Biosimilar Trastuzumab: The Heritage Trial Hope Rug… · Currently Approved Oncology Biosimilars...
Transcript of Biosimilar Trastuzumab: The Heritage Trial Hope Rug… · Currently Approved Oncology Biosimilars...
Biosimilar Trastuzumab: The Heritage Trial
Hope S. Rugo, MDProfessor of MedicineDirector, Breast Oncology and Clinical Trials EducationUniversity of California San Francisco Comprehensive Cancer Center
Differences Between Chemical Drugs and Biologics
Chemical Drugs Biologics
Size Small, low molecular weight Large, high molecular weight
Structure Simple, well-defined Complex, heterogeneous
Manufacturing• Reproducible chemical reactions
• Identical copies can be made
• Living cells or organisms
• Impossible to ensure identical copies
Characterization Completely characterizedImpossible to fully characterize molecular composition
Stability StableUnstable, sensitive to external conditions
Immunogenicity Mostly nonimmunogenic Immunogenic
Declerck PJ. Generics and Biosimilars Journal. 2012;1(1)13-16.
• Biologics represent approximately 50% of the pharmaceutical market in oncology
• Biologics play a critical role in clinical care:
– Supportive care
• Myeloid growth factors
• Erythropoietin-stimulating agents
– Active therapy
• Monoclonal antibodies
• Antibody-drug conjugates
• Cytokines
Nowicki M. Kidney Blood Press Res. 2007;30:267-272.
Biologics in Oncology
1. European Medicines Agency. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. London, UK: EMA; 2014. 2. US Food and Drug Administration. Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. Silver Spring, MD: FDA; 2015. 3. World Health Organization. Guidelines on evaluation of similar biotherapeutic products (SBPs). Geneva, Switzerland: WHO; 2014. http://www.who.int/biologicals/areas/biological_therapeutics/BIOTHERAPEUTICS_FOR_WEB_22APRIL2010.pdf?ua=1. Accessed January 10, 2018.
What Is a Biosimilar?
Biosimilars are medicinal products that have received regulatory approval based on an overall assessment
of similarity to an existing biologic medicine1-3
Highly similar to an approved biologic product (reference product)
No clinically meaningful differences in terms of quality, safety, and effectiveness from the reference
product
Biosimilar ProductReference Product
IMS Global Oncology report . https://morningconsult.com/wp-content/uploads/2016/06/IMS-Institute-Global-Oncology-Report-05.31.16.pdf.
https://www.iqvia.com/institute/reports/the-global-use-of-medicine-in-2019-and-outlook-to-2023
Biologics accounted for >55% of antineoplastic drug costs in 2011 in the US but just over
half (55%) of new targeted therapies are available in pharmerging countries
Access To New Oncologic Treatments VariesWidely Across the Globe
2015 Availability of New Oncology Medicines Launched 2010-2014
The Hope: Effective and safe biosimilars will help to alleviate the substantial burden on healthcare systems
from biologic medications by stimulating price competition and improving patient access to
important and life-saving treatments
PD, pharmacodynamics; PK, pharmacokinetics.
1. Schneider CK, et al. Nat Biotechnol. 2012;30:1179-1185. 2. McCamish M. Presented at EMA Workshop on Biosimilars; London; October 2013. 3. Berghout A. Biologicals. 2011;39:293-296. 4.
US Food and Drug Administration. Abbreviated New Drug Applications (ANDA): Generics.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/. Accessed January 3, 2016.
Development PathwaysStandard Biologics1,2
Nonclinical
Clinical pharmacology
PK/PD
Analytical
Clinicalstudies
Analytical
Bio-equivalence
in HealthyVolunteers
Small Molecule Generics1,4
Biosimilars1-3
Nonclinical
Comparative clinical
pharmacologyPK/PD
Analytical
Comparative Clinicalstudies
Confirm safety profile and efficacy in a disease population (dose ranging not necessary)
The Goal of Biosimilar Development Is to Demonstrate That There Are No Clinically
Meaningful Differences Based on the Totality of Evidence, Not to Reestablish Benefit1-4
Reference Biologics
NOT Identical
Reference BiologicsHighly Similar
Manufacturing/Process ChangesFDA: Demonstration of Comparability
Biosimilars
Reference Biologics
Variations Over Time
IdenticalGenerics Small Molecule Drugs
Generics
Biosimilars
Highly Similar
No Adverse Impact Upon Safety or Efficacy
of the Drug Product
Identical Copies of Biologics Cannot Be Made
• Variations in the reference product quality attributes over time can be used to evaluate comparability of the biosimilar product
McCamish M, Woollett G. MAbs. 2011;3(2):209-217.
