Euro Biosimilars Market Analysis and Reports | Italy Conference Series

Market Analysis - Euro Biosimilars 2018

The Organizing Committee  is delighted to invite you to attend the 11th European Biosimilars Congress  one of its remarkable Pharmaceutical conferences, to be held during April 26-27, 2018 in Rome, ItalyEuropean Biosimilars Congress 2018 brings together scientists, researchers and CROs from around the world. 

Introduction:

Over the past several years, biologics have gained significant traction in the pharmaceutical industry, representing more than $150 billion in global sales in 2013. By 2020 they are predicted to generate $290 billion in revenue and comprise 27 percent of the pharmaceutical market. Forty-eight percent of sales come from 11 biologics that face loss of exclusivity over the next seven years. This, along with the increasing worldwide focus on improving health care access and the cost of care, presents an attractive opportunity for biosimilars manufacturers.

Analysts expect the worldwide biosimilars market to reach $25-$35 billion by 2020. Since the first biosimilar approval in the European Union (EU) in 2006, there are now more than 700 biosimilars approved (~450) or in the pipeline (~250) globally. In major markets like the EU, regulators and payers have recognized the potential financial benefit of biosimilars and are driving their uptake. For example, France has initiated automatic substitution of select biosimilars over the reference products.

In the United States alone, the cost savings from switching to biosimilars are projected to be between $40 and $250 billion over the next 10 years, with the first biosimilar to hit the US market expected to contribute about $5-7 billion in savings.

The recent recommendation by the United States Food and Drug Administration (FDA) to approve an oncology supportive care drug developed by Sandoz represents a landmark for the United States launch and commercialization of biosimilars.

Early biologics, such as insulin, erythropoietin (EPO), and growth hormones, have been invaluable in the treatment of serious illnesses such as diabetes, anemia, and renal diseases. More complex biologics, such as monoclonal antibodies (mAbs), cytokines, and therapeutic vaccines, are helping to revolutionize treatment of cancer, autoimmune disorders, and other difficult-to-treat diseases. For such higher-cost disease areas, biosimilars should be instrumental in expanding access to populations who need these therapies but are unable to access them today.

Biosimilars: Global Markets

As per market researchers the global biosimilars market was valued at $1.8 billion in 2013 and nearly $2.0 billion in 2014. The market is expected to reach nearly $4.0 billion by 2019, with a compound annual growth rate (CAGR) of 15% from 2014 through 2019.

The erythropoietins market segment saw revenue of $438.4 million in 2013 and $501.6 million in 2014. Revenue should reach nearly $1.2 billion by 2019, rising at a CAGR of 18.5% from 2014 to 2019.

Granulocyte colony-stimulating factors (G-CSFs) reached $379.3 million in 2013. This segment is expected to increase from $453.6 million in 2014 to $1.1 billion by 2019, a CAGR of 20.2% from 2014 to 2019.

Source: BCC Research

Importance & Scope:

The European-based pharmaceutical industry makes a major contribution to the Europe, not just in financial terms but also in terms of high-trait employment. Globally Pharma Market ranges from $870-$900 billion and in Europe $260-$280 billion.

A global biosimilars strategy:

Developed markets: Developed markets, with the exception of the United States, represent the greatest biosimilars presence today. Most biosimilars manufacturers have been and remain focused on the developed markets – whether it is for their historic and current opportunities (EU) or for their future market potential (United States, Japan). Dedicated regulatory pathways set the foundation for stringent, abbreviated approval processes which, in turn, have fed investor enthusiasm. Biosimilars adoption in developed markets has been primarily payer-driven, especially in European markets, given payers’ urgent, unmet need to contain public health care expenditures. Further market uptake has been slowed by prescribers’ skepticism and low patient awareness. Still, developed markets continue to have the highest number of biosimilars molecules in development – estimated at 29 in Europe, 19 in the United States and seven in Japan.

Emerging markets: In today’s emerging markets, biosimilars are still nascent, with little to no presence. However, in contrasting emerging markets with developed markets, the limited patient access to affordable biologics and the openness of physicians to low-cost therapies may offer potentially significant opportunities. Today, emerging markets represent a snippet of total world biologic sales in value, less than seven to eight percent (versus 48.6 percent in the United States).ix Treatment rates for flagship biologics are still low compared to developed markets, despite existing demand. For example, the treatment rate of MabThera® in Brazil is three times lower than in the UK and six times lower than in the US.x Additionally, a recent Kantor Health Survey found that 20 percent of emerging market autoimmune patients use a biologic, with the distribution of biologics varying from 29 percent in China to 12 percent in Russia and a mere 6 percent in Brazil.xi This may indicate the presence of large pockets of non-consumption, especially within the growing middle class.

Analysis of selected countries:

 United States

  • FDA approval of the first biosimilar in March 2015 with Sandoz’s Zarxio (filgrastim)
  • About 19 pipeline biosimilar molecules in development
  • Represents about 50% of the global biologics market value and generates about 50% of the sales value growth
  • Pending legislative decisions on data exclusivity period, naming conventions and interchangeability likely to have important implications.

