Transcript Click here for the PowerPoint presentation: Biosimlars-GPHA

Biosimilars:
What to Expect
Joshua A. Meeks
Pharm D.
Encompass Rx
[email protected]
EncompassRx – 404-367-9111
Disclosures
 Joshua A. Meeks, Pharm D, is employed by
Encompass Rx specialty pharmacy and
declares no conflicts of interest, real or
apparent, and no financial interests in any
company, product, or service mentioned in
this activity, including grants, employment,
gifts, or stock holdings.
Learning Objectives
1. Review recently approved specialty medications and
recognize emerging specialty therapies
2. Evaluate the impact of new and emerging specialty
medications on patients and payers
3. Develop strategies to manage costs and facilitate
appropriate access to specialty medications
4. Recognize the role of specialty pharmacies and pharmacists
in educating patients and managing specialty medications
5. Define biosimilars and recognize the role of biosimilars in
the specialty market
6. Assess potential issues and barriers associated with
biosimilars
Spending on biologic medicines grew by 9.6% to 28% of the total
spending in 2013, up from 21% in 2008, with most of the growth
due to significant innovations in cancer and autoimmune diseases.
http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Corporate/IMS%20Health%20Institute/Reports/US_Use_of_Meds_2013/2
013_Medicine_Spending.pdf
Today’s Market
1
2
3
4
5
6
7
8
9
10
Top Selling Drugs by Sales (2015)
Humira
Harvoni
Enbrel
Remicade
Rituxan
Lantus
Avastin
Herceptin
Revlimid
Sovaldi
Sales in Millions
14,012
13,864
8,697
8,355
7,115
7,029
6,751
6,603
5,801
5,276
http://www.pharmacompass.com/pharma-news/top-drugs-by-sales-revenue-in-2015-who-sold-the-biggest-blockbuster-drugs
 Biologics make up 29%
of total global
pharmaceutical sales
Specialty and biologics
drugs to make up
majority of pipeline
http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Corporate/IMS%20Health%20Institute/Reports/US_Use_of_Meds_2013/2013_Medicine_Spending.pdf
What is a biologic?
 A macro molecule derived from natural
components
 Extremely sensitive to environmental
changes which may alter their chemical
structure and functionality
 Batch to batch variation in products
1MORROW
T, Felcone LH. Defining the difference: What Makes Biologics Unique. Biotechnology Healthcare. 2004;1(4):24-29.
and Drug Administration. Biosimilars.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Bio
similars/ (Accessed 2015 November 7)
2Food
Complex Manufacturing
 Cell culture
•
Genetically engineer cell to produce desired
product and create cell line
 Recovery and Purification
•
Harvest desired component and purification
 Formulation to Distribution
http://www.gene.com/media/company-information/manufacturing 2Food
and Drug Administration. Biosimilars.
What is a biosimilar?
 A biologic shown to be “highly similar” to
the reference biologic AND has “no clinically
meaningful differences in safety and
effectiveness” from the reference product
 Offer less costly options that are proven to
be safe and effective as the reference
product
1MORROW
T, Felcone LH. Defining the difference: What Makes Biologics Unique. Biotechnology Healthcare. 2004;1(4):24-29.
and Drug Administration. Biosimilars.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Bio
similars/ (Accessed 2015 November 7)
2Food
Biosimilar Approval Pathway
Non-biologics
Biologics
• Approved under the
Food, Drug, and
Cosmetic Act
• Approved under the
Public Health Service Act
(1944)
• The Hatch-Waxman
amendment of 1984
established procedure
for generic drug
approvals
• In 2010, Affordable Care
Act amended the PHS Act
and create an
abbreviated pathway for
biosimilar approvals
much like the ANDA
pathway for generic drugs
US Food and Drug Administration. Biosimilars. 27 August 2015. Available at:
http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/def
ault.htm
Public Health Services Act
Biologics License Application
351(a)
Full evaluation of drug
(Pre clinical R&D, Phase I,II, &
III clinical trials)
Biosimilar Application
341(k)
Analytical studies, Animal data,
& Clinical data
(Each stage is head-to-head
comparison to reference
product)
US Food and Drug Administration. Biosimilars. 27 August 2015. Available at:
http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/def
ault.htm
Biologics Price Competition
& Innovation Act
Created abbreviated licensure pathway for
biologics to be approved as biosimilar
Biosimilars application must include
biosimilarity data derived from:
1. Analytical Studies (Structural and Functional Analyses)
2. Animal Studies (Toxicity, Pharmacodynamics, Pharmacokinetics)
3. Clinical Studies (Human pharmacology, immunogenicity, and
clinical comparison data)
Food and Drug Administration. Scientific ConsiderationsinDemonstratingBiosimilarity to a Reference Product. Guidance for Industry. 2015; April..
