Originators and Princeps: How to face Biosimilars and Generics

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Originators OR Princeps --------------------

How to face Biosimilars and Generics

Joseph Pategou

International Strategy and Influence

[email protected]

23/05/2016 Originators and Princeps - How to face Biosimilars and Generics –Joseph Pategou

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SUMMARY

I. How to face GENERICS

II. How to face BIOSIMILARS

Conclusion

Information about the Author

Appendix

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How to face Generics

Originators and Princeps - How to face Biosimilars and Generics –Joseph Pategou

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Context

This wave of patent loss has allowed the development of new generic drugs. A

Global analysis finds that the market earned revenues is $123.85 billion in 2010 and

will reach $231.00 billion in 2017 at a compound annual growth rate of 9.29 % from

2011-2018.

The entry of generics has had huge impact in particular on the price of medecine

or the turnover of some pharmaceuticals companies. For example, in Germany the

prices of generic drugs are on average 71% lower than those of their originators and

in France it’s about 75% to 80%. To face this upheaval of the landscape of the

medicine, producers of originators have set up various strategies.

For our benchmark we observe action of 11 companies from 2000 to 2015

(See table 14)


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Context


Company Product

Glaxosmithkline Augmentin, Paxil, Amoxicilline

Lilly Prozac

Hoechst Cardizem

Servier Périndopril

Merck & Co Claritin

Fournier Lipanthyl

Astrazeneca oméprazole

Merck-Lipha Glucophage

MSD Inegy, Zocor

Pfizer Gabapentine

Bristoll Myers Squibb Buspirone

Teva Simvastatine

Table 14: Sample of the benchmark in US and EU

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How to face Generics


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How to face Generics: Price


The price reduction of the originators at the level of the price of the generic medicines

can allow to keep the advantage acquired by the brand and to preserve a part of his

market. This policy is only relevant when demand is price sensitive.

The impact of the strategies of companies differs according to market conditions. We

thus notice a particular evolution of markets upon the arrival of the generic medicines.

A originators would have many generics when his sales and price are high.

The evolution of the price of the originators depends on the sensitivity of demand

to the price of the product.

The falling price of the originators or the production of generic by the producer of

originators limits the penetration of generic competitors on the market.

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How to face Generics: Patent


Early in the life cycle of the drug, patent protection is the major tool to counter

the entry of generic. To increase its protection, the laboratory puts down, after

the discovery of the molecule, a whole series of patents: patent on the

molecule, on indications etc.

The multiplicities of patents, as well as their spreading in time, allow the

laboratory to make more complex the identification of the valid patents by the

potential producers of generics and to lengthen the period of exclusivity

covered by patents. GlaxoSmithKline (GSK), for example, filed four new

patents for Augmentin in 2000 in the United States, two years before the

expiration of the first patents.

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How to face Generics: Legal Action


The legal battles between producers of originators and manufacturers of

generics are the most media. The first ones accused the second of violating

unexpired patents or dispute the bio-equivalence claimed by generic

companies.

The action of justice for violation of the patent has for consequence the

suspension of the marketing of the generics medicines. It allows big

laboratories to win some invaluable weeks of exclusivity on the market. For

example: GSK has filed several lawsuits for violation of patents of Paxil in the

US and Lilly sued generic makers of Prozac for the same reasons.

Source: Les laboratoires pharmaceutiques face à l’arrivée des génériques : quelles stratégies

pour quels effets ?- Bulletin d’information en économie de la santé-n° 84 - Octobre 2004

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How to face Generics: Cooperation


Some pharmaceutical companies have reached financial agreements with

producers of generic to postpone competitors launch on the market.

For the European Commission, Servier had work with 5 generics

companies (Niche/Unichem, Matrix ( Mylan), Teva, Krka and Lupin.) to slow

down the entrance on the market of generic versions of his medicine, marketed

under the name of Coversyl, to handle the high blood pressure and the cardiac

insufficiency. The European Commission heavily sanctioned the laboratory

Servier with a 331 million euro fine to have hindered the launch on the market

of generic versions of its product

Source: http://www.bloomberg.com/news/articles/2014-07-09/servier-to-teva-fined-582-2-

million-on-generic-delays

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How to face Generics: Production


Creation of new formulations and new methods of administration possibly

patentable. The laboratory intensely promotes these innovations before patent expiry of

the original formulation, so that they supplant in the prescriptions or the consumer

habits (eg dispersible Prozac, Prozac Weekly)

They developed new dosages containing for example less active ingredient for a

similar efficiency (Lipanthyl® 160 mg was placed on the market to replace the

Lipanthyl® micronized 200 mg).