Biosimilars approved in the US

In the US, a legal framework for approving biosimilars was established in 2009, via the Biologics Price Competition and Innovation Act of 2009 (BPCI Act).

The BPCI Act is part of the healthcare reform legislation, which was signed into law on 23 March 2010 by President Barack Obama. The BPCI Act establishes an abbreviated approval pathway for biological products that are demonstrated to be ‘highly similar’ (biosimilar) to, or ‘interchangeable’ with, a US Food and Drug Administration (FDA)-licensed biological product.

FDA is still in the process of developing guidelines regarding these types of products and has issued several guidance documents on the subject.

Zarxio (filgrastim-sndz) was the first product approved in the US as a biosimilar in 2015. To date, FDA has approved four biosimilars within the product classes of anti-tumour necrosis factor-alpha (TNF-α) and granulocyte colony-stimulating factor, and a follow-on biological in the product class of insulin for use in the US.

FDA approved Biosimilars and follow-on Biologicals

Product name

Active substance

Therapeutic area

Authorization date

Manufacturer/ Company name

Amjevita (adalimumab-atto)

adalimumab

Ankylosing spondylitis
Crohn’s disease
Juvenile arthritis
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis

23 Sep 2016

Amgen

Basaglar#

insulin glargine

Diabetes

16 Dec 2015

Eli Lilly/Boehringer Ingelheim

Epoetin Hospira

epoetin alfa

Anaemia (chronic kidney disease, Zidovudine, chemotherapy)
Reduction of allogeneic red blood cell transfusions

Recommended for approval by FDA’s Oncologic Drugs Advisory Committee (ODAC) on 25 May 2017

Pfizer (Hospira)

Erelzi (etanercept-szzs)

etanercept

Axial spondyloarthritis
Polyarticular juvenile idiopathic arthritis
Psoriatic arthritis
Plaque psoriasis
Rheumatoid arthritis

30 Aug 2016

Sandoz

Inflectra
(infliximab- dyyb)

infliximab

Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis

5 Apr 2016

Pfizer (Hospira)

Renflexis (infliximab-abda)

infliximab

Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis

21 Apr 2017

Samsung Bioepis

Zarxio
(filgrastim-sndz)

filgrastim

Autologous peripheral blood progenitor cell collection and therapy 
Bone marrow transplantation 
Cancer 
Myeloid leukaemia 
Neutropenia

6 Mar 2015

Sandoz

*Data collected on 30 September 2016, updated 26 June 2017

Source: US FDA

EU5

  • Most mature biosimilar market representing 80% of global biosimilar spending
  • Performance to date viewed as “disappointing” by select manufacturers
  • Nineteen biosimilar products authorized in four molecule classes: human growth hormone, erythropoietin, G-CSF and tumour necrosis factor (TNF)-inhibitor
  • About 29 pipeline biosimilars molecules in development.
  • World-class dedicated pathway leaving questions of substitutability at the pharmacy level to member states
  • Payer-driven uptake
  • Challenged by continued pressure from strict regulatory decisions, lingering fear from prescribers around biosimilars’ “similarity”, safety and efficacy, debates on automatic substitution and INN prescription.

Biosimilars approved in Europe

In the European Union (EU), a legal framework for approving biosimilars was established in 2003. This framework means that biosimilars can only be approved centrally via the European Medicines Agency (EMA) and not nationally.

EMA first developed guidelines for the approval of biosimilars via an abbreviated registration process during 2005 to 2006, and since then EMA has developed many general and specific guidelines for biosimilars .

Omnitrope (somatropin) was the first product approved in the EU as a biosimilar in 2006. To date, EMA has approved 38 biosimilars within the product classes of human growth hormone, granulocyte colony-stimulating factor, erythropoesis stimulating agent, insulin, follicle-stimulating hormone (FSH), parathyroid hormone and tumour necrosis factor (TNF)-inhibitor, for use in the EU. Three biosimilar approvals have been withdrawn; two for filgrastim biosimilars: Filgrastim ratiopharm in April 2011 and Biograstim in December 2016, and one for a somatropin biosimilar (Valtropin) in May 2012. This leaves a total of 35 biosimilars approved for use in Europe.

EMA approved Biosimilars:

Product name

Active substance

Therapeutic area

Authorization date

Manufacturer/Company name

Abasaglar (previously Abasria)

insulin
glargine

Diabetes

9 Sep 2014

Eli Lilly/Boehringer
Ingelheim

Abseamed

epoetin alfa

Anaemia
Cancer
Chronic kidney failure

28 Aug 2007

Medice Arzneimittel Pütter

Accofil

filgrastim

Neutropenia

18 Sep 2014

Accord Healthcare

Amgevita

adalimumab

Crohn’s disease
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Spondylarthritis
Suppurativa hidradenitis
Ulcerative colitis
Uveitis

22 Mar 2017 

Amgen

Benepali

etanercept

Axial spondyloarthritis
Psoriatic arthritis
Plaque psoriasis
Rheumatoid arthritis 

14 Jan 2016

Samsung Bioepis

Bemfola

follitropin alfa

Anovulation (IVF)

