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Biologics are greatly underused across the Asia-Pacific region compared to the USA and Europe. Their high cost – several times the average yearly income per capita – along with limited reimbursement and frequently unaffordable co-pays places them out of reach for most patients and has ignited interest in more affordable alternatives. 

Formal legislation to ensure rigorous regulatory and testing standards for biosimilars (in place of the less regulated ‘copy biologics’) began to appear in 2008–9, with Australia, Malaysia, South Korea, and Japan among the first countries in the region to implement these strict approval requirements. More recently, India (2012) and China (2015) have finalized their own national guidelines. There are currently more biosimilar products in development across the Asia-Pacific region than anywhere else in the world, leading to a wealth of opportunities for investigators and patients to take part in biosimilar clinical trials.

Current access to originator biologics in the Asia-Pacific region   +

Biologics within the countries of the Asia-Pacific region are vastly underused. In China, for example, they make up only 2% of total drug usage, compared with around 10% in Western countries.1

"Oncologists and haematologists across Australia are increasingly finding themselves lacking the essential tools to carry out their job i.e. drugs to treat patients, due to their high cost and lack of reimbursement." 7

In China and South Korea, for example, a survey of rheumatologists found that less than a third of patients who are eligible for treatment with a biological therapy for Crohn’s disease or ulcerative colitis receive their treatment, because of cost and reimbursement issues.2 Lack of affordability is a major factor limiting prescriptions of important biological therapies for conditions such as rheumatoid arthritis, due largely to unaffordable co-pay arrangements and a lack of reimbursement from state health insurance.2 These factors contribute to an overall reduction in treatment best practice and to inequality of care across the region.

  • Owing to cost, biological treatments for ulcerative colitis in China are frequently only prescribed to patients attending large or specialized hospitals.
  • Patients with cancer in Australia are being forced to meet the first AUD $10,000–20,000 for biological treatments not covered under the country’s Pharmaceutical Benefits Scheme (PBS), under co-pay arrangements with the drug manufacturers.3 
  • The same scheme limits reimbursement for biological treatments for rheumatoid arthritis in Australia to patients with severely active disease, subject to many restrictions.4 
  • The cost of available biological treatments (from USD $1000–10,000 per month depending on frequency of bleeding episodes) puts severe restrictions on their use by patients with hemophilia A within China (which accounts for approximately one-quarter of the world’s patients), and prohibits their use as prophylaxis.5 
  • There are also reports suggesting that many patients who are switched to biological agents following an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) are stopping treatment early because of the high costs involved.6

According to leading experts in India and elsewhere, patient access to essential biologics is being restricted by their high cost, which puts them beyond the reach of many of the population.

  • Typically, a course of four injections of a biological treatment for rheumatoid arthritis in India costs Rs 2–3 lakh (€ 2900–4300), which is out of reach for many patients in India.8 

    "Patient access to biologicals in India has been restricted due to their exorbitant cost." 8
    Dr. K Mahendranath, former President of the Indian Rheumatology Association

  • In emerging economies, such as Thailand, patient access to biologic agents for rheumatoid arthritis is severely limited because of their high cost.9 

  • The cost for 1 year’s treatment of a typical biologic for patients with ulcerative colitis is, at around USD $14,000, more than three times the average income per capita in China.2 

  • In Malaysia, physicians are reluctant to use biologics if they are not listed in the hospital formulary and if they are not affordable to the patients, as the current price range is seen to be out of reach for most patients.10

Regulatory guidelines in the Asia-Pacific region   +

Legislation to protect the quality, safety, and efficacy of biosimilars, and maintain rigorous regulatory and testing standards, has existed in some countries in the Asia-Pacific region since 2008, following on closely from the guidance for the development of biosimilars put forward by the European Medicines Agency (EMA) and the World Health Organization (WHO; see table).
  • Some countries, such as Australia, followed the EMA guidance for a number of years before establishing their own national guidelines.
  • Others – notably Malaysia, Japan, and South Korea – have developed their own regulatory pathways from an early stage, building on the example of the EMA and WHO.
  • India finalized its biosimilar legislation in 2012, but as of January 2016 this guidance is undergoing major revision due to problems with interpretation having been encountered.11
  • Biosimilars guidance for China was approved in February 2015.12 

Biosimilars regulation across the Asia-Pacific region

Country

Regulatory agency

Biosimilar regulation

Approved biosimilars*
(February 2015)

Australia

TGA
Therapeutic Goods Administration 

National guidance issued July 2013, updated December 2015.13 Replaces EMA guidance adopted in 2008. Go now!