They make associations of a molecule with another one. For example, in Germany

Inegy® combines the active ingredients of Zocor ® (simvastatin) and Ezetrol®

(ezetimibe).

They developed new products, very close to the initial product and could be

replaced. For example: In the case of the oméprazole, the isomeric molecule was

launched on the market in the United States two years before the arrival of the generic

medicines and allowed AstraZeneca to keep about three quarters of the market which

he had in this indication.

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How to face Generics: Market Saturation


The laboratory can produce itself the generic medicine of one of its

originators; like that the company will have many products on the

market and would increase its opportunity to sell one product of the

portfolio.

For example, Merck-Lipha continues to market Glucophage

whereas Merck Generics launched on the market a Metformine Merck.

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How to face Generics: Prescription


The new European regulations promote this strategy by granting

one year additional exclusivity for products that laboratories decided to

switch to OTC . Pharmaceutical laboratory make the drug available

without a prescription and bet on attachment to the brand.

The Claritin (loratadine ) medicine of the laboratory MSD became

OTC in the United States in November, 2002. Generic version entered

on the market in the end of December, 2002.

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How to face BIOSIMILARS


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Context

The EMA has approved 20 biosimilars within the product classes of human growth hormone, granulocyte

colony-stimulating factor, erythtropoesis stimulating agent, insulin and tumour necrosis factor (TNF)-inhibitor,

for use in the EU . The first biosimilar launch in the EU (Omnitrope/Somatropin) occurred in Germany in 2006.

This introduction of the biosimilars on the market has many impacts. For example, biosimilars of

filgastrim are used more than the reference product (Neupogen), allowing more patients to benefit at lower

costs. The savings achieved through the use of filgrastim biosimilar is estimated at € 318M since 2009.

In this part we will study how the laboratory Amgen, producer of Neupogen responds to the arrival of

biosimilars.

Amgen is an American company world leader in medical biotechnology industry. It has over 18 000

employees for a turnover of $ 20 billion in 2014 and his headquarter is in California.

Amgen has 14 products on different type’s diseases and Neupogen is one of them.

The first commercialization of Neupogen in Europe was in 1991 with the collaboration of Roche . In

2008, this blockbuster represented 1,4 billion dollars and according to Symphony Health Solutions, Neupogen

had approximately $1,2 billion in sales in calendar year 2014.

The time of total exclusivity enjoyed by Amgen for the Neupogen depend on the country


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How to face Biosimilars: Prescription


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How to face Biosimilars: Price


When the filgrastim biosimilars enter into the market they provide an

average discount of 10.8% in 2008 and 35.0% in 2009. Amgen needs to

adapt his price to face this situation. We clearly see that we have a

difference in terms of price between biosimilar and originators. Amgen has

tried to adapt his price to remain competitive, but we still have differences.

(See graph 23). The price of the two types of drugs decrease over time,

biosimilar and originators follow each other.

Source:

http://www.codage.ext.cnamts.fr/codif/bdm_it//fiche/index_fic_medisoc.php?p_code_cip=3400935395214&p_site=ameli

http://www.codage.ext.cnamts.fr/codif/bdm_it//fiche/index_fic_medisoc.php?p_code_cip=3400935395214&p_site=ameli

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How to face Biosimilars: Patent


Over time Amgen has developed 5 indications for his product

(incremental patenting).

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How to face Biosimilars: Legal Action


Novartis' Sandoz is the first drug maker to win U.S. approval of a biosimilar product. But the

United States court of appeals for the federal circuit gave an injunction against Sandoz, preventing

that company from marketing, selling, offering for sale, or importing into the United States its

FDA-approved ZARXIO® biosimilar product until the court resolves the appeal . This give more

time to Amgen to sell his product.