FDA defines
interchangeability as….
“An interchangeable biological product is
expected to produce the same clinical result as
the reference product in any given patient,
and for a product that is given to a patient
more than once, the risk in terms of safety and
effectiveness of alternating or switching
between the interchangeable and the
reference product is not greater than the risk
of using the reference product without
alternating or switching.”
US Food and Drug Administration. Biosimilars. 27 August 2015. Available at:
http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosi
milars/default.htm
Interchangeability
The FDA has issued information regarding the standard of “interchangeability”
 Must demonstrate the expectation of providing the same clinical response
as the reference product in any given patient
 Switching between the reference product and biosimilar must not exhibit
any diminished effect to the patient in regards to safety and efficacy
 If the FDA deems a biosimilar as “interchangeable” with the reference
product, it may substitute the reference product without the authorization
of the prescriber
Food and Drug Administration. Biosimilars Questions & Answers Regarding the Impllementation of the Biologics Price Competition & Innovation Act of 2009.
Guidance for Industry. 2015; April..
Biosimilar = generic???
Biosimilar = Interchangeable???
Interchangeable biosimilar =
generic ???
Biosimilars Labeling
March 31, 2016
The FDA issues Industry guidance on
labeling for Biosimilar products
Food and Drug Administration. Labeling for Biosimilar Products. Guidance for Industry. 2016, March 31..
Biosimilars Labeling
 Biosimilar Approval/licensure date
Biosimilarity Statement
*(defines biosimilar)
Food and Drug Administration. Labeling for Biosimilar Products. Guidance for Industry. 2016, March 31..
Biosimilars Labeling
“FDA recommends that in the biosimilar product labeling, applicants
incorporate relevant data and information from the reference product
labeling, with appropriate product specific modifications.”
“Data from clinical studies designed to support a demonstration of
biosimilarity are not likely to be relevant to a health care practitioner’s
considerations regarding safe and effective use of the biosimilar product
and potentially may cause confusion, resulting in an inaccurate
understanding of the risk-benefit profile of the product.”
Food and Drug Administration. Labeling for Biosimilar Products. Guidance for Industry. 2016, March 31..
Biosimilars Labeling
“Therefore, based on a demonstration of biosimilarity,
biosimilar product labeling should include a description of
the clinical data that supported safety and efficacy of the
reference product as described in the FDA-approved product
labeling for the reference product.”
Food and Drug Administration. Labeling for Biosimilar Products. Guidance for Industry. 2016, March 31..
Biosimilars Labeling
Proprietary name should be used in package labeling
Except….
Clinical studies or data (safety and efficacy data)
derived from studies in which the reference product is
described AND
Biosimilarity statement
Food and Drug Administration. Labeling for Biosimilar Products. Guidance for Industry. 2016, March 31..
Biosimilars Labeling
When to use the core name?
 In BBW, CI’s, AE’s, and precautions….
Food and Drug Administration. Labeling for Biosimilar Products. Guidance for Industry. 2016, March 31..
Biosimilars Labeling
 Data for Indications approved for the reference product but
not the biosimilar product will not be included in the
labeling
 Immunogenicity statement in subsection of “ADVERSE
REACTIONS” section
 Interchangeability?
Food and Drug Administration. Labeling for Biosimilar Products. Guidance for Industry. 2016, March 31..
Purple Book
It serves the same purpose as the Orange book….except for
Biologics
 Lists all approved biologics approved under 351(a) of the PHS Act
as well as their approval dates and and patent expirations
 Lists the dates that biosimilars of the reference products were
approved
 Will also list products approved as
biosimilars and interchangeability
status
Food and Drug Administration. Biosimilars Questions & Answers Regarding the Impllementation of the Biologics Price Competition &
Innovation Act of 2009. Guidance for Industry. 2015; April..
What if a biosimilar is not
approved as interchangeable
with the reference product?
How will payers treat this product?
Perception of Payers
Interchangeability?
http://www.amgenbiotech.com/resources/2015_Trends_in_Biosimilars_Report-83531R1V1.pdf
Your Perception
Efficacy
Safety
Cost Savings
http://www.amgenbiotech.com/resources/2015_Trends_in_Biosimilars_Report-83531R1V1.pdf
Your Perception
Likelihood of substitution with
biosimilar?
15% cost savings?
30%?
Interchangeability?
Perception of Prescribers
150 board certified specialty practitioners (GI, DERM,
RA, Onc., Endo.)
On March 6, 2015, the
FDA approved the 1st
Biosimilar in the US
Zarxio (Sandoz)
FDA approved biosimilar to Amgen’s
Neupogen for all 5 labeled indications
Zarxio Launched September
3rd and markets at a 15%
discount compared to the
reference product Neupogen
Zarzio Launched 2009 in Europe with
same initial 15% discounted price and now
average discount of Neupogen biosimilars in
Europe is 20-30% cost savings
Concerns
Developing AB’s to reference product….what
about biosimilar?