Variation of Biologic Quality Attributes Following Expected Manufacturing Changes
Reference product
at approval
Range of variation of biologic
quality attributes
Reference product
following first postapproval
manufacturing change
Biosimilar product
Acceptable range of variation
Reference product
following second
postapproval manufacturing
change
Biosimilar product
Variation of Biologic Quality Attributes Over Time
Drifts in ADCC-Related Quality Attributes of Originator Trastuzumab:
Impact on Development of a Trastuzumab Biosimilar
Kim S, et al. MAbs. 2017; 9(4): 704–714.
trastuzumab
trastuzumab
trastuzumab
trastuzumab
trastuzumab
trastuzumab
trastuzumab
trastuzumab
Clinical Requirements
• At least one clinical pharmacokinetic study for establishing
bioequivalence to the reference product
• At least one study of clinical safety, efficacy, and immunogenicity to
establish clinical equivalence
– Typically performed in the most sensitive population
– Establishes similarity in efficacy
– Immunogenicity and safety data
• Additional clinical trials as necessary
– To rule out residual uncertainty
PK, pharmacokinetics; PD, pharmacodynamics.
1.. Weise M, et al. Blood. 2012;120(26):5111-5117. 2 Windisch J. Int J Clin Rheumatol. 2015;10(6):1-10. 3. US Food and Drug Administration. Scientific Considerations in Demonstrating Biosimilarityto a Reference Product: Guidance for Industry. Silver Spring, MD: FDA; April 2015
Extrapolation: After Biosimilarity Is Established, AllowsPotential Approval for Nonstudied Indications1-3
Biosimilarity Established Basedon Totality of Evidence1,2 Extrapolation for Biosimilars
Extrapolation builds on the thorough analysis of similarity between the biosimilar and reference biologic
supported by the scientific evidence generated in robust analytical, nonclinical, and clinical comparability
studies. Together with the well-known understanding of the reference biologic, this evidence is carefully
analyzed to support scientific justification of extrapolated indications.1,2
Comparative Clinical Studies
Comparative Clinical Pharmacology (PK/PD)
Comparative Nonclinical
Comparative Analytical
SCIENTIFIC JUSTIFICATION to support extrapolation to each
approved indication of the reference biologic1,3
Extrapolation indications
MOA, Mechanism of action
1. Weise M, et al. Blood. 2014;124(22):3191-3196. 2. European Medicines Agency. Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Non-clinical and Clinical Issues. London, UK: EMA; 2014. 3. US Food and Drug Administration. Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Guidance for Industry. Silver Spring, MD: FDA; April 2015.
The Basis for Scientific Justification
Experience With the Reference Biologic1
• The molecular structure of the reference biologic forms the basis for its clinical effect
• Established clinical profile may define any differences between indications
The Totality of Evidence1,2
• Demonstrates highly similar structure and function of the biosimilar and the reference biologic molecules
• Clinical efficacy, safety, and immunogenicity in a key indication
2,3
Currently Approved Oncology Biosimilars in the United States….
And More in Development!Product Approval Date
trastuzumab-anns June 2019
trastuzumab-qyyp March 2019
trastuzumab-dttb January 2019
trastuzumab-pkrb December 2018
rituximab-abbs November 2018
pegfilgrastim-cbqv November 2018
filgrastim-aafi July 2018
pegfilgrastim-jmdb June 2018
trastuzumab-dkst December 2017
bevacizumab-awwb September 2017
filgrastim-sndz March 2015
U.S. Food and Drug Administration. Biosimilars > Biosimilar Product Information. https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/ucm580432.htm. Accessed June 20, 2019.