Amgen based his action on the fact that the pre-litigation information-exchange provisions of

the Biologics Price Competition and Innovation Act of 2009 (BPCIA) are mandatory and for

Sandoz this is optional. The BPCIA states that a biosimilar applicant "shall provide" a copy of its

FDA application and manufacturing information to the Reference Product Sponsor (RPS) here,

Amgen. The statute further states that in the event that a biosimilar applicant fails to provide its

application and manufacturing information, the RPS may file a declaratory judgment action

against the applicant .

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How to face Biosimilars: Cooperation


The company’s CEO Kevin Sharer stated in January 2011 that in order to drive growth, the

company was going to consider entering the biosimilars sector but “in a controlled way,” (Beasley,

2011).

In December 2011, Amgen announced it had signed a deal with Watson to develop and

commercialize a number of oncology biosimilar monoclonal antibodies (MAbs) . Under the

agreement, Amgen will be primarily responsible for developing, manufacturing and initially

commercializing the products, while Watson will put in up to $400m in co-development costs and

will share product development risks. Biosimilars from the collaboration are expected to be sold

jointly by both companies.

Amgen has secured a clause which prevents the collaboration from making biosimilar

versions of its drugs including Enbrel (etancercept), Aranesp (darbepoetin alfa) and Epogen

(epoetin alfa).

This deal gives the opportunity to Amgen to enter the biosimilars arena, to develop his

know how and to know more how his can protect his product, Neupogen.

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How to face Biosimilars: Production


Neulasta (pegfilgrastim) can be considered as a new version of Neupogen.

They are both made of a natural protein known as granulocyte-colony

stimulating factor (or "G-CSF"). Pegfilgrastim (Neulasta) has a polyethylene

glycol, "PEG," unit added to it, which makes the molecule larger, so that it

stays in your system longer than filgrastim (Neupogen). Two forms of G-CSF

are approved for use in pediatric cancer patients.

The needs for fewer injections with Neulasta (pegfilgrastim) improve quality

of life for pediatric oncology patients and their families .

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How to face Biosimilars: New Market


Amgen bought the rights of Neupogen and Neulasta in more than 100

emerging markets where the drugs were sold by Roche .

Amgen believes it can drive growth of Neupogen (filgrastim) and Neulasta

(pegfilgrastim) more effectively in the Roche territories, which cover the

world's emerging economies including Eastern Europe, Latin America, Asia,

the Middle East and Africa.

For Robert Bradway the chief executive of Amgen "This agreement will

enable Amgen to reach more patients around the world with two of its

innovative medicines."

All this 6 levers help Amgen to maintain a high level of sell for his product

Neupogen: 1.2 billion in 2014 dollars.

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How to face Biosimilars: New Market


Amgen bought the rights of Neupogen and Neulasta in more than 100

emerging markets where the drugs were sold by Roche .

Amgen believes it can drive growth of Neupogen (filgrastim) and Neulasta

(pegfilgrastim) more effectively in the Roche territories, which cover the

world's emerging economies including Eastern Europe, Latin America, Asia,

the Middle East and Africa.

For Robert Bradway the chief executive of Amgen "This agreement will

enable Amgen to reach more patients around the world with two of its

innovative medicines."

All this 6 levers help Amgen to maintain a high level of sell for his product

Neupogen: 1.2 billion in 2014 dollars.

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How to face Biosimilars: Environmental Strategy

3 Actions:

Promote the obligation of the four-letter code (BQ) at the end of the

name of Biosimilars

Promote for the Biosimilar a different Summary of Product

Characteristics (SmPC) from the Generics and Originators

Promote the substitution of Biosimilars by physicians

All this will contribute to highlight that biosimilars unlike generics

are not identical to originators, but different products

BQ: Biological QualifierSource: Interview


2 Actions:

Create more adhesion of patients and healthcare professionals to their

drugs (adhesion to the brand)

Bring more services to patients and healthcare professionals on their drugs

(For example monitoring)