Yes – referred to as ‘similar biological medicinal products’ (SBMP)

China

CFDA
Chinese Food and Drug Administration

Final guidance issued February 2015.14 Go now!

None – copy biologics only

India

DBT
Department of Biotechnology – preclinical evaluation

CDSCO
Central Drugs Standard Control Organization – clinical trials

Final guidance issued September 2012.15 Major revision underway as of January 2016. Go now!

Yes, theoretically those launched after 2012 (although this has been disputed in the case of some products approved since then)

Japan

MHLW
Ministry for Health, Labour and Welfare

Final guidance issued March 2009.16 Go now!

Yes – referred to as ‘follow-on biologics’ (FOB)

Malaysia
NPCB
National Pharmaceutical Control Bureau
Final guidance issued August 2008.17 Go now!
Yes
New Zealand
Medsafe
New Zealand Medicines and Medical Devices Safety Authority
No specific national guidance issued. EMA guidelines apply.18 Go now!
Yes
South Korea
MFDS
Ministry of Food and Drug Safety, formerly the Korean Food and Drug Administration (KFDA).
Final guidance issued July 2009.19 Go now!
Yes, including world’s first biosimilar monoclonal antibody (2014)
Thailand
TFDA
Thai Food and Drug Administration
No. General biosimilars guidance and specific guidance for biosimilar epoetin both under development.20,21 Go now!
None – copy biologics only (approved through existing generics pathways)

*Products approved before the date of the national regulatory guidance may not have undergone full comparability/biosimilarity testing and are considered ‘copy biologics’ rather than biosimilars.


Approved biosimilars in the Asia-Pacific region   +

Some earlier versions of off-patent biologics – known as ‘copy biologics’ – are already in clinical use in many countries around the Asia-Pacific region and are often mistakenly referred to as ‘biosimilars.’ It is important to realize that these earlier products were introduced before the adoption of country-specific biosimilar regulatory guidance that requires strict biosimilarity/comparability testing and review. As such, ‘copy biologics’ and ‘biosimilars’ should be differentiated from a regulatory perspective. Unfortunately, local reports and statistics do not always reflect this differentiation and may use the term ‘biosimilar’ for both.

  • Conditions that copy biologics and/or biosimilars have been approved to treat in some countries in the Asia-Pacific region include rheumatoid arthritis, ulcerative colitis and Crohn’s disease, neutropenia, hematopoietic stem cell transplantation, some forms of cancer, and growth hormone deficiency.
  • South Korea has been noticeably proactive in the biosimilars field, both in terms of refining their legislation and in terms of product approvals. South Korea was the first country worldwide to approve biosimilar versions of etanercept according to international standards. In addition, the country’s regulators are currently working on class-specific biosimilar regulatory guidelines.22
  • Australia has also been highly active in the biosimilars arena and, as of August 2016, it had approved 11 biosimilars (based on six originators) – second only to the EU. However, Australia has also caused worldwide controversy by announcing that its most recently approved biosimilar, InflectraTM (a biosimilar of infliximab), will be ‘a’ flagged.23 This means the country’s pharmacists are now officially empowered to substitute Inflectra for the originator with no prescriber consultation. Australia is the world’s first highly regulated market to allow pharmacy level substitution of a monoclonal antibody biosimilar for an originator, which has caused concern among Australian professional and patient associations.24 
  • As of April 2016, eight biosimilars have been approved in Japan, including two insulin glargine biosimilars.
  • A recent report has shown that biosimilars in India have witnessed nearly 20% annual growth for the year ending November 2014 and now make up about 2.5% of the overall biologics market.25 However, it is likely that some copy biologics may also have been included in this estimate.