Most reference products patients have tried
and failed and have moved on to new
products. Will prescribers switch patients
back to reference product biosimilar?
Food and Drug Administration. Labeling for Biosimilar Products. Guidance for Industry. 2016, March 31..
Zarxio aka filgrastim-sndz
Instead of using shared non proprietary names
for biosimilars, the FDA has suggested adding a
4 letter suffix to the end of the non proprietary
name
FDA still debating if interchangeable biosimilars
will have a unique 4 consonant suffix or share
the same suffix as its reference counterpart
“FDA’s guidance documents do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency’s current
thinking on a topic and should be viewed only as
recommendations”
FDA’s proposed Rule: “Designation of Official Names and Pro per Names for Certain Biological Products” Filed August 27, 2015.
http://s3.amazonaws.com/public-inspection.federalregister.gov/2015-21382.pdf. Accessed October 7, 2015.
On April 5, 2016, the
FDA approved the 1st
MAB Biosimilar in the
US
Infelctra (Hospira/Pfizer)
FDA approved biosimilar to
Janssen’s Remicade for 7 of 8
labeled indications
Infliximab-dyyb
Approved for all but 1
indication – pediatric UC
Only comparison studies
were with RA and AS
Growth of filgrastim
biosimilars in Europe
http://www.cbinet.com/sites/default/files/files/WorkshopBPres1.pdf
Growth of filgrastim
biosimilars in Europe
https://www.ftc.gov/system/files/documents/public_events/FollowOn%20Biologics%20Workshop%3A%20Impact%20of%20Recent%20Legislative%20and%20Regulatory%20Naming%20Proposals%20on%20Competition/ramachandr
a.pdf
Increase in access to
biologic regimens
Cost savings related to
biosimilars in combination
with reduced costs of
reference products to
compete
Increased access may offset total
savings due to biosimilars
http://www.rand.org/content/dam/rand/pubs/perspectives/PE100/PE127/RAND_PE127.pdf
Estimated Cost Savings
of Biosimilars
Express
Scripts
•Project potentially $250
billion in savings over
next 10 years if 11 of the
likeliest biosimilars enter
the market
Congressional • Estimate 10 year
Budget Office
savings to be only
$25 billion
http://americanactionforum.org/research/the-new-frontier-of-pharmaceuticals-biosimilars
Dependent Variables
Acceptance of prescribers and patients
Reference product push-back
Final FDA mandates
Acceptance of extrapolation
13 Andrew W. Mulcahy, Zachary Predmore, and Soeren Mattke, “The Cost Savings Potential of Biosimilar Drugs in the United States,” RAND Corporation,
2014, www.rand.org/t/PE127.
Extrapolation
Infliximab (Remicade) biosimilar approved in
Europe in 2013 for all 8 indications by
Celltrion/Hospira
Marked the 1st MAB biosimilar approved
Pre-approval clinical studies were done for RA and
AS indications only then extrapolated data as basis
for approvals for the other 6 indications
Post-marketing studies confirming biosimilarity
and extrapolation for other indications
Weise M, Kurki P, Wolff-holz E, Bielsky MC, Schneider CK. Biosimilars: the science of extrapolation. Blood. 2014;124(22):3191-6.
Biologic manufacturers update the
manufacturing process throughout the life cycle
of the drug
Regulations are set in place to ensure that
despite changes in the manufacturing process,
the product remains
highly similar and
will predictively
reproduce the same
clinical and safety
results
1McCamish
M, Woollett G. The Continuum of Comparability Extends to Biosimilarity: How Much Is Enough and What Clinical Data Are Necessary?Clinical Pharmacology and Therapeutics. 2013;93(4):315317. doi:10.1038/clpt.2013.17.
2Schneider CK. Biosimilars in rheumatology: the wind of change. Ann Rheum Dis. 2013;72(3):315-8.
The determination of comparability within these
regulations have not been primarily based on
clinical and non-clinical data but rather
physicochemical and analytical comparisons
Manufacturing process changes are the norm
Batch to batch biosimilarity, not identical
1McCamish M,
Woollett G. The Continuum of Comparability Extends to Biosimilarity: How Much Is Enough and What Clinical Data Are Necessary?Clinical
Pharmacology and Therapeutics. 2013;93(4):315-317. doi:10.1038/clpt.2013.17.
2Schneider CK. Biosimilars in rheumatology: the wind of change. Ann Rheum Dis. 2013;72(3):315-8.