Example: Amgen’s Evaluation of personalized patient counseling for

Enbrel

Phase IV trial with 300 patients with RA

Patient adherence and persistence to therapy in chronic disease

Justify a premium price for Enbrel over Biosimilars

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How to face Biosimilars: Brand Strategy

Source: InterviewRA: Rheumatoid Arthritis


Price

Patent

Legal Action

Cooperation

Product

Prescription

Market Saturation

New Market

EnvironmentalStrategy

Brand Strategy

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Conclusion

10 Levers

1

4

3

2

8

7

6

5

10

9


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Conclusion

Regulatory issues on the development of Biosimilars – Joseph Pategou

Source: Interview

No Single but Combination of Strategy

No Global but Glocal Strategy

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Information about the author

I am fascinated by healthcare and the experience of many

companies to develop new types of drug with the aim of saving

lives around the world.

Main topics of passion in the healthcare:

- Strategy

- Digital

- Innovation

- Biosimilars

If you want to know more, please contact me:

[email protected]

M. Joseph Pategou


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THANK YOU FOR YOUR ATTENTION


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APPENDIX


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COMPARISON OF DIFFERENCE AND COMMON POINTS BETWEEN

BIOSIMILARS AND GENERICS-STRUCTURE

KEY POINTS BIOSIMILARS Generics

NatureDrug extracted from a biological

environmentChemical drug

Molecular size Up to 270,000 Da 100 to 200 Da

Development Comparative studies Bioequivalence studies

Duration of development 5-7 years(500 patients) 2-3 years (20-50 patients)

Cost of the development 200-300 million dollars 2-4 million dollars


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REFERENCE

1. http://www.sante.gouv.fr/qu-est-ce-qu-un-generique.html

2. Where the opportunities are and what role will they play? EGA Lisbon 2011-IMS

3. http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/document_listing/document_listing_000318.jsp

4. http://www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe

5. http://www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe

6. Shaping the biosimilars opportunity-december 2011

7. http://www.sante.gouv.fr/qu-est-ce-qu-un-generique.html

8. Rapport 2012 sur les médicaments génériques-Mutualité Française

9. EMA Procedural advice for users of the centralized procedure for generic/hybrid applications

10. Lessons learned from the review of the labelling of 5 centrally authorised pandemic vaccines- 10 February 2014 EMA

11. Rapport 2012 sur les médicaments génériques- Mutualité Française

12. http://gabionline.net/Biosimilars/General/Germany-wants-to-increase-biosimilars-penetration

13. http://ec.europa.eu/health/authorisation-procedures_en.htm

14. Guideline on the investigation of bioequivalence- London, 20 January 2010- European Medicines Agency

15. http://www.australianprescriber.com/magazine/26/4/article/712.pdf

16. Directive 2001/83/EC, as amended by Directive 2003/63/EC and Directive 2004/27/EC

17. Biosimilars Marketing Authorisation status as of January 2013: 22 Marketing Authorisation Applications

18. http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/document_listing/document_listing_000318.jsp

19. Individual case safety report: Article 28 of Commission Implementing Regulation (EU) No 520/2012 of 19 June 2012

20. Biological Qualifier An INN Proposal-July 2014- World Health Organization, Geneva

21. http://www.gabionline.net/Biosimilars/Research/Improved-labelling-sought-for-biosimilar-acceptance

22. EC consensus paper 2013- What you need to know about Biosimilar Medicines

23. European Commission consensus paper 2013 : What you need to know about biosimilar medicines

24. http://gabionline.net/Biosimilars/General/Germany-wants-to-increase-biosimilars-penetration

25. http://gabionline.net/Biosimilars/Research/Extrapolation-for-biosimilars

26. Directive 2001/83/CE du parlement européen et du Conseil du 6 novembre 2001 instituant un code communautaire relatif aux

médicaments à usage humain

27. Where the opportunities are and what role will they play? EGA Lisbon 2011-IMS

28. http://healthcare.blogs.ihs.com/2012/01/06/generic-drug-price-trends-france-germany-italy-spain-uk/


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REFERENCE


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REFERENCE


Originators and Princeps: How to face Biosimilars and Generics

Health & Medicine

Transcript of Originators and Princeps: How to face Biosimilars and Generics