1. Status of the Biosimilar Market
Approvals, Challenges, and Outlook
Jason J Braithwaite, PharmD, MS, BCPS
Senior Director, Clinical Pharmacy Services - HealthTrust
2. Disclosures
• The presenter has no conflicts of interest to disclose
• This presentation is based on nationally published information and
health-systems experience and is not intended to promote any
particular drug or manufacturer
3. Objectives
• Examine key characteristics of biosimilars that create different market
dynamics in the US
• Outline current and historical roadblocks to biosimilar approval and
adoption
• Identify the lost value between the FDA approval and market launch
of biosimilars agents in the US
4. Biosimilar Introduction
The US has three
definitions for biologic
medicines – Biologic
(reference), Biosimilar,
Interchangeable Biologic;
Most regulatory bodies
only have two definitions –
Biologic or Biosimilar
5. The 80 – 20 Rule
40
60
TOTAL US PHARMACEUTICAL SPEND
Biologics Drugs
…but 40% of spend is on biologics
2% of people use biologics
40 – 2
X
X
8. Bio5imi1ars by 7he Number5
17
58
7
631
0
0
Biosimilars FDA approved through Jan 2019
Biosimilars approved in Europe
Biosimilars launched in the US through Jan 2019
Average days from FDA approval to market launch
US biosimilars with “Interchangeability” status
European biosimilars that require interchangeability status to allow
automatic interchange
10. Biologic and Biosimilar Pipeline
Biosimilar Pipeline Biobetter Pipeline
0
5
10
15
20
25
30
35
Biosimilar Pipeline
Biosimilar Pipeline
0
1
2
3
4
5
6
7
Developing Phase 1 Phase 2 Phase 3 Pending Withdrawn
Biobetter Pipeline
Biobetter Pipeline
A biobetter can be thought of as an improved version of an existing biological product. For example, a
biobetter may have a change in structure that makes it safer or more effective, or a change in formulation
that makes it easier to administer or allows fewer courses of treatment. Biobetters are different from the
existing product and evaluated as new drugs. Biobetters are not covered under the BPCIA.
11. Biosimilar Switching
Switching Safety
Efficacy
Quality
To date, no new safety or efficacy concerns have been detected in the over 10 years and greater
than 700 million days of patient experience with biosimilars.
Comment from Biosimilars Medicines Group, A Medicines for Europe sector group. Docket submission and presentation to the Oncologic Drugs
Advisory Committee meeting of 13 July 2017. https://www.regulations.gov/document?D=FDA-2017-N-2732-0006. Accesed 21 Nov 2017.
Real World Evidence
12. 2019 US Biosimilar Expectations
Biosimilar
Brand
Biologic
# w/ FDA
Approval
Number of
Possible Launches
Number of Potential
Biosimilars in 2019
US Spend
Bevacizumab Avastin 1 2 2 $2.9B
Trastuzumab Herceptin 3 5 5 $1.5B
Rituximab Rituxan 1 1 1 $4.1B
Pegfilgrastim Neulasta 2 1* 2 $4.2B
Filgrastim Neupogen 3** 2 5** $0.8B
Etanercept Enbrel 1 1 1 $7.4B
* Already launched in 2019
** Includes Granix
Information based on several public resources – Not all manufacturer data is available to the public, therefore data
may not be comprehensive
Year of the Oncology Biosimilar
• $13.5B in oncology spend will face new/additional biosimilar competition in 2019
Oncology
Biosimilars
13. Audience Polling Question #1
Which of the following choices are considered roadblocks to biosimilar
adoption in the US?
a. Rebate traps and payor alignment
b. Reimbursement models
c. Pay to delay tactics
d. Interchangeability requirements
e. Provider and Patient education on biosimilars
f. None of the above
g. All of the above
14. Audience Polling Question #1
Which of the following choices are considered roadblocks to biosimilar
adoption in the US?
