Challenges with orphan drug trials

Question 1

Epidemiology of rare diseases?

Answer 1

• Europe affects <5 in 10,000

* America < 200,000

Question 2

What is an orphan drug?

Answer 2

• Drug developed to treat rare or neglected disease
• Requires regulatory approval

Based on:
• Needs to be serious, chronic or life-threatening
• No authorised treatment available

Question 3

Statistics

Answer 3

• More than 7000 diseases
• More than 250 new types every year
• Can take 8 years to be diagnosed
• 80% linked to gene mutations
• 350 million people worldwide affected
• Only 400 rare diseases have approved treatments

Question 4

Standard drug approval

Answer 4

Drug discovery  manufacture  clinical trials  marketing application (application needs to show effectiveness, good quality and strength of drug and benefits outweighs risk)

Clinical trials in rare diseases
• Small population
• Drug supply chain can be difficult
• Limited comprehensive data

Question 5

2 documents supporting drug approval pathway

Answer 5

Study protocol
•	Reason for study
•	Study design
•	Eligibility & number of participants
•	Schedule of dosing
•	Data collection

IMPD – investigational medicinal product dossier – supply chain
• Raw material
• Manufacturer
• Distribution logistics
• Clinical site
• Information of chemistry, manufacturing process, tests carried to show quality of drug

Question 6

Clinical trials in rare diseases

Answer 6

• No randomisation as unfair for people to take placebo
• Not double blind
• Unlikely to find patients with same disease

Question 7

Endpoint

Answer 7

• Measure to assess whether people feel/function better

* If they live longer with treatment

Question 8

Surrogate endpoints

Answer 8

• Substitute for measuring how patients feels, function or survives
• Predicts clinical benefit of drug
• Lab results, imaging results, psychological measures

Question 9

Challenges to design study for rare disease

Answer 9

Small patient population
• Not many have disease
• Sample size due to patient numbers, rather than stats
• Patients all over the world

Poor disease understanding
• No natural history studies – so we don’t know how symptoms last, progress over time
• Heterogenous diseases phenotype and disease course
• Lack of prior clinical studies
• Difficulty in selecting clinical endpoints
• Unknown study duration

Clinical challenges
• Disease experts live all around the world
• High patient drop-out
• Patient fragility