Integration Into Cancer Care
• Supportive care biosimilars (eg, filgrastim, peg-filgrastim) are acceptable to
clinicians and patients
– Biosimilar filgrastim in active clinical use
• Biosimilar cancer therapeutics (eg, rituximab, trastuzumab) have a higher bar
for acceptance
– Clinical trials with a short-term efficacy endpoint in a highly sensitive population
– PK and PD endpoints
– Immunogenicity
– Safety
– Post-approval surveillance
Comparative Clinical Studies
• Purpose: Exclude any clinically relevant differences
between the biosimilar and the reference product and
to address any residual uncertainly about biosimilarity
• Conducted stepwise
– Immunogenicity studies followed by comparative clinical
efficacy and safety
– Extrapolation is a critical concept
Selecting a Valid Clinical Endpoint• Critical and challenging for biosimilars
• Sensitive endpoints are recommended
Patient Criteria• Overall survivalDisease Criteria• Objective response rate• Disease free survival• Disease free progression• Pathological complete response
Endpoints for biosimilar clinical trials• Clinically relevant, short-term objective
measure able to detect differences• Continuous endpoints may be preferred over
binary endpoints• Length of the study should be sufficient to
allow for adequate safety and immunogenicity assessments
EMA-2. Committee for Medicinal Products for Human Use (CHMP). Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Non-clinical and Clinical Issues. London: European Medicines Agency; 2014.WHO-2. WHO Guidelines on evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs), 2016. He K, et al. Clin Cancer Res. 2016 Nov 1;22(21):5167-5170. Gourgou-Bourgade S,et al. Ann Oncol. 2015;26(5):873-9. Fiteni F, et al. J Visc Surg. 2014;151(1):17-22. Pivot X, et al. 2017. Available at: http://meetinglibrary.asco.org/record/145553/abstract.
Optimal Clinical Trial Setting?
• Most treatment naïve
• Long drug exposure for a majority to assess safety and immunogenicity
• Highly sensitive endpoint (ORR) that allows evaluation of secondary endpoints (PFS/OS) in realistic time frame
• ORR correlates with PFS and OS in HER2+ disease
• All treatment naïve
• Short-term endpoint of pCR, one year drug exposure
• DFS and OS are long-term endpoints
• Post surgery treatment may impact long-term endpoints
First-line metastatic trials Neoadjuvant trials
Trastuzumab Biosimilars: The New Frontier
• Over-expression of HER2 implicated in the pathophysiology of ~ 25%
of breast and 18% gastric and gastroesophageal tumors
• Trastuzumab has changed the treatment course for HER2+ tumors
– In metastatic breast cancer, improves PFS, OS, and ORR
– In early stage breast cancer, improves DFS and OS
– As neoadjuvant therapy, improves pCR and DFS rates
– Improves PFS, OS, and ORR in metastatic gastric cancer
– Gold standard as treatment of early and late-stage HER2+ breast
cancer
– Is well tolerated with modest and manageable toxicity
HERITAGE: First-line Trastuzumab vs Biosimilar MYL-1401O
in HER2+ Metastatic Breast Cancer
• Primary endpoint (week 24): ORR
• Secondary endpoints (week 48): tumor progression rate, PFS, OS
HER2+ metastatic breast cancer, no prior tx in
metastatic setting. Stratify for time to mets, ER/PR status, and taxane used (N = 500)
