Biosimilar and drug repositioning

Giuseppe Curigliano MD, PhD University of Milano and European Institute of Oncology

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

EPAR. http://www.ema.europa.eu/ema/index.jsp?mid=WC0b01ac058001d124&searchType=name&taxonomyPath=&genericsKeywordSearch=Submit&searchGenericT. ype=biosimilars&keyword=biosimilar&alreadyLoaded=true&curl=pages%2Fmedicines%2Flanding%2Fepar_search.jsp&status=Authorised&treeNumber=&searchTab=searchByAuthType&pageNo=1. Accessed May 3, 2107.

32 Biosimilar Products Are Currently Approved by the EMA for Use

Biosimilar Landscape in Europe

INN Number of Products Approval

Adalimumab 2 Mar-17

Enoxaparin sodium 2 Sep-16

Epoetin alpha 3 Aug-07

Epoetin zeta 2 Dec-07

Etanercept 1 Jan- 16

Filgrastim 7 Sep-08 to Sep-14

Follitropin alfa 2 Sep-13, Mar-14

Infliximab 3 Sep-13, May -16

Insulin glargine 2 Sep-14, April-17

Rituximab 1 Feb-17

Somatropin 1 Apr-06

Trastuzumab 2 Dec-17

A list of biosimilars approved by EMA as of March, 2018

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

EMA. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2017/04/WC500225535.pdf. Accessed May 3, 2017.

18 additional biosimilar applications are currently under review by the EMA: One approved

Biosimilar Landscape in Europe (cont)

Common Name

Number of Applications

Adalimumab 2

Bevacizumab 2

Etanercept 1

Insulin glargine

1

Insulin lispro 1

Pegfilgrastim 2

Rituximab 5

Trastuzumab 3

A list of biosimilars under review by EMA as of March, 2018

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

What is a biosimilar?

Issued By Definition

WHO

A biotherapeutic product similar to an already licensed

reference biotherapeutic product in terms of quality, safety,

and efficacy

US FDA

A product highly similar to the reference product without

clinically meaningful differences in safety, purity, and

potency

EMA

A biosimilar is a product that demonstrates similarity to the

reference medicinal product in terms of quality

characteristics, biological activity, safety, and efficacy,

based on a comprehensive comparability exercise

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Generic and biosimilar

Small-molecule Drug Biologic Drug

Produced from • Chemical synthesis • Living systems (eg, cultured animal and plant cells)

Characterization • Adequately characterized

with limited physicochemical methods

• Comprehensive physicochemical analysis and

bioassays necessary

Manufacturing • Easy to reproduce • More sensitive to manufacturing conditions

Safety Considerations

• Target-specific and off-target toxicity

• Target-specific and off-target toxicity

• Immunosuppression and immunogenicity reactions

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Generic and biosimilar

• Generics

Synthetic (chemistry)

Small, simple, uniform

Predictable, easy to characterize

• Biosimilar

Biosynthetic (living organisms)

Large, complex, heterogenous

3D structure more perturbable

Difficult to fully characterize

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Generic and biosimilar

Small-Molecule Drug

Herceptin® (trastuzumab)

Chemical Formula: C6470H10012N1726O2013S42

Molecular Weight: 148 kilodaltons

Aspirin

Chemical Formula: C9H8O4

Molecular Weight: 180 daltons

Biologic Drug

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Biologics Are More Difficult to Produce Than Small-Molecule Drugs

Clone gene into a vector

Transfect into a vector cell, screen, subclone, and produce “master and working cell

banks”

Cell culture expansion up to commercial scale

Purify protein in an

advanced multistep process

Analyze the protein for quality and establish desired quality attributes

Final formulation analysis and packing of protein suitable for transport, storage, and

final use

Produced product analyzed

Final formulation is analyzed and packaged for distribution

Chemical synthesis via multiple chemical processes

1. Strober B, et al. J Am Acad Dermatol. 2012;66(2):317-322; 2. Kuhlmann M, Covic A. Nephrol Dial Transplant. 2006;21(suppl 5):v4-v8.

Small-Molecule Production Steps1 Biologic Production Steps2

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Factors That Impact Immunogenic Potential

Glycoforms

Glycoforms are glycoprotein molecules with the same

protein component, but different ensembles of sugar chains.

Rudd, P. M., et al. (1997) The glycosylation of the complement regulatory

protein, human erythrocytes CD59. J. Biol. Chem. 272:7229.

Schellekens H. Nat Rev Drug Discov. 2002;1(6):457-462.

