Economic Analysis of Availability of Follow-on Protein Products. Appendix B: Overview of Top Ten Biologic Categories B-1

07/27/2009

Table B-1: Overview of Top Ten Biologic Categories (in descending order according to annual sales)

 Biologic Category   2006 Annual Sales within Category ($B)1   Growth Rate in Sales from 2005 to 20061   Indication(s)   Size of Affected Population   US/EU Approved FoPP(s)   Estimated Influence of FoPPs 7   Market Factors   Pros   Cons 
 Erythropoietins (EPO)   $11.94    6.7%    Anemia1    800,000 4   Yes2,6    1   Recent negative publicity regarding cardiovascular safety of EPO drugs10   Highest annual sales Large affected population EU approved FoPP Greatest estimated influence of FoPP BLA pathway   Smaller growth rate in sales Concerns about cardiovascular safety in some patients 
 Major cancer monoclonal antibodies (MAbs)   $10.62    56.8%    Various forms of cancer (e.g., metastatic colorectal cancer, non-Hodgkin's lymphoma, certain forms of breast cancer)1,3   Not available   No   4   Recombinant MAbs are expected to be insulated from generic competition through 2018 given patent protections9,11   Second highest annual sales Largest growth rate in sales High estimated influence of FoPP BLA pathway   Potential patent protection until 2018 
 Anti-tumor necrosis factor (anti-TNF) agents   $10.28    24.8%    Rheumatoid arthritis, psoriasis, and other conditions (e.g., Crohn's disease, ulcerative colitis) 1,3   Not available   No   Not ranked   Some anti-TNFs use MAb technology and therefore will have some of the same patent issues as Mabs11   Third highest annual sales Large growth rate in sales BLA pathway   Non-biologic treatments availableRelatively newer biologic category Some anti-TNFs have potential patent protection until 2018 
 Insulin and insulin analogs   $8.97    24.4%    Diabetes1    14,600,000 4   No   2   Market challenges given domination by key companies (e.g., Lilly), complexity of advanced delivery systems, and erosion of the market by insulin analogs, which are patent-protected until 20132   High annual sales Largest reported affected population Large growth rate in sales High estimated influence of FoPP   Second generation and analog products have eroded the market Monopoly held by very few large companies NDA pathway 
 Recombinant coagulation factors   $4.71    17.0%    Certain bleeding disorders, including hemophilia1   18,000 (hemophilia)5    No    5    Clinical trials are required for approval of each new product12    High annual sales Moderate growth rate in sales BLA pathway    Clinical trials required for the approval of every product Small affected population Low estimated influence of FoPP  
Interferon beta    $4.40    14.4%    Multiple sclerosis1    340,000 4    No    3 (Interferons as a group)    Patent situation for interferon beta products is regarded as complex; new dosing schedules and delivery approaches are expected to increase competition2,8    Large affected population Moderate growth rate in sales High estimated influence of FoPP BLA pathway    Lower annual sales Non-biologic treatments available 
 Granulocyte-colony stimulating factor (G-CSF)    $4.36    11.4%    Neutropenia; congenital or acquired (e.g., as a result of chemotherapy)1,2    Not available    Yes14,15,16,17,18,19    Not ranked    Longer acting form of G-CSF (Neulasta) has majority of US market share and patent is not expected to expire until 2015; first generation Neupogen has lower sales and market share2, 8    Moderate growth rate in sales BLA pathway    Market erosion by second generation pegylated G-CSF Lower annual sales  
 Human growth hormone (hGH)    $2.47    6.9%    Growth deficiency/ failure1    12,000 4    Yes2    1    There are no second generation hGH products2    FoPP Omnitrope already approved for use in the US No second generation products to erode the market Highest estimated influence of FoPP    Small affected population Lower annual sales Small growth rate in sales NDA pathway  
 Interferon alpha $2.26 6.9% Various conditions (e.g., chronic hepatitis B and C, renal cell carcinoma, malignant melanoma, myeloma, certain leukemias)1 Not available No 3 (Interferons as a group) One FoPP, Biopartners' Alpheon,received a negative opinion from EMEA
based on concerns over comparability with the reference product; second generation pegylated products, which are administered less frequently, have eroded the market for first generation interferon alpha2; pegylated interferon alpha products have a significant clinical advantage over non-pegylated products 13
High estimated influence of FoPP BLA pathway Second smallest annual sales Shrinking growth rate in sales Smaller affected population
Enzyme replacement $1.71 27.5% Various conditions (e.g., Fabry disease, Gaucher disease, Pompe disease)2 Not available No 6 None reported Large growth rate in sales BLA pathway Smallest annual sales Comprises several smaller treatment indications Small affected population
Low estimated influence of FoPP

Sources

1:Top 20 biologics. Barcelona, Spain: La Merie Business Intelligence, 2007. Accessed November 16, 2007.  http://www.pipelinereview.com/free-downloads/Top20Biologics2006.pdf

2: The future of biosimilars: key opportunities and emerging therapies. London, UK: Reuters Business Insights, 2007

3: Various sources: About Rituxan (rituximab). Biogen Idec & Genentech, 2007. http://www.rituxan.com/lymphoma/RituxanRoleInNHL.jsp.; Remicade (infliximab) - treating your condition. Centocor, Inc., 2007.

