacts people) 



UNMET MEDICAL NEEDS:

  • Who decides it is unmet?

  • A regulatory agency looks at global evaluation

  • They study DALY to see what to worry about more? Eg cancer, heart disease etc

  • Patient advocacy groups also influence



Immense attrition (drop out) during drug development:

  • Number of chemical compounds you start off with vs end

  • Start with a lot and only 5 enter trials and 1 getting approved 



  1. Step in pipeline

  • Considerations: is the condition life threatening?, are patients satisfied with curren thterapy, how could a new med be better like efficacy wise? Or safety and few side effects, convenience take once a day



  1. Drug discovery phase

  • Choose a disease

  • Identification and validation of drug target

  • DRUG TARGET: a molecule usually a protein involved in the disease that the drug binds to to inactivate the molecule

  • Figure out what chemical actually works 



  • Disease mechanism and model 

  • Target protein shape- can the drug actually interact with the protein with its shape

  • For the FDA safety has to be at least in two animals than human beings



  1. Clinical trials

  • Recruiting volunteers (they all have to be approved by the ethics board)

Phase 1

  • Purpose: determine dosage and pharmacokinetics so how the drug moves in body

  • Design: slowly increase dose

  • Subjects: usually healthy vilunteers, sometimes with disease, patient can drop out whenever 

Phase 2

  • To check efficacy

  • Subjects: Patients with disease

  • Design: compare treated individuals to control individuals and whether it can make it better and have a result (eg compare to other drugs in the market, or placebos which are pills with no drug to check the placebo effect)

PLACEBO EFFECT

  • Body response to taking what you think is a drug

  • Actually, brain circuits involved 

  • Phase 2 uses blinding trials to reduce bias

  • Single-blind: subjects don't know who is getting treatment and the placebo

  • Double-blind: neither the subject nor the investigator know (but it in computer recorded so you will know)



Phase 3

  • Patient with disease

  • What is the difference between phase 2 and 3? 



People don’t participate in clinical trials therefore not a lot of drugs are being developed



Drug development is a business

  • Patent protection gives company 20 years to make the drug and get it approved and after anyone can do it

  • The cost of getting a single drug to the market:

  • Over 2 billion dollars including cost of failure and 15 years



Dr Ian’s Video: 

  • Gorlins syndrome:

  • High risk of getting skin cancer and tumour

  • Constant growht of basal cell carcinomas 



  • Started in 1950 where lambs were born with one eye in their forehead

  • Cause was that pregnant lambs were eating something that interfered the normal pathway

  • This was due to cow cabbage which inhibits the SHH pathway and blocked development pathway


  • Constant growht of basal cell carcinomas was due to sonic hedgehog pathway

  • This pathway is important because it effects the division of two lobes

  • If the pathway stays on (overactivation) then it cause cancer

  • However the compound (cyclopamine) in cow cabbage can switch it off?

  • Cyclopamine can switch off sonic pathway

A woman with gorlins syndrome was gonna be in the clinical trial however she wanted to know what benefits she would get but she wasnt getting any so development stopped. However wasn't her or the scientists fault cause scientists have a lot of people investing and has to pay back and she wants benefit after being used too



  • Together, these examples underscore the SHH gene's critical role in embryonic development and how its disruption leads to profound effects across species



Reading: WHO Essential Medicines:

  • Essential Medicine is for the population and should be available affordable and of good quality

  • They are always available in sufficient amounts and doses to ensure they address the population's needs

  • It covers a wide range of health needs but only represents a small portion ofthe  total number of medicines

  • Over 150 countries have an essential medicine list based on WHO’s

  • The idea is to have limited number of carefully selected medicines

  • Also controls better costs

  • The government makes the essential medicine list to address that nation's primary health needs depending on what disease is happening, resource availability etc

  • WHO’s model list is a blueprint to help the countries develop their list