Structural Properties

Sequence variation (human; bacterial)

Glycosylation

Immunogenic Potential

Other Factors

Contaminants and impurities (from initial production

or downstream processing)

Formulation

Route of application

Dose

Length of treatment

Assay technologies

Patient characteristics

Unknown factors

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Oncology Biologics: Patent Expiration Dates

* Patent expirations are listed as provided in reference 2. 1.Datamonitor. Biosimilars: Market Entry Strategies. HC00149-003; Publication Date: 20 December 2011. 2.Gal A, et al. In: Biosimilar: Quo Vadis-A Snapshot of the Biosimilar Industry Halfway Through Its

Formation. New York: Bernstein Research; June 2011.

Epoetin alfa Filgrastim

Pegfilgrastim Adalimumab Cetuximab Rituximab

Bevacizumab Darbepoetin

Infliximab Trastuzumab

United States

Europe Rituximab Cetuximab Infliximab

Trastuzumab Darbepoetin

Adalimumab Bevacizumab Pegfilgrastim

Many Biologic Patents Will Expire Soon1,2*; Over $90B of Biologic Products Will Be Off Patent by 20171

2013 2014 2015 2016 2017+

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

The Cost Burden Associated With Biologics: US Example

Drug Expenditures for Top 20 Oncology Drugs in US Outpatient Clinics in 20101,2

Drug Type Total ($M)

Bevacizumab Biologic 1,884

Rituximab Biologic 1,466

Trastuzumab Biologic 931

Docetaxel Nonbiologic 688

Pemetrexed Nonbiologic 579

Oxaliplatin Nonbiologic 508

Gemcitabine Nonbiologic 463

Cetuximab Biologic 329

Bortezomib Nonbiologic 327

Leuprolide Nonbiologic 220

Paclitaxel-albumin Nonbiologic 212

Bendamustine Nonbiologic 208

Azacitidine Nonbiologic 148

Liposomal doxorubicin Nonbiologic 130

Decitabine Nonbiologic 92

Topotecan Nonbiologic 86

Fulvestrant Nonbiologic 81

Panitumumab Biologic 70

Ixabepilone Nonbiologic 60

Temsirolimus Nonbiologic 48

$3.848,21 $4.679,36

Biologics ($M) Nonbiologics ($M)

55% 45%

1.Zelenetz AD, et al. J Natl Compr Canc Netw. 2011;9(suppl 4):S1-S22. 2.Doloresco F, et al. Am J Health Syst Pharm. 2011;68(10):921-932.

Top 3 US Expenditures Were Biologics

Biologics accounted for more than half (55%) of the total expenditures for the top 20 oncology

drugs in outpatient clinics in 20101,2

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Biosimilars Have the Potential to Lower Healthcare Costs

Source Estimated Biosimilar Savings

CBO1 Savings of $25 billion during 2009-2018 in US following implementation of bill S. 1695

PCMA2 Medicare Part B: $14 billion over 10 years

EGA3 €1.6 billion, assuming a 20% discount for just 6 biologic drugs

IGES Institut GmbH4 €11.8 to €33.4 billion between 2007-2020 in 8 EU countries

Range of Estimates on the Cost Savings That Could Be Realized by Healthcare Systems With The Availability of Biosimilars

CBO, Congressional Budget Office; EGA, European Generic Medicines Association; PCMA, Pharmaceutical Care Management Association. 1. Congressional Budget Office. S. 1695 - Biologics Price Competition and Innovation Act of 2007. June 25, 2008; 2. Engel and Novitt, LLP. Report to PCMA on Potential Medicare Savings. January 2, 2007; 3. European Generic Medicines Association. The Future of Pharmaceuticals: Generic Medicines Enhancing Pharmaceutical Competition and Ensuring Healthcare Sustainability. Brussels, Belgium: EGA; 2007; 4. Haustein R, et al. GaBI J. 2012;1(3-4):120-126.

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Comparative Clinical Trials Are Required to Prove Biosimilarity

Biosimilarity1,2

Requires demonstration of bioequivalence and efficacy and safety using either equivalence or noninferiority

Bioequivalence3 Pertains to pharmacokinetic testing, most often Cmax and AUC

Equivalence4 Statistical testing showing new product is no better and no worse than a reference product

Noninferiority4 Statistical testing showing new product is at least as good as a reference product

Impact on sample size5 Sample size required for equivalence > sample size required for noninferiority

1. FDA. Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product [draft guidance]. Rockville, MD: FDA; 2012. 2. EMA. Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Non-Clinical and Clinical Issues.

London, UK: EMA; 2006. 3. FDA. Guidance for Industry: Statistical Approaches to Establishing Bioequivalence. Rockville, MD: FDA; 2001. 4. ICH. ICH Harmonised Tripartite Guideline: Statistical Principles for Clinical Trials E9. Brussels, Belgium: ICH; 1998. 5. Da Silva et al. Biol Blood Marrow Transplant. 2008;15(1, suppl):120-127.