Substantial price reductions for biosimilars have been seen within the Asia-Pacific region:
  • In Japan and South Korea, formal price discount requirements for biosimilars generally range from 30–50% compared with the originator product.In February 2016, Japan’s Ministry of Health, Labor and Welfare proposed a plan to price all biosimilars at a minimum 30% discount in an effort to boost their market share. 
  • In South Korea, biosimilar competition is also driving down the price of originator products, with the price of the original reference product automatically dropping to 70% of its original market price as soon as the first biosimilar product is introduced into the market.26
  • Price reductions of more than one-third of the originator price have been seen with the introduction of recent biosimilars for rheumatoid arthritis in India.1,27 However, the situation in India is particularly complex and there are not always clear distinctions between products approved via the country’s formal biosimilars framework and those that have been licensed on a less rigorous basis.
  • While China has no formal expectations for price reductions, a biosimilar to insulin glargine was introduced in 2013 (prior to the introduction of China’s official guidelines) with a price reduction of 26% compared with the originator.28
The future of biosimilars in the Asia-Pacific region   +

There are thought to be more biosimilar products currently in development across the Asia-Pacific region than anywhere else in the world,29 leading to a wealth of opportunities for investigators and patients interested in taking part in biosimilar clinical trials – see figure below.

India, South Korea, and China are particularly active in biosimilar research efforts, including the development of biosimilars to monoclonal antibodies.30