a. Rebate traps and payor alignment
b. Reimbursement models
c. Pay to delay tactics
d. Interchangeability requirements
e. Provider and Patient education on biosimilars
f. None of the above
g. All of the above
16. Characteristic Rapid Delayed
1. Indications -Most or all indications on label -Key missing labeled indications
2. Chronic vs Episodic Treatment -Episodic (i.e. short-term) -Chronic
3. Payor Preference -Prefer biosimilars
-Parity w/ other biosimilars
-Brand preferred
-Choosing a preferred biosimilar (2 or more avail)
4. Objective vs Subjective Measure -Objective (i.e. WBC, HGB) -Subjective (i.e. symptoms resolved)
5. Need for Interchangeability -Low need (i.e. physician, hospital) -Required (i.e. retail, referral infusion)
17. Market Success of One Biosimilar…..
Biosimilar Characteristic of Biosimilar Expected Impact to Adoption
Etanercept - Chronic treatment
- Roughly 50% of indications on label
- Payor (unknown)
- Subjective outcome measure
- Significant interchangeability impact
- Delayed
- Delayed
- Unclear
- Delayed
- Delayed
Filgrastim - Episodic treatment
- Vast majority of indications on label
- Payor parity or preference
- Objective outcome measure
- Minimal/no interchangeability impact
- Rapid
- Rapid
- Rapid
- Rapid
- Rapid
Is not a predictor of the success of other biosimilars
18. Perspectives:
Infliximab Issue Impact
Chronic Treatment Patient concern when well controlled on current therapy
Branded Manufacturer Contracts Tie Pharma
and Non-pharma (VOO, Pro-IMD, Pro-IOMD)
Delays adoption as non-pharma products will lose rebate and negate
savings
Rebate Trap Branded manufacturer contracted directly with payors to achieve
“preferred” status
Patient/Physician Education on Switching Minimal access to European data and physicians uncertain about data,
revenue, reimbursement provide little incentive to switch
Revenue impact Controllers, office managers may have preference for higher revenue
Don’t let one biosimilar shape the way you view the adoption of all biosimilars in the US
20. Roadblocks to Biosimilar Market Adoption
Resolved
• Separate J-codes
• Part D coverage gap discount
• Pass-through status remains…
for now
Current
• Reimbursement models
• Payor preference / Rebate trap
• Provider and Patient education
• Interchangeability
• Discount pricing
21. Roadblocks – Reimbursement Models
• Providers are reimbursed for innovator biologics, with an additional
percentage to cover acquisition, storage, and dispensing costs
• Medicare: ASP + 6%
• Commercial: ASP + 9-10%
• Medicare has adapted to provide ASP + 6% of reference biologic to
incentivize use of biosimilars
• Commercial has NOT followed (only 3% have adopted this model)
• Commercial reimbursement majority of provider billing
Fixed % of ASP is a financial disincentive
for providers to favor a biosimilar
https://www.fiercehealthcare.com/hospitals/hospital-impact-reimbursement-models-a-roadblock-to-biosimilar-adoption
22. Roadblocks – Reimbursement Models
Pass Through Status Example
• Biosimilar is allowed this status for 2-3
years from approval – after 2-3 years
the biosimilar agent is no longer
advantaged for 340B entities
• During pass-through: ASP + 6% of
reference biologic
• After pass-through: ASP – 22.5%
Commercial Incentives Example
• Biologic $1,000/dose and biosimilar
w/ 15% discount leads to biosimilar
gross profit loss of
• 340B Hospital: $78 per dose
• Outpatient Hospital: $42 per dose
• Physician Office: $8 per dose
Two significant roadblocks remain
Adds up to tens of thousands in gross profit loss for busy practice with chronic
recurring treatments
1. After 2-3 yrs are providers
incentivized to go back to biologic?
2. Do providers jump from one
biosimilar to the next to chase this
reimbursement?
https://www.fiercehealthcare.com/hospitals/hospital-impact-reimbursement-models-a-roadblock-to-biosimilar-adoption
23. Roadblocks - Reimbursement Models
Pre – ASP Established Reimbursement
• Historically Medicare would
reimburse WAC + 6% prior to
established ASP (2 quarters)
• NEW for 2019 – Medicare is
reducing reimbursement to WAC
+ 3% during ASP establishment
period
ASP Model Creates Winners and Losers
https://www.biosimilardevelopment.com/doc/why-so-slow-demystifying-the-barriers-to-u-s-biosimilar-adoption-0001
24. Roadblocks – Rebate Traps
• Managed care programs have stated that discounts of >25% are
necessary to overcome the rebate trap and adopt competitor
• Why are savings going to the entity with the least risk, accountability, and
ability to change prescribing patterns?