MYL-1401O 6 mg/kg IV Q3W* + taxane† for minimum of 8 cycles
(n = 249)
Trastuzumab 6 mg/kg IV Q3W* + taxane† for minimum of 8 cycles
(n = 251)
Part 1Part 2
Continue assigned therapy if achieved at least SD
MYL-1401O 6 mg/kg IV Q3W* + taxane†
Trastuzumab 6 mg/kg IV Q3W* + taxane†
Week 24
Until PD, unacceptable
toxicity, or death
Multicenter, Randomized, Double-blind Phase III Equivalence Study
*After usual loading dose. †Physician choice of docetaxel or paclitaxel
Rugo HS, et al. JAMA. 2017;317:37-47 and ASCO 2018, Waller et al, ASCO 2019
Designed per FDA and EMA guidelines to detect any potentially clinically meaningful differences between biosimilar and originator trastuzumab
Key Baseline and Disease Characteristics: Comparable Between Treatment Groups
Patient characteristicsTrastuzumab-dkst
N=230Trastuzumab
N=228Age category, n(%)
<50 years 74 (32.2) 86 (37.7)≥50 years 156 (67.8) 142 (62.3)
Race, n(%)Asian 70 (30.4) 72 (31.6)Black 1 (0.4) 2 (0.9)White 159 (69.1) 154 (67.5)
Prior treatment (adjuvant), n(%)Trastuzumab 22 (9.6) 16 (7.0)Taxane 46 (20.0) 42 (18.4)
Assigned taxane, n(%)Docetaxel 193 (83.9) 192 (84.2)Paclitaxel 35 (15.2) 32 (14.0)
Visceral metastases, n(%)Yes 172 (74.8) 185 (81.1)No 58 (25.2) 43 (18.9)
Primary Endpoint:
Ratio of ORR (90% CI) at Week 24 Within the Prespecified Equivalence
Margin Supports Similar Efficacy
ITT, intention-to-treat; ORR, overall response rate; RECIST, Response Evaluation Criteria In Solid Tumors. aRatio of best ORR (defined as a complete or partial response per RECIST 1.1) by week 24 based on cumulative assessment done by a single, central, blinded oncologist.
Rugo et al. JAMA. 2017;317:37-47 and ASCO 2018
Parameter
Trastuzumab-dkst N=230
Trastuzumab N=228
ORR, n (%) 161 (70.0) 146 (64.0)
Ratio of ORR (90% CI) 1.09 (0.981, 1.218)
Difference in ORR (90% CI) 6.00 (-1.26,13.11)
Best ORR at week 24 in the ITT populationa
0.7 0.9 1.1 1.3
Ratio of ORR (90% CI) 1.09 (0.981, 1.218)
Prespecified equivalence margin
0.81 1.24
Stratified by taxane, tumor progression, tumor endocrine status.
Rugo HS, et al. JAMA. 2017;317:37-47 and ASCO 2018
Similar Efficacy Between Trastuzumab-dkst and Trastuzumab
Observed Through 48 Weeks
aStratified by assigned taxane, tumor progression, and tumor endocrine status. bAssessments are ongoing and OS will be calculated after 240
deaths or 36 months.
Progression-free survival Overall survivalb
Trastuzumab-dkst Trastuzumab Trastuzumab-dkst Trastuzumab
Median (95% CI) 11.1 (8.81-11.20)
11.1 (8.60-11.20)
NE NE
Log-rank P value 0.842 + censored 0.131 + censored
Stratified hazard ratio (95% CI)a 0.95 (0.714-1.251) 0.61 (0.360-1.039)
P value 0.694 —
NE, not estimable; OS, overall survival.
Similar Efficacy Between Trastuzumab-dkst and
Trastuzumab Observed Through 48 WeeksProgression-Free Survival Overall Survival (immature)
Trastuzumab-dkst
Log-rank P=0.131 + Censored
1.0
0.8
0.6
0.4
0.2
0.0
Surv
ival
pro
bab
ility
0 4 8 12 16 20
Time, weeks
++++++++++++++++ +++++++++++++++++++
++++
+++ + ++++++++++++ ++ + + ++++++ + ++ +++ +++++++ ++ +++ ++ ++++
++ +++
+ ++++
+
24 28 32 36 40 44 48 52
+++++++++ +
Trastuzumab
Log-rank P=0.842 + Censored
1.0
0.8
0.6
0.4
0.2
0.0
Surv
ival
pro
bab
ility
0 4 8 12 16 20
Time, weeks
24 28 32 36 40 44 48 52