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Biosimilar Regulatory Guidance

1. FDA Web site. How Drugs are Developed and Approved. Last updated January 3, 2013 . http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/default.htm. Accessed April 30, 2013.

2. EMA. www.ema.europa.eu/ema. Accessed April 30, 2013. 3. WHO. Expert Committee on Biological Standardization: Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs).

Geneva, Switzerland; 2009.

FDA1 EMA2 WHO3

Length of immunogenicity study and comparative vs noncomparative phase

(Extent and timing of program will vary)

(Product dependent; 1-year follow-up

data required pre-license for chronic

administration)

(Length dependent on duration of therapy and expected antibody

development time)

Position on interchangeability

(Draft guidelines: produce same clinical effect

with no safety, efficacy difference on switching)

Not under EMA jurisdiction

Request for pharmacovigilance study

Extrapolation of indication

(Extrapolation possible if sensitive clinical test model, similar MOA, and similar safety and immunogenicity issues in different population)

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Biosimilar Regulatory Guidance

PD, pharmacodynamics; PK, pharmacokinetics. 1. EMA, Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1) ; EMA/CHMP/BWP/247713/2012. Released 22 May 2014. Accessed 7/7/2017. 2. Schneider CK, et al. Nat Biotechnol 2012;30:1179-1185. 3. McCamish M. Presented at EMA Workshop on Biosimilars; London; October 2013. 4. Berghout A. Biologicals. 2011;39:293-296. 5. US Food and Drug Administration. Abbreviated New Drug Applications (ANDA): Generics. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/. Accessed 3/7/2017.

Standard Biologics1,2

Nonclinical

Clinical pharmacology

PK/PD

Analytical

Clinical studies

Analytical

Bio-

equivalence in Healthy Volunteers

Small Molecule Generics1,4

Biosimilars1-3

Nonclinical

Comparative clinical

pharmacology PK/PD

Analytical

Comparative

Clinical studies

Confirm safety profile and efficacy in a disease population (dose ranging not necessary)

The level of evidence required for biosimilar approval is different from originator biologics

Tota

lity

of

evid

ence

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Biosimilar Regulatory Guidance

The scope and number of clinical trials required for biosimilar approval is determined on a case-by-case basis

• Depends on residual uncertainty after analytical characterization and human PK assessment

When a biosimilar is approved, there is an expectation that there will be no clinically meaningful differences in safety, immunogenicity, and/or efficacy

Since biosimilars are not identical to their reference products, phase 1 and phase 3 comparative clinical trials are generally required

The goal of the clinical program is NOT to independently reestablish safety and effectiveness, but to demonstrate biosimilarity

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Biosimilar Regulatory Guidance

Superiority: Experimental intervention is superior to the control intervention

• Not useful when evaluating biosimilars

Noninferiority: Experimental intervention is non-inferior to the control intervention

• May be adequate for the evaluation of immunogenicity or other safety outcomes

Equivalence: Experimental intervention and the control intervention are equivalent

• More commonly used as demonstrating that the biosimilar is equivalent to the reference product is the goal

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Biosimilars: Balancing Risk and Benefit in the Approval Process

Zelenetz AD, Ahmed I, Braud EL, et al. J Natl Compr Canc Netw. 2011;9(Suppl 4):S1-S22.

Biosimilar Development and Regulatory

Approval Process

Approval Process Requires Too Little

Amount of Data

Benefits: • Lower development costs • Greater pharmacoeconomic benefit over innovator

product Risks:

• Lower HCP confidence in biosimilar product • Less acceptance and uptake of biosimilar? • Greater safety concerns

Benefits: • Greater HCP confidence in biosimilar product • Greater acceptance and uptake of biosimilar • Fewer safety concerns

Risks: • Higher development costs • Lower pharmacoeconomic benefit over innovator

Approval Process Requires Too Large

Amount of Data

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

What EMA Guideline on Biosimilar Antibodies Says?

