Overview of the - Healthcare ecosystem complexity increasing rapidly - Pharma industry is facing a crisis: trends shaping the industry - RWE complements RCTs and captures implementation of innovation - RWE is one component of the integrated evidence needed for stakeholders - Integrated Evidence: Optimizing patient access - Integrated Evidence: Label expansion - Maximizing the value of data requires a scalable platform and expertise

1. What’s next in RWE?
Amy Rudolph, Head Evidence and Launch Excellence
Global Medical Affairs
Novartis Pharmaceuticals Corporation

2. Disclaimer
The views and opinions expressed in this presentation are those of the author
and do not necessarily reflect the official policy or position of Novartis.
2

3. Healthcare ecosystem complexity increasing rapidly
 Holistic understanding of care
in healthcare ecosystem
 Evidence across entire data
continuum throughout lifecycle
FUTURE
Formulary/
Drug list
MEDICAL
COMMUNITY
REIMBURSEMENT
SYSTEM
TECHNOLOGY
ENVIRONMENT
Group practice,
HCP Network
Pay for
performance
Value based
contracts
Electronic
medical records
Health
monitoring
Prescription
services
Medical
Experts
Medical
Associations
Academics
REGULATORY
Patients
3
 Top expert engagement with focus on RCTs
and regulatory approval
 Target population with limited generalizability
 Narrow scope of medical activities
REGULATORY
Medical
Experts
Medical
Associations
Academics
Patients
PHYSICIANS
HISTORIC

4. R&D returns over the last decade from 10.1% in 2010
to 1.8% in 2019
Return on late-stage portfolio2
0
50
100
150
200
250
0%
2%
4%
6%
8%
10%
12%
2010 2011 2012 2013 2014 2015 2016 2017 2018
Assets
in
development
Absolute
IRR
Industry average
Pharma industry is facing a crisis:
trends shaping the industry
4
$3.2 billion
Average cost of R&D
required to bring a
new drug to market2
>12 years
Drug time to
market3
9.6 %
Likelihood of
approvals from
Phase I clinical trials3
 High cost of development (1X*)
 Long timelines of drug R&D (10X*)
 High failure rates (24X)
Struggle in further developing breakthrough therapies
 Empirical, sequential, physical slow drug R&D process
creates friction for therapies to reach patients
Struggle in further developing breakthrough therapies
Willingness to pay for expensive therapies is going down;
complex regulatory landscape
 We observe change in business model where customers
are shifting from providers to payers & healthcare systems
Multiplier effect on Drug ROI
IRR, incidence rate ratio; ROI, return on investment.
1. Wouters OJ et al. JAMA 2020;323:844-853; 2. Takeba T et al. Clin Transl Sci 2018;11:597-606

5. RWE complements RCTs and captures
implementation of innovation
RWE provides insights into disease behaviour and effectiveness for broader populations in healthcare systems
PAST NOW
IMPORTANCE
RCT Data
Non
RCT Data
5
RCT, randomized controlled trial; RWE, real-world evidence.

6. RWE is one component of the integrated
evidence needed for stakeholders
Integrated Evidence
 Holistic evidence for stakeholders (HCPs, regulators,
HTAs, patients etc.) to transform medical practice,
maximize access and clinical adoption
RCT
 Interventional studies conducted in a controlled
setting in a pre-defined patient population
RWE
 Evidence generated from healthcare data collected
under routine clinical practice circumstances*
Digital, labs,
imaging,
genomic, RCT
with RWD arm
Claims, EHR,
registries, safety
case reports,...
Clinical
trials
RWE
Routine Clinical Practice
RCT
Controlled Setting
Data
Sources
Patients Providers Payers
INTEGRATED EVIDENCE
Patients Regulators
Policy/HTA/
Payers
Providers/
HCPs
6
*Includes evidence on diseases, their impact on patients and healthcare systems as well as on the
usage and potential benefits or risks of medicinal products and/or interventions.
EHR, electronic health records; HCP, healthcare professional; HTA, health technology assessment;
RCT, randomized controlled trial; RWD, real-world data; RWE, real-world evidence.
IE planning starts early

7. Integrated Evidence: Optimizing patient access
RWE can provide evidence of clinical benefit of new therapies in ultra-rare
or difficult-to-treat populations
• Retrospective chart review of 57 PROS patients
across 6 countries and 9 sites to evaluate the safety and
effectiveness of Piqray (prescribed via MAP)
• Total evidence package included clinical data, images,
photographs, videos, individual patient transcripts...
SOLUTION
2
• PROS encompasses rare/life-threatening diverse
genetic syndromes with high unmet need
• Single-institution study of 19 PROS patients showed
rapid and significant efficacy of Piqray without
additional safety concerns
SITUATION
1
7 FDA, US Food and Drug Administration; MA, marketing authorization; MAA, marketing authorization
application; MAP, managed access program; PROS, PIK3CA-related overgrowth spectrum.
• Results to support FDA approval for treatment of
PROS with Piqray
• Integrated Evidence approach enabled US approval and
broad access to treatment for PROS patients 2 years
earlier than planned
IMPACT
3
Safety and
effectiveness
FDA MAA
Patient
charts

8. Integrated Evidence: Label expansion
The rare disease AOSD was approved by the FDA as an indication for canakinumab in
June 2020, based on the integrated evidence presented in the submission package
8
To support the label extension for Ilaris, RCT data were supplemented with:
• To demonstrate efficacy
independent of pediatric age group
POOLED SJIA DATA FROM
NOVARTIS IN-HOUSE STUDIES
• To demonstrate positive numeric
trends with Ilaris vs placebo
THE RESULTS OF
A TERMINATED IIT
• To demonstrate similar exposure
responses for AOSD and SJIA
A PK ANALYSIS
• To demonstrate similar outcomes
for AOSD and SJIA
A BAYESIAN ANALYSIS
• For AOSD and SJIA
SIMILAR SAFETY DATA
• To demonstrate evidence of disease
continuum of AOSD and SJIA and
efficacy of other IL-1 inhibitors
A LITERATURE REVIEW
AOSD, adult-onset Still’s disease; IIT, Investigator-initiated trial; PK, pharmacokinetics; RCT, randomized
controlled trial; SJIA, Systemic Juvenile Idiopathic Arthritis.
Information provided by speaker

9. Maximizing the value of data requires a
scalable platform and expertise
9
Scientific & medical expertise
Our access to scientific and medical
experts enables the design, testing
and development of applications
based on stakeholder needs
Development of an industry-defining platform to transform the R&D process
and improve patients’ lives
Label expansion through drug
repurposing (higher revenue)
Focused patient cohorts
(higher likelihood of success)
Virtual trials: Virtual control arms and
improved trial design (lower trial cost)
Benefits
Our data represents one of the
largest datasets in the industry

10. We are evolving for patients
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11. Thank you