++
+++++++
+++ +++++ + +++++++ ++ + +++++ +++ + ++ +++
+++++++ +
+ ++++++ ++++++++++ + +
++++
+++++ + ++ + + ++
+++
+++
+
Trastuzumab
Trastuzumab-dkst
PFS at Week 48 Correlates with ORR at Week 24
CR, complete response; ORR, overall response rate; PFS, progression-free survival; PR, partial response. Rugo et al, ASCO 2018
• At week 24, 1.3% and 0% of patients demonstrated CR, and 68.3% and 64.0% demonstrated PR, with trastuzumab-dkst and trastuzumab, respectively
• At week 48– An additional 2 patients (1 per group) demonstrated CR and an additional 5 patients demonstrated PR in the trastuzumab group– The confirmed ORR is 70.0% and 66.7% with trastuzumab-dkst and trastuzumab, respectively
Responder
Non-responder
ORR at week 24 with PFS at week 48
50
40
30
20
10
0
Responder Nonresponder
161N 146 69 82
++++++
PFS
at
we
ek
48
, we
eks
ORR at week 24
Trastuzumab-dkst + taxane
Trastuzumab + taxane
ORR at week 24 with PFS probability
Biserial correlation coefficient in the total sample is rb = 0.752
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
PFS
pro
bab
ility
0 10 20 30 40 50
Weeks since randomization
+ +++++ +++++++ + +
+++++++
++++ +++ + +++++++++
+++++++++
+++++
++
+
+++++++
+ +++ + ++++ ++
+
+
+++ ++ ++
+
+++
+++++++++++++
+++++
++
+++
+++
+ Censored
trastuzumab
trastuzumab-dkst
trastuzumab
trastuzumab-dkst
Further Lines of Therapy
Trastuzumab-dkstN=230
TrastuzumabN=228
Systemic therapy, % 38.2 32.6
Antineoplastic agents 34.6 29.9
Endocrine therapy 7.5 10.3
Most commonly used agents, %
Capecitabine 23.2 16.1
Trastuzumab 9.6 10.3
Cyclophosphamide 8.8 8.0
Lapatinib 8.3 4.9
Other HER2-targeted agents, %
Trastuzumab emtansine 1.8 2.2
Pertuzumab 0.4 0
HERITAGE: Overall Survival at 36 Months
Waller CF, et al. Presented at: 2019 American Society of Clinical Oncology. Abstract 1021.
Similar Final Efficacy Between Trastuzumab-dkst and
Trastuzumab Observed Through 36 Months
Progression-free survival Overall survival
Trastuzumab-dkstN=230
TrastuzumabN=228
Trastuzumab-dkstN=230
TrastuzumabN=228
Events 148 142 109 114
Median (95% CI) 11.1 (8.72, 13.78) 11.1 (8.95, 12.67) 35.0 (26.75, 39.88) 30.2 (25.00, 39.86)
Log-rank P value 0.864 0.427
Unstratified hazard ratio (95% CI)
0.98 (0.78, 1.24) 0.90 (0.69, 1.17)
HERITAGE: Safety Profile at Week 24Endpoint
MYL-1401O + Taxane(n = 247)
Trastuzumab + Taxane(n = 246)
Serious AE, % ≥ 1 serious AE Neutropenia Neutropenia with fever Leukopenia Pneumonia
38.127.54.51.61.6
36.225.24.14.92.0
Deaths due to serious AEs, n 4* 4†
Median LFEV values, % (range) Baseline Wk 24 Change from BL to Wk 24
64.0 (51 to 82)63.5 (50 to 81)-1.0 (-13 to 21)
63.0 (51 to 84)63.0 (41 to 82)-1.0 (-19 to 13)
Rugo HS et al. JAMA. 2017;317:37-47.
Incidence of AEs Is Low During Monotherapy
AEs, patients, %
Combination therapy: weeks 1-24 Monotherapy: weeks 24-48Trastuzumab-dkst
+ taxaneN=247
Trastuzumab+ taxaneN=246
Trastuzumab-dkstN=179
TrastuzumabN=163
Neutropenia 57.5 53.3 1.1 2.5Asthenia 21.9 16.3 2.8 1.8Nausea 19.8 13.8 2.2 2.5Edema peripheral 14.2 11.4 0.6 1.8Arthralgia 12.1 4.5 2.8 1.2Vomiting 10.5 7.7 1.7 3.1Urinary tract infection 8.5 6.5 0.6 2.5Upper respiratory tract infection 6.1 1.6 2.2 1.2Infusion-related reaction 6.9 4.5 0 0.6
AE, adverse event; TEAE, treatment-emergent AE.