• The guiding principle is to demonstrate similar efficacy and safety compared to the reference medicinal product

• Therefore, in general the most sensitive patient population and clinical endpoint is preferred

• Comparability should be demonstrated in scientifically appropriately sensitive clinical models and study conditions

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Key Differences in Requirement and Study Design for Biosimilar and Innovator Clinical Trials

Biosimilar Innovator

Patient population Sensitive and homogeneous patient population

Any/Sensitive population

Clinical design Comparative versus innovator (equivalence studies)

Superiority vs standard of care

Study endpoints Sensitive

Clinically validated PD markers; ORR, pCR

Clinical outcomes data (OS, PFS) or accepted/established

surrogates

Safety Similar safety profile to innovator

Acceptable risk/benefit profile vs standard of care

Immunogenicity (tested in most sensitive population)

Similar immunogenicity profile to innovator

Acceptable risk/benefit profile vs standard of care

Extrapolation Possible if justified Not allowed

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Key Considerations for Biosimilar Trials

Topic Metastatic Population Neoadjuvant/Adjuvant population

PK Affected by patient’s health status &

tumour burden

Homogeneous population can be selected Variability is also observed

Healthy Volunteers

PD Clinically validated PD marker not available

Clinical efficacy/safety

• Difficult to select homogeneous group • Need to control and stratify for multiple factors (eg, prior use of chemotherapy, performance status). • Population with heterogeneous characteristics affecting final clinical outcome.

• Populations less likely to be confounded by baseline characteristics and external factors • Sub-group of patients with higher responses could be identified (e.g. hormone receptor negative patients)

Immunogenicity Immune system affected by performance

status and concomitant chemotherapies received

Immune system impaired during

chemotherapy cycles, but likely to recover to normal status thereafter

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Efficacy of Biosimilars: Sensitive endpoints

• EMA guidelines identify ORR as a sufficiently sensitive endpoint for clinical trials of biosimilar antibodies

• Very often ORR does not correlate to survival

• Survival endpoints such as overall survival or progression-free survival may provide superior data, but may take too long for a biosimilar antibody trial

• Which endpoint should be used in a biosimilar antibody trial remains a controversial issue

– Current clinical trials of biosimilar trastuzumab use response and safety as primary endpoints

– The goal of biosimilar trials is to demonstrate comparability, which ORR allows, not necessarily efficacy

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Response Rate: Pros and Cons

PROS CONS

Indicator of drug activity when it is present

Subject to measurement error and bias

Samples sizes typically smaller than with time-to-event endpoints

RR does not necessarily indicate improved patient outcome

A faster method of assessing drug activity than survival

Association with overall survival questionable

Is ORR sufficiently sensitive endpoint for approval of biosimilar antibodies?

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Traceability of Biologic Products

• Clear identification of the product administered is essential to pharmacovigilance, traceability, and assessment of causality

• Emphasis on prescribing by brand name

– Section 4.4 of MabThera SmPC: “In order to improve the traceability of biological medicinal products, the trade name of the administered product should be clearly recorded (or stated) in the patient file”1

• Ensure manufacturers can deliver drug supply to prevent product switching in patients – diminished ability to trace long-term product safety2 and added cost-burden for national health system3

1. MabThera SmPC 2013. Available at www.medicines.org.uk/emc. Accessed 15 May 2013.

2. AFSSAP Expert Report July 2011. Available at: http://www.afssaps.fr/Infos-de-securite/Points-d-information/Medicaments-

biosimilaires-Point-d-information. Accessed 15 May 2013.

3. http://www.gabionline.net/Pharma-News/Biosimilars-and-cancer-drug-shortages-in-Europe. Accessed 15 May 2013. 17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Accurate Identification of the Drug Given to a Patient Is Essential

• “…in order to support pharmacovigilance monitoring, the specific medicinal product given to the patient should be clearly identified.”

• Physician should be well advised to always document exactly which biological is used for an individual patient. In the Adverse Drug Reaction (ADR) report ….INN, brand name, manufacturer, lot number, country of origin should be included to ensure a proper root cause analysis

EMA Guideline on Similar Biological Medicinal Products CHMP/437/04, October 2005; Ehmann, F., Schneider K. HPE 2011;56:32-35. 17th ESO-E

SMO Maste

rclass

in C

linica

l Onco

logy

Postmarketing Surveillance

• Post approval, biosimilars must undergo at least one year of post-marketing surveillance to detect incidence of immunogenicity and other adverse events

• This includes detailed risk management plans that should be followed by both physicians and pharmacists

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Extrapolation of Indications

• Risk assessment of immunogenicity requires

– Multidisciplinary approach

– Related pivotal aspects that must be considered are

• Rate of occurrence and clinical consequences of unwanted immunogenicity

• If they can be prevented

• If they can be measured

• If they can be treated; is there a therapeutic alternative?