On November 5, 2015,
the FDA rejects
Hospira’s EPO
Bisomiliar application
 Retacrit was approved in Europe in 2008
SANDOZ
Currently 5 biosimilar products in clinical trials in the
US
• Humira, Enbrel, Rituxan (2), Epogen (2), Neulasta
• 6 of 7 in phase III trials
• Had first biosimilar approval in the US with Zarxio
(filgrastim)
Filgrastrim
Reference product: Neupogen (Amgen)
(Sandoz)
FDA approved biosimilar 3/2015
(Apotex/Intas)
FDA accepted application in 2/2015
8 Filgrastim biosimilar products currently approved in
Europe
Peg-filgrastim
 Reference product: Neulasta (Amgen)
(Apotex)
FDA accepts application 12/2014
Epoetin Alfa
Reference product: Procrit (Janssen) & Epogen (Amgen)
(Hospira)
FDA rejects application 11/2015
(Sandoz)
Biosimilars
& Medicare
Less than 1% of the retiree population >65
utilize biologics
However, 7-7.5% of healthcare spending for this
population is represented by biologics
http://us.milliman.com/uploadedFiles/insight/2015/understanding-biosimilars.pdf
CMS Addresses Biosimilars
CMS may add biosimilars and/or remove
reference product from formulary at any time
Excludes approvals under 351(k) from the CGDP
during coverage gap
 Biosimilars still considered subject to higher
maximum copays
Centers for Medicare & Medicaid Services (CMS). 2014 ASP NDC HCPCS Crosswalk. 30 September 2014. Available at: http://www.cms.gov
/Medicare/Medicare-Fee-for-Service-Part-B-Drugs/McrPartBDrugAvgSalesPrice/2014ASPFiles.html. Accessed December 19, 2014.
Product Reimbursement
under Medicare B
 Initially CMS ruled that Medicare will pay 106% of WAC until ASP
data is available for the Biosimilar product
Once ASP available, reimbursement will be ASP of biosimilar
products + 6% of ASP for reference product
Designed to drive biosimilar prescribing
State Regulations on
Biosimilars
Address substitution regulations of FDA
approved interchangeable biosimilars
Requirements of notification of substitution to
prescriber and/or patient
Proof of medical necessity requirements
(Tennessee)
Record keeping of substitutions
Available at: http://www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx.
Accessed November 16, 2015.
Available at: http://www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx.
Accessed November 16, 2015.
Georgia Pharmacy Law
Pharmacist may substitute an interchangeable
biologic product
Shall dispense the lowest retail priced
interchangeable product in stock
Must record substitution on original Rx with
identity of biosimilar and it’s manufacturer
2015 Ga. Laws 2-42 tit.26, ch.4, art. 1.
Georgia Pharmacy Law
continued…
Must indicate substitution on auxiliary label
Brand necessary still dictates reference
product prescribed must be dispensed
Must communicate to prescriber that
substitution has occurred with identity and
manufacturer of interchangeable product
2015 Ga. Laws 2-42 tit.26, ch.4, art. 1.
Pharmacovigilence
Must be able to identify the product(s) the
patient has received
Must have consistent, effective naming
system in place to avoid substitution errors
and correct dispensing of the prescribed
product (INN and distinct brand name)
1Pineda
C, Caballero-uribe CV, De oliveira MG, et al. Recommendations on how to ensure the safety and effectiveness of biosimilars in Latin America: a
point of view. Clin Rheumatol. 2015;34(4):635-40.
2Grampp G, Felix T. Pharmacovigilance Considerations for Biosimilars in the USA. BioDrugs. 2015;29(5):309-21.
Pharmacovigilence
System in place for reporting adverse events and
effectively determining whether such event
occurred from biosimilar or reference product
State laws on substitution record keeping
1Pineda
C, Caballero-uribe CV, De oliveira MG, et al. Recommendations on how to ensure the safety and effectiveness of biosimilars in Latin America: a
point of view. Clin Rheumatol. 2015;34(4):635-40.
2Grampp G, Felix T. Pharmacovigilance Considerations for Biosimilars in the USA. BioDrugs. 2015;29(5):309-21.
What to expect moving
Forward….
Final specific FDA considerations in demonstrating
interchangeability
Biosimilar naming
More states enacting regulations regarding biosimilars
More Biosimilars approved
Education is Key!!!
Make Me a Match
• Remicade
• Cimzia
• Plegridy
• Opdivo
• Stelara
• Cosentyx
• Praluent
•
•
•
•
•
•
•
•
•
•
Ulcerative Colitis
Crohn’s Disease
Rheaumatoid Arthritis
Psoriatic Arthritis
Psoriasis
Multiple Sclerosis
Ankylosing spondylitis
Oncology
Familial Hypercholesterolemia
Type II Diabetes