Only 513 of 5015 total TEAEs (10%) started during monotherapy treatment
HERITAGE: Immunogenicity and Population PK
• Immunogenicity was similarly low for both MYL-1401O and trastuzumab arms
– Overall antidrug antibody rates: 2.4% vs 2.8%, respectively
– Median titer in antibody-positive pts: 2.5 vs 2.3, respectively
• Trough Cmin comparable between arms at Wk 15 (cycle 6)
– Ratio of geometric LSMs: 103.88% (90% CI: 93.7% to 115.11%)
• Population pharmacokinetics similar between MYL-1401O and trastuzumab arms
– Dose-normalized mean Cmax: 0.4321 vs 0.4196 µg/mL/mg, respectively
– Dose-normalized mean AUC: 98.350 vs 94.391 μg·d/mL/mg, respectively
Rugo HS et al. JAMA. 2017;317:37-47.
HERITAGE Study Data in Clinical PerspectiveHERITAGE STUDY HISTORICAL DATA
Endpoint MYL-1401O Herceptin1st line HER2+
MBC
ORR 24 Weeks (Primary) 70% 64% 55-69%1-5
ORR ratio (90% CI): FDA Requirement 1.09 (0.981, 1.218) N/A
ORR difference (95% CI): EMA Requirement 6.0% (-2.64%, 14.45%) N/A
Time to Progression (TTP) 48 Weeks 11.1 Months 11.1 Months11.3 -12.4 Months 1-
5
Overall Survival 48 Weeks 89.1% 85.1% 75%-89% 1-5
Safety & Toxicity Comparable Consistent
Immunogenicity 3.9% 4.4% 3.4%6-7.1%7
Exposure Comparable Consistent
1Slamon DJ, et al. N Engl J Med. 2001;344:783-792., 2Mass RD, et al. Clin Breast CA. 2005;6(3):240-246., 3Marty M, et al. J Clin Oncol. 2005;23(19):4265-4274. 4Baselga J, et al. N Engl J Med. 2012;366:109-119., 5Swain et al, N Engl J Med. 2015;372:724-734. 6Hegg R, et al. Presented at: 2012 ESMO Congress. Abstracts 273P, 7Jackisch C, et al. Annals of Oncology. 2015;26:320-325.
Summary of Phase III Trials for Trastuzumab Biosimilars
SB-3(Trastuzumab-dttb)
ABP-980(Trastuzumab-anns)
CT-P6 (Trastuzumab-pkrb)
MYL-1401O(Trastuzumab-dkst)
PF-05280014(Trastuzumab-qyyp)
Trial NCT02149524 NCT01901146 NCT02162667 NCT02472964 NCT1989676
Disease EBC EBC EBC and Metastatic
Metastatic NeoadjuvantMetastatic
No. of patients 800 725 549 500 225/707
Stage of development
FDA approved(January 2019)
FDA approved(June 2019)
FDA approved(December 2018)
FDA approved(December 2017)
FDA approved (March 2019)
EBC: Early breast cancer
Pharmacovigilance• Safety – As more biosimilars are marketed and market uptake increases, real-world safety and
efficacy data will emerge.
– Post-marketing pharmacovigilance efforts may likely be utilized to monitor safety and efficacy of
biosimilars.
– European Medicines Agency mandated pharmacovigilance monitoring for all approved biosimilars
approved.
• As a result, the European experience, with over 400 million patient days with biosimilars,
suggests that biosimilars would satisfy lingering safety concerns
– There are NO provisions in the Biologics Price Competition and Innovation Act (BPCIA) for
pharmacovigilance plans of biosimilars.
– FDA interchangeability guidance document refers back to documents for all products
• Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment (March 2005)
• Postmarketing Adverse Experience Reporting for Human Drug and Licensed Biological Products: Clarification of
What to Report (August 1997)
European_Medicines_Agency.Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. 2014; Rifkin RM, Peck SR. J Oncol Pract. 2017;13(9_suppl):24s-31s; Grampp G, Felix T. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy. 2015; 29: 309–21; AMCP Task Force on Biosimilar Collective Intelligence Systems. Journal of managed care & specialty pharmacy, 2015; 21: 23–34; FDA. Considerations in Demonstrating Interchangeability With a Reference Product Guidance for Industry. May 2019.