Biosimilars in pipeline development as of June 201429

Asia Pacific Graph

References   +

  1. PharmAsia News, 19 October 2014. China biosimilar discount expectations may deter MNCs. https://www.pharmamedtechbi.com/publications/pharmasia-news/2014/10/19/china-biosimilar-discount-expectations-may-deter-mncs. Accessed 26 February 2015.
  2. Decision Resources, 24 September 2012. In both China and South Korea, less than one-third of surveyed clinicians’ patients who are eligible for a biological therapy are actually receiving one for Crohn’s disease or ulcerative colitis. http://decisionresources.com/News-and-Events/Press-Releases/UC-CD-China-South-Korea-092412. Accessed 22 January 2015.
  3. Herald Sun, 4 May 2014. Thirty-six wonder drugs could extend or save the lives of cancer sufferers, but our leaders just need to fund them. http://www.heraldsun.com.au/news/thirtysix-wonder-drugs-could-extend-or-save-the-lives-of-cancer-sufferers-but-our-leaders-just-need-to-fund-them/story-fni0fiyv-1226905196352?nk=359f8fb486b5e2ca06bf9aa1fbabfd62. Accessed 26 February 2015.
  4. Australian Government Department of Human Services. Rheumatoid arthritis. http://www.medicareaustralia.gov.au/provider/pbs/drugs2/rheumatoid.jsp#N1008F. Accessed 26 February 2015.
  5. Thomson Reuters BioWorld, 2014. Biosimilars: A global perspective of a new market opportunities, threats and critical strategies 2014. http://www.bioworld.com/sites/default/files/img/biosimilars2014_-_sample_0.pdf. Accessed 10 December 2015.
  6. Wu B, Wilson A, Wang FF et al. Cost effectiveness of different treatment strategies in the treatment of patients with moderate to severe rheumatoid arthritis in China. PLoS ONE (2012) 7:e47373.
  7. Cancer Drugs Alliance. Clinicians. http://www.cancerdrugsalliance.org.au/page/6/clinicians. Accessed 3 February 2015.
  8. GaBI Online, 25 October 2012. Reliance Life Sciences starts ‘similar’ infliximab trial in India. http://gabionline.net/Biosimilars/News/Reliance-Life-Sciences-starts-similar-infliximab-trial-in-India. Accessed 22 January 2015.
  9. Osiri M & Maetzel A. The economic burden of rheumatoid arthritis: Asia/Thailand perspective. Handbook of Disease Burdens and Quality of Life Measures (2010): 1733–1750.
  10. Solehan HM, Said SMS, Shaharir S & Rajalinghamb S. Rheumatoid arthritis: Refractory to infliximab, a tumor necrosis factor inhibitor. J Clin Med Res (2011) 3:270–274.
  11. The Economic Times, 18 November 2015. Health ministry plans to revamp regulatory rules for biosimilar drugs. http://economictimes.indiatimes.com/industry/healthcare/biotech/healthcare/health-ministry-plans-to-revamp-regulatory-rules-for-biosimilar-drugs/articleshow/49823305.cms. Accessed 29 January 2016.
  12. Ropes & Gray, 6 March 2015. China announces final biosimilar guideline. http://www.ropesgray.com/news-and-insights/Insights/2015/March/China-Announces-Final-Biosimilars-Guideline.aspx#sthash.Oe8LvHeV.dpu. Accessed 12 March 2015.
  13. Australian Government Department of Health. Regulation of biosimilar medicines. https://www.tga.gov.au/publication/evaluation-biosimilars. Accessed 27 April 2016.
  14. Chinese Food and Drug Agency. Technical guideline for the research, development and evaluation of biosimilars. http://www.sfda.gov.cn/WS01/CL0087/115103.html. Accessed 12 March 2015.
  15. Government of India, 2012. Guidelines on similar biologics: Regulatory requirements for marketing authorization in India. http://dbtbiosafety.nic.in/Files%5CCDSCO-DBTSimilarBiologicsfinal.pdf. Accessed 22 January 2015.
  16. Japan Biosimilars Guidance. Guideline for the quality, safety, and efficacy assurance of follow-on biologics. http://www.pmda.go.jp/english/service/pdf/notifications/PFSB-ELD-0304007.pdf. Accessed 22 January 2015.
  17. Abas A. Regulatory guidelines for biosimilars in Malaysia. Biologicals (2011) 5:339–342. http://www.sciencedirect.com/science/article/pii/S1045105611000741. Accessed 11 December 2015.
  18. Medsafe, New Zealand Medicines and Medical Devices Safety Authority. Biosimilars. http://www.medsafe.govt.nz/profs/RIss/Biosimilars.asp. Accessed 22 January 2015.
  19. National Institute of Food and Drug Safety Evaluation. Guidelines on the evaluation of biosimilars. www.nifds.go.kr/en/research/bio.jsp. Accessed 22 January 2015.
  20. Thailand Food and Drug Administration. Specific guidance for erythropoietin biosimilars. http://drug.fda.moph.go.th/zone_admin/files/Specific%20Guidance%20for%20Epo%20-%20Biosimilars_01Apr.pdf. Accessed 3 February 2015.
  21. Thailand Food and Drug Administration. http://www.fda.moph.go.th/fdamain.stm. Accessed 3 March 2015.
  22. Pharma & MedTech Business Intelligence, 15 September 2015. Korea mulls new biosimilar guidelines as pipeline surges. https://www.pharmamedtechbi.com/Publications/Pharmasia-News/2015/9/15/Korea-Mulls-New-Biosimilar-Guidelines-As-Pipeline-Surges?elsca1=pan&elsca2=rss&elsca3. Accessed 2 November 2015.
  23. AJP.com.au, 24 August 2015. GBMA welcomes the ‘a’ flagging of biosimilar infliximab. https://ajp.com.au/news/gbma-welcomes-the-a-flagging-of-biosimilar-infliximab/. Accessed 2 November 2015.
  24. Open letter to the Australian Minister for Health from the Arthritis Australia, The Australian Rheumatology Association, Crohn’s and Colitis Australia, and the Gastroenterological Society of Australia, 8 September 2015. https://arthritis.sslsvc.com/our-services/clinical-trials/patient-safety-alert-biosimilar-inflectra-infliximab-added-to-pbs/Final-Joint-letter-to-Minister_PBACre-a-flagging-biosimilars.pdf. Accessed 2 November 2015.
  25. The Financial Express, 27 December 2014. Biosimilars are the next big thing for Indian pharma. http://www.financialexpress.com/article/economy/biosimilars-are-the-next-big-thing-for-indian-pharma/23516/. Accessed 26 February 2015.
  26. GaBI Online, 17 January 2014. Biosimilar trastuzumab approved in Korea. http://www.gabionline.net/Biosimilars/News/Biosimilar-trastuzumab-approved-in-Korea. Accessed 26 February 2015.
  27. FiercePharma, 9 December 2014. AbbVie's Humira competition begins with Cadila's biosimilar launch in India. http://www.fiercepharma.com/story/abbvies-humira-competition-begins-cadilas-biosimilar-launch-india/2014-12-09. Accessed 22 January 2015.
  28. PharmAsia News, 12 July 2013. Sanofi sees emerging market led by China the second largest insulin opportunity after U.S. https://www.pharmamedtechbi.com/publications/pharmasia-news/2013/7/12/sanofi-sees-emerging-market-led-by-china-the-second-largest-insulin-opportunity-after-us. Accessed 22 January 2015.
  29. BIOPHARMA. Biosimilars/Biobetters Pipeline Database. http://www.biosimilarspipeline.com/. Accessed 26 February 2015.
  30. Citeline. Trialtrove. http://www.citeline.com/products/trialtrove/. Accessed 26 February 2015.
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