• Employers (and their plans) are focused on rebate amounts –
Providers are focused on acquisition cost
• Low hanging fruit – when employee benefits and provider are same company
• Rebate traps are now leaking into the biosimilar competitors who
are competing for position
• Biosimilar manufacturers are paying rebates to put their biosimilar ahead of
other biosimilars
Call them early and often to tell
them your formulary decision
https://biosimilarsrr.com/2018/01/09/escape-rebate-trap/
25. Learning From the Generics
• The Drug Price Competition and Patent Term
Restoration Act (Hatch-Waxman Act) of 1984
established the generic drug market of today
• THEN: 1983, 35% of the top-selling brand drugs
had expired patents and generic competition
• 13% generic adoption
• NOW: 2017, 9/10 of ALL prescriptions are filled
with generic drugs
• 97% generic adoption
https://accessiblemeds.org/resources/blog/2018-generic-drug-access-and-savings-report
26. Learning From the Generics
Limiting Factors of Generic Adoption
• Brand loyalty
• Pre-entry market size
• Drug characteristics
• Regulation that promotes generic
substitution and reduces market
barriers
• Brand company strategy to
minimize impact of generic
adoption
Berndt, E R, and M L Aitken (2010), “Brand loyalty, generic entry and price competition in pharmaceuticals in the quarter century after the
1984 Waxman–Hatch Legislation”, NBER Working Paper 16431
27. Audience Polling Question #2
Which of the following choices most closely represents the time
between FDA approval of a biosimilar and the US market launch of the
biosimilar?
a. < 30 days
b. 90 days
c. 180 days
d. 365 days
e. 630 days
28. Audience Polling Question #2
Which of the following choices most closely represents the time
between FDA approval of a biosimilar and the US market launch of the
biosimilar?
a. < 30 days
b. 90 days
c. 180 days
d. 365 days
e. 630 days
29. Failure to Launch
To launch in the
market, sometimes
biosimilars just need
a little push
Featuring: every
biosimilar company
to date
Supporting cast: health-
systems, providers, payors
In a market where 17 are approved, only 7 are available, and no biosimilar agents are the
majority of the market share…. We have a failure to launch situation
30. Failure to Launch
• Patent thicket and patent dance
• Pay to delay
• Manufacturing issues and supply
• FDA CRLs for data
• Many manufacturers began trials prior to final FDA guidance
31. Biosimilar FDA
Approval Date VS
Market Launch:
Evaluating the impact of
delayed market availability
Originator
Biologic
Biosimilar Date of First CRL Date of FDA Approval
Launch Date
Earliest possible launch
Days between
approval and launch
Neupogen Zarxio -- March 6, 2015 September 3, 2015 181
Remicade Inflectra June 8, 2015 April 5, 2016 November 28, 2016 237
Enbrel Erelzi -- August 30, 2016 July 1, 2019 1,035
Humira Amjevita -- September 23, 2016 January 31, 2023** 2,321
Remicade Renflexis -- April 21, 2017 Jul 24, 2017 94
Humira Cyltezo -- August 25, 2017 January 31, 2023** 1,985
Avastin Mvasi -- September 14, 2017 July 1, 2019 655
Herceptin Ogivri -- December 1, 2017 July 1, 2019 577
Remicade Ixifiˆ December 12, 2017 N/A N/A
Procrit Retacrit October 16, 2015 May 15, 2018 November 12, 2018 181
Neulasta Fulphila October 6, 2017 June 4, 2018 July 9, 2018 35*
Neupogen Nivestym -- July 20, 2018 October 3, 2018 75
Rituxan Truxima April 5, 2018 November 28, 2018 June 15, 2019 199
Humira Hyrimoz -- October 30, 2018 January 31, 2023** 1,554
Neulasta Udenyca June 9, 2017 November 2, 2018 January 3, 2019 62
Herceptin Herzuma December 14, 2018 June 1, 2019 169
Herceptin Ontruzant January 18, 2019 June 1, 2019 134
631 days or 1.73 yrs
CRL= Complete Response Letter
32. 2015 2016 2017 2018 2019 2020 2021 2022 2023
Zarxio
237
Inflectra
1,035 days
days
Erelzi
Amjevita
1,035
2,321
94
Renflexis
Cyltezo
1,985
Mvasi
655
Ogivri
577
Retacrit
Fulphila
75
Nivestym
181
181
Truxima
199
Hyrimoz
1,554
62
Udenyca
942
237
511
303
35
241
Time between 1st CRL and Approval
Time between Approval and Expected Launch
Time between Approval and Actual Launch
Legend
Approved Biosimilar Timeline: The Long and Winding Road
Days
Years
447 day delay in
pre-FDA approval
due to CRL
138 day delay from
FDA approval to
Actual Launch
959 day delay from
FDA approval to
Expected Launch
Launched
Awaiting
Launch
33. • Provider uneasiness of delay (unaware of the reason for delay)