Unique Issues Relevant to Biosimilars
• Extrapolation
• Interchangeability
• Naming
Adalimumab-atto
Etanercept-szzs
Filgrastim-sndz*
Infliximab-abda
Bevacizumb-awwb
Infliximab-dyyb
Adalimumab-adbm
Pegfilgrastim-cbqv
Nonproprietary naming of biological products: guidance for industry. FDA.gov. March 2019.
*The suffix –sndz was named prior to the FDA-designation for biosimilar suffixes
Core name FDA-designated suffix must have: No recognizable meaning, 4 letters and lowercase
BOPA, British Oncology Pharmacy Association; EORTC, European Organisation for Research and Treatment of Cancer; FN, febrile neutropenia; NHS, National Health Service.
1. Aapro MS, et al. Eur J Cancer. 2011;47(1):8-32. 2. NHS guidelines. http://www.arden.nhs.uk/mf.ashx? ID=8817fd0e-e263-431a-90d1-b2fdb8732260. Accessed May 3, 2017. 3. Smith TJ, et al. J Clin Oncol. 2015;33; doi:10.1200/JCO.2015.62.3488. 4. Klastersky J, et al. Ann Oncol. 2016;27(suppl 5):v111-v118. 5. Tabernero J, et al. ESMO Open. 2016;1:e000142. doi:10.1136/esmoopen-2016-000142. 6. British Oncology Pharmacy Association. Guidelines on implementation of biosimilar monoclonal antibodies. February 5, 2017. 7. Lyman GH, et al. J Clin Oncol. 2018:JCO2017774893. doi:10.1200/JCO.2017.77.4893. [Epub ahead of print].
Impact of Biosimilars: Introduction of Biosimilars Into Treatment Guidelines
• Biosimilar products included in guidelines for the prevention of treatment-related neutropenia
NHS UPDATED GUIDELINES2
• Biosimilar products included in guidelines for the use of biosimilar monoclonal antibodies at the pharmacy
• Use for all commissioned indications, provided pharmacovigilance safeguards are in place
2010 2011 2012 2013 2014 2015 2016 2017 2018
BOPA GUIDELINES ON IMPLEMENTATION OF mABSAT PHARMACY6
Biosimilar products provide opportunity to both obtain desired outcomes and manage the cost of care for patients with cancer
ASCO POSITION STATEMENT7
• Biosimilar products included in guidelines as options to prevent FN and FN-related complications, where indicated
• Biosimilar products included in guidelines recommended for the prevention of treatment-related FN, where indicated
• Biosimilar products included in guidelines recommended for the prevention of treatment-related FN, where indicated
• ESMO endorses incorporating biosimilars into value framework
EORTC UPDATED GUIDELINES1
ASCO CLINICAL PRACTICE GUIDELINES3
ESMO CLINICAL PRACTICE GUIDELINES4 AND POSITION PAPER FOR ONCOLOGY BIOSIMILARS5
Lyman GH et al. J Clin Oncol. 2018;36(12):1260-1265.
Biosimilars Have The Potential To Decrease The Overall Cost Of Care For Complex Medical Conditions: ASCO Statement
Potential of biosimilars for patients, payers, and providers1-3
Summary • The goals of the biosimilar clinical trial program are to demonstrate similar
efficacy and safety compared to the reference product and to address residual uncertainty—not to re-establish benefit
• Experience with biosimilars has resulted in their introduction into multiple treatment guidelines and position statements about their use and clinical value
• Biosimilars may offer a variety of potential benefits to patients, payers, and health care providers, including:– Additional treatment choices at potentially lower cost to the health care system
– Increased access to biologics, which may lead to improved overall health outcomes
– Possible savings and efficiencies to the health care system
– A variety of therapeutic options
Biosimilars:
Improving Access to Biologic Therapy Worldwide