• In oncology setting it can be challenging

– How to distinguish loss of clinical response due to natural progression (unavoidable) from neutralization by anti-mAb antibody response (potentially treatable)

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Automatic Substitution

• Automatic substitution = substitution by a pharmacist without the physician's consent

• Generic drugs may be automatically substituted for reference drugs because they are the same

• Biosimilars are similar to the originator drugs, not identical, and there is currently no scientific basis to substitute different products

• Regulatory decisions on substitution are left to individual countries

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

What Every Oncologist Should Know

• MYTH 1: Cheaper = potentially less safe

Biosimilars are expected to be priced approximately 20% to 30% lower than their reference biologic, which has the potential to translate into substantial cost savings to the health care system. However, the reduced cost of these agents does not automatically imply a reduction in safety standards.

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

• MYTH 2: Confirmatory trials are too small to detect clinically meaningful differences

A properly powered clinical trial to determine absolute equivalence between a biosimilar and its reference biologic would require thousands or even tens of thousands of patients, substantially larger than the size of the confirmatory trials required by the FDA for approval of a biosimilar. However, such trials are not necessary. A biosimilar agent is an“highly similar to the reference product notwithstanding minor differences in clinically inactive components” with “no clinically meaningful differences” in “safety, purity, and potency”

What Every Oncologist Should Know

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

• MYTH 3: Pharmacovigilance will be poor without different nonproprietary names

• Nonproprietary names, (e.g., filgrastim) serve to indicate the active ingredient in a brand name product, and are designed to reduce confusion regarding the therapeutic class to which a drug belongs. There is currently an ongoing debate regarding the nonproprietary naming convention to be applied to biosimilars, with some arguing that biosimilars for a given reference biologic should share the same nonproprietary name as the reference drug, as is the case with generics, while others argue that each biosimilar should be issued a distinct nonproprietary identifier.

What Every Oncologist Should Know

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

• MYTH 4: Extrapolation is dangerous without clinical trials for each indication

• Some clinicians have expressed concern that because the mechanisms of action of most biologic agents are not fully understood. However, if a confirmatory trial is conducted in the most sensitive or representative patient population, and solid comprehensive evidence from structural and functional assays is provided demonstrating a high degree of similarity between the biosimilar and reference biologic, it is very unlikely that clinically meaningful differences would be detected in subsequent trials to confirm additional indications of the reference agent

What Every Oncologist Should Know

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Conclusions

• The aim of clinical trials with biosimilars is to show equivalence and not patient benefit

• If biosimilars are approved, several challenging issues will need to be addressed such as maintaining appropriate pharmaco-vigilance, extrapolating across indications, and automatic substitution and switching

• Slight alteration in manufacturing of biologics can lead to clinically relevant changes, particularly concerning potency.

• With many biologics going off patent in the near future, an opportunity exists to expand access through the availability of biosimilars. They can be the future of sustainable cancer care

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Drug repositioning

• Drug repositioning (also known as drug repurposing, re-profiling, re-tasking) is the application of known drugs and compounds to treat new indications (i.e., new diseases).

• A significant advantage of drug repositioning over traditional drug development is that since the repositioned drug has already passed a significant number of toxicity and other tests, its safety is known and the risk of failure for reasons of adverse toxicology are reduced. More than 90% of drugs fail during development

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Drug repositioning

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Drug repositioning

• Using drug repositioning, pharmaceutical companies have achieved a number of successes; for example, Pfizer's Sildenafil developed to treat pulmonary arterial hypertension and repositioned for erectile dysfunction

• Celgene's thalidomide developed to treat pregnancy associated nausea and the repositioned as antiangiogenic for MM and for severe erythema nodosum leprosum.

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Drug repositioning

• Plerixafor, initially developed as an HIV drug to block viral entry in the cell via the chemokine co-receptor CXCR4, failed in its initial medical indication. Nevertheless, it was noticed that the drug induced peripheral blood leukocytosis within which peripheral blood CD34 hematopoietic stem cells were found. On basis of this observation, the drug has been re-purposed as a stem cell mobilizing drug

• Another example of drug repurposing is that of gabapentin, and its chemical cousin pregabalin. Originally developed as anti-epileptics, they have found more use treating anxiety disorders and neuropathic pain than as seizure medications.

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Drug repositioning

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Drug repositioning

• Drug repurposing programs in oncology have been limited thus far, and have provided very few suc- cesses.

• Academic and independently driven preclinical and clinical research programs should be promoted both nationally and internationally.

• For these programs to be successful and ulti- mately bring benefit to patients with cancer, the design and the quality of repurposing trials will need to be optimal.

• Broad communication of the results of well-performed repurposing trials will also be necessary to ensure they become practice-changing.

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology

Giuseppe Curigliano MD, PhD giuseppe.curigliano@ieo.it 17th ESO-E

SMO Maste

rclass

in C

linica

l Onco

logy

Thank you

17th ESO-ESMO M

astercl

ass in

Clin

ical O

ncology