4: http://www.remicade.com/remicade/global/treatingyourcondition.html.; All about Intron A. Schering Corporation, 2007. http://www.introna.com/introna/home.action.

5: Miller S, Houts J. Potential savings of biogenerics in the United States. Express Scripts, 2007.

6: What is hemophilia? National Heart, Lung, and Blood Institute, 2007. http://www.nhlbi.nih.gov/health/dci/Diseases/hemophilia/hemophiliawhat.html

7: Various sources: Biopartners submits MS treatment to the EMEA. Pharmaceutical Business Review, 2007.  http://www.pharmaceutical-business-review.com/articlenews.asp?guid=45DBE14A-C077-41E9-8F11-37FCD8D80B75.; Teare I. Biosimilar warfare: the arrival of generic biopharmaceuticals - the Omnitrope decision. BSLR, 2005/2006. http://www.lawtext.com/pdfs/sampleArticles/Biosimilars.pdf.; Zuhn D. Three new biosimilars pass EMEA test. Patent Docs: Biotech & Pharma Patent Law and News Blog, 2007. http://www.patentdocs.net/patentdocs/2007/07/three-new-biosi.html.

8: Note: estimated influence of FoPPs for each category is based on a Reuters Business Insights survey, the findings of which are included in "The future of biosimilars" report and indicate the product groups that will most likely be affected by the introduction of FoPPs.

9: Pisani J, Bonduelle Y. Opportunities and barriers in the biosimilar market: evolution or revolution for generics companies? PricewaterhouseCoopers LLP, 2007.

10: Monoclonal antibody market growth set to outstrip small molecules. Pharmaceutical Business Review Online, 2007. http://www.pharmaceutical-business-review.com/articlefeature.asp?guid=FA5F623C-C82A-4A57-BFE8-D2C7D8648799

11: Amgen announces update to U.S. prescribing information for Aranesp ® and EPOGEN ®: New boxed warning applies to oncology and nephrology incidations for the class of approved ESAs.  Thousand Oaks, CA: Amgen, 2007. Accessed January 5, 2007. http://wwwext.amgen.com/media/mediaprdetail.jsp?releaseID=972417 originally did not expire until 2018 but after a patent challenge, the US government revoked the patent. Genentech has appealed this decision and the patent remains valid and enforceable throughout the appeals process. Source: Rader RA. Biopharmaceutical products in the

12: Genentech received a patent in 2001 for Cabilly II, a combination of Cabilly and Boss technologies, and as a result, now holds the technology that nearly all companies planning to manufacture recombinant monoclonal antibodies must license.  The patent for Cabilly II U.S. and European markets. BioPlan Associates, Inc., 2007 & Pollack, A. Patent held by Genentech is revoked by government.  The New York Times, February 22, 2007. Accessed January 18, 2008. http://www.nytimes.com/2007/02/22/business/22patent.html?r=1&oref=slogin

13: Information ascertained from expert interview with Paul Aebersold

14: Searcy C. How advanced drug delivery technologies can help manage product life cycles throughout pharmaceutical development. Montville, NJ: Drug Delivery Technologies. Accessed January 18, 2008.  http://www.drugdeliverytech.com/cgi­bin/articles.cgi?idArticle=206.

15: EPARs for authorised medicinal products for human use: Biograstim.  London, England: European Medicines Agency, 2008. Accessed May 10, 2009 at http://www.emea.europa.eu/humandocs/Humans/EPAR/biograstim/biograstim.htm g g gyy http://www.emea.europa.eu/humandocs/Humans/EPAR/filgrastimratiopharm/filgrastimratiopharm.htm

16: EPARs for authorised medicinal products for human use: Ratiograstim.  London, England: European Medicines Agency, 2008. Accessed May 10, 2009 at http://www.emea.europa.eu/humandocs/Humans/EPAR/ratiograstim/ratiograstim.htm

17: EPARs for authorised medicinal products for human use: Tevagrastim.  London, England: European Medicines Agency, 2008. Accessed May 10, 2009 at http://www.emea.europa.eu/humandocs/Humans/EPAR/tevagrastim/tevagrastim.htm

18: EPARs for authorised medicinal products for human use: Filgrastim Hexal. London, England: European Medicines Agency, 2008.  Accessed May 10, 2009 at http://www.emea.europa.eu/humandocs/Humans/EPAR/filgrastimhexal/filgrastimhexal.htm

19: EPARs for authorised medicinal products for human use: Zarzio.  London, England: European Medicines Agency, 2008. Accessed May 10, 2009 at http://www.emea.europa.eu/humandocs/Humans/EPAR/zarzio/zarzio.htm

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