Ensuring Fast Patient Enrollmentby Placing Clinical Trials in Russia

and Ukraine

Partnerships in Clinical Trials Russia-CIS2013

OCT: CRO in Russia,Central and Eastern Europe

Clinical Trials Industry in Russia and Ukraine

• The first international trial conducted in early 1990-s• Russia: 916 new clinical trials in 2012 - 60% increase

over 2011• 534 studies are ongoing in Russia• 219 studies ongoing in Ukraine• Clinical market in CIS to exceed €700m in 2014

What is expected by global partners?

Overall Indexed Clinical Trial Costs

Clinical Trial Costs in Russia and Ukraine

• Shorter enrollment period• Lower PI grant expectations• Lower vendor costs• Hourly rates of clinical research specialists inthe region are twice lower than in the USA

Investigator fees vary per region

Western Europe CIS Latin America Asia The USA0

1000

2000

3000

4000

5000

6000

7000

Average per patient investigator fee ($)

FDA Inspections Since 2005Region Countries #Inspections NAI VAI OAI

CIS Russia, Ukraine, Georgia 82 69,5% 29,3% 1,2%

Europe All EU States 274 54,0% 45,6% 0,4%

The US United States 1759 48,7% 44,1% 7,2%

India India 33 54,5% 45,5% 0%

China China 13 38,5% 61,5% 0%

Middle East Israel, Turkey 26 34,6% 57,7% 7,7%

High Quality Data in CIS Region

• GCP accepted as a National Standard• MDs must complete 6 years of med. school + 1-3

years of residency• MDs are re-certified each 5 years. • PI must be certified in the therapeutic area• Requirement of >5 years of experience for PI in

clinical trials• Highly qualified staff in CROs

Quick Enrollment• Large patient population:

Russia – 143 MUkraine – 49 M

• 70% of population located in large cities• Centralized healthcare system• Increasing clinical infrastructure growth• Investigators eager• Established patients’ databases• Patients see trials as opportunity• Large % of drug naïve patients• Fewer competing trials

Number of Clinical Trials Russia

Ukraine

75% of studies approved in 2012 in Russia are conducted in 8 therapeutic areas:

On-cology(110)

Pul-monolog

y(65)

Endocrinology(61)

Muscu-loskeletal dis-eases

(45)

Infec-tious

diseases(45)

Cardi-ology(42)

GE (35)

Psychiatry(32)

Ensuring Fast Enrollment Through Feasibility

• Is the disease under study relevant to the patient population?

• Is the study design, comparators, and subjects’ visits acceptable?

• What are the anticipated Regulatory and Ethical challenges?

• What are the general timelines for study approval and site start-up?

IS THE DISEASE UNDER STUDY RELEVANT TO THE PATIENT

POPULATION?

Global rates of cardiovascular disease

Global rates of Rheumatoid Arthritis

Incidence of Stomach Cancer in Males

IS THE STUDY DESIGN, COMPARATORS ACCEPTABLE?

Acceptance of Protocol design

• Is comparator drug registeredin Russia and Ukraine?

• Is comparator drug used in Russiaand Ukraine as SOC?

• Is specific equipment availableat sites?

WHAT ARE THE ANTICIPATED REGULATORY AND ETHICAL

CHALLENGES?

Phase I studies in Russia

• Phase I in healthy volunteers studies of medications produced outside of Russia are forbidden in accordance with FZ-61

• “1) to establish safety and/or tolerance of medicinal products for healthy volunteers, except for the trials of medicinal products manufactured outside the Russian Federation;”

Pre-clinical Studies for Generics

• Comparative acute toxicity in rodents• Comparative sub-acute toxicity in

rats/rabbits/dogs

No Scientific AdviseWays to get opinion from Regulators

Unofficial expert advice

• No guarantees

• Not legal

• Quick

Official comments after CTA decline

• Official and legal

• Time consuming

No official guidelines

• No definition for biosimilar drugs

• No official documents describing regulatory requirements for the quality, pre-clinical and clinical studies for biosimilars

But:

Biosimilar and biobetter drugs are under development in Russia

WHAT ARE THE GENERAL TIMELINES FOR STUDY APPROVAL

AND SITE START-UP?

Average time from application submission to final study approval (days)

Regulatory approval timelines

Estonia

Lithuania

Latvia

Bulgaria

Belarus

Ukraine

Russia

30 60 90 1200

Case Study. Ovarian Cancer

• FDA and EMA-controlled study• Multinational phase III study of a

chemotherapy agent in women with ovarian cancer

• 600 patients enrolled in Russia, Ukraine, Belarus, Latvia, Lithuania and Bulgaria within a 3,5 year timeline

• Due to the law recruitment rates in Western Europe, Russia was requested to enroll extra 60 Pts.

• Total: 658 patients at 70 sites

Case Study. Ovarian Cancer

0

100

200

300

400

500

600

700Enrolment within 3,5 years

6 CEE Countries 8 Western-EU Countries

Questions