• Timing of health-system adoption
• Manufacturer uneasiness regarding the market adoption and return
on investment
• Economic impact to systems and providers
• Delays in product approval and launch have estimated cost of $49.5B to US
healthcare
Impact of Delayed Launches
35. Why is Europe Successful?
Reason #1 – Head Start
• Five year head start on regulatory framework
• Nine year head start on first approval
• By the time the US had launched its first official biosimilar (Zarxio), Europe had 21
approved biosimilars on the market
Reason #2 – Minimal payor disruption
• No preference for reference biologic, rebate traps, and variations at local/regional level
Reason #3 – Ensure safety and efficacy but leave policy to individual states
• EU doesn’t regulate interchangeability or switching – leaving it up to individual states to
regulate
39. Overcoming the Roadblocks
1. Speed up the approval and launch – FDA action plan, patent thicket
changes, US paying while EU playing, non-US real-world evidence
2. Reimbursement models – ASP model needs to change to better
incent the uptake of biosimilar agents without loss of revenue
a. Fixed reimbursement model?
3. Rebate traps – uncoupling of the biosimilar from the biologic
market basket would allow both to remain available but not
compete against each other for preference status
a. Use employer arm to promote biosimilar adoption
40. Overcoming the Roadblocks
4. Provider and Patient Education - Improve the synthesis and
dissemination of real-world data from the US and Europe, allow use
of European studies to gain FDA approval
5. Interchangeability – much more can be done at the State-level to
impact the interchangeability of products
a. collaborative practice agreements exist that allow outpatient pharmacists to
engage in therapeutic substitution
b. Hospital P&T policy should promote class interchangeability vs approving a
certain product or manufacturer
43. FDA’s Biosimilar Action Plan
1. Standardize review template to improve efficiency of the FDA review and approval
2. Build models and simulations to correlate PK/PD responses with clinical response
3. Enhance the purple book on approved biosimilars
4. Explore potential for data sharing agreements with foreign regulators to increase the use of non-US-licensed
products to support a biosimilar application
5. Establish new Office of Therapeutic Biologics and Biosimilars (OTBB) to coordinate and support the activities
under the Biosimilar User Fee Act (BsUFA) to improve efficiency and enhance policy development
6. Enhance the provider education via the production and release of videos that explain key concepts of
biosimilars and interchangeable products
7. Publish the final or revised draft guidance on biosimilar product labeling to clarify requirements for sponsors
44. FDA’s Biosimilar Action Plan
8. Provide clarity for product developers on demonstrating interchangeability by publishing guidance
9. Provide additional clarity and FLEXIBILITY on data analytic approaches and statistical methods
10. Provide additional support to product developers regarding quality and manufacturing processes by
delineating the most critical attributes to evaluate and explore ways to reduce the number of lots required for
testing
11. Engage the public on what additional policy steps the FDA should consider to improve the program
46. Overcoming the Switching Obstacle
Many argue that there isn’t enough data to support
switching, especially multiple switches on the same
patient.
• Given that biologics are made through living
organisms or through complicated manufacturing
processes – patients have already been exposed to de
facto multiple switches for many originator biologics
when product quality attributes changed after one or
more manufacturing process modifications were
introduced.
• In short, manufacturing variations from batch to
batch of a biologic are similar to variations you can
expect from moving from a biologic to a biosimilar.