24 March 2014

Finox Biotech

Binocrit

epoetin alfa

Anaemia
Chronic kidney failure

28 Aug 2007

Sandoz

Biograstim

filgrastim

Cancer
Haematopoietic stem cell transplantation
Neutropenia

15 Sep 2008 
Withdrawn on 22 Dec 2016

CT Arzneimittel

Blitzima

rituximab

Non-Hodgkin lymphoma
Chronic B-cell lymphocytic leukaemia

CHMP positive opinion on 18 May 2017

Celltrion

Epoetin alfa Hexal

epoetin alfa

Anaemia
Cancer
Chronic kidney failure

28 Aug 2007

Hexal

Erelzi

etanercept

Ankylosing spondylitis
Juvenile rheumatoid arthritis
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis

CHMP positive opinion on 21 April 2017

Sandoz

Filgrastim Hexal

filgrastim

Cancer
Haematopoietic stem cell transplantation
Neutropenia

6 Feb 2009

Hexal

Filgrastim ratiopharm

filgrastim

Cancer
Haematopoietic stem cell transplantation
Neutropenia

15 Sep 2008
Withdrawn on 20 Apr 2011 

Ratiopharm

Flixabi

infliximab

Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis

26 May 2016

Samsung Bioepis

Grastofil

filgrastim

Neutropenia

18 Oct 2013

Apotex

Inflectra

infliximab

Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis

10 Sep 2013

Hospira

Inhixa

enoxaparin sodium

Venous thromboembolism

15 Sep 2016

Techdow Europe

Insulin lispro Sanofi

Insulin lispro

Diabetes mellitus

CHMP positive opinion on 18 May 2017

Sanofi-Aventis

Lusduna

insulin glargine

Diabetes

4 Jan 2017

Merck (MSD)

Movymia

teriparatide

Osteoporosis

11 Jan 2017

STADA Arzneimittel

Nivestim

filgrastim

Cancer
Haematopoietic stem cell transplantation
Neutropenia

8 Jun 2010

Hospira

Omnitrope

somatropin

Pituitary dwarfism
Prader-Willi syndrome
Turner syndrome

12 Apr 2006

Sandoz

Ovaleap

follitropin alfa

Anovulation (IVF)

27 Sep 2013

Teva Pharma

Ratiograstim

filgrastim

Cancer
Haematopoietic stem cell transplantation
Neutropenia

15 Sep 2008

Ratiopharm

Remsima

infliximab

Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis

10 Sep 2013

Celltrion

Retacrit

epoetin zeta

Anaemia
Autologous blood transfusion
Cancer
Chronic kidney failure

18 Dec 2007

Hospira

Ritemvia

rituximab

Wegener granulomatosis
Microscopic polyangiitis
Non-Hodgkin Lymphoma

CHMP positive opinion on 18 May 2017

Celltrion

Rixathon

rituximab

Chronic B-cell lymphocytic leukaemia
Microscopic polyangiitis
Non-Hodgkin Lymphoma
Rheumatoid arthritis
Wegener granulomatosis

CHMP positive opinion on 21 April 2017

Sandoz

Riximyo

rituximab

Chronic B-cell lymphocytic leukaemia
Microscopic polyangiitis
Non-Hodgkin Lymphoma
Rheumatoid arthritis
Wegener granulomatosis

CHMP positive opinion on 21 April 2017

Sandoz

Silapo

epoetin zeta

Anaemia
Autologous blood transfusion
Cancer
Chronic kidney failure

18 Dec 2007

STADA R & D

Solymbic

adalimumab

Ankylosing spondylitis
Crohn’s disease
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Suppurativa hidradenitis
Ulcerative colitis

22 Mar 2017

Amgen

Terrosa

teriparatide

Osteoporosis

4 Jan 2017

Gedeon Richter

Tevagrastim

filgrastim

Cancer
Haematopoietic stem cell transplantation
Neutropenia

15 Sep 2008

Teva Generics

Thorinane

enoxaparin sodium

Venous thromboembolism

15 Sep 2016

Pharmathen

Truxima

rituximab

Chronic lymphocytic leukaemia
Granulomatosis with polyangiitis
Microscopic polyangiitis
Non-Hodgkin’s lymphoma
Rheumatoid arthritis

17 Feb 2017

Celltrion

Tuxella

rituximab

Wegener granulomatosis
Microscopic polyangiitis
Non-Hodgkin Lymphoma
Chronic B-cell lymphocytic leukaemia

CHMP positive opinion on 18 May 2017

Celltrion

Valtropin

somatropin

Pituitary dwarfism
Turner syndrome

24 Apr 2006
Withdrawn on 10 May 2012 

BioPartners

Zarzio

filgrastim

Cancer
Haematopoietic stem cell transplantation
Neutropenia

6 Feb 2009

Sandoz

*Data collected on 30 September 2016, updated on 26 June 2017

Source: EMA

Japan

  • Limited maturity of the biosimilar market
  • Dedicated regulatory pathway
  • About seven pipeline biosimilar molecules in development
  • Growth potential considered limited today based on the reluctance from both prescribers and patients as well as the general mistrust toward “generic makers
  • A push from payers, which has yet to be seen, may help open up the market.

Brazil

  • Led the way with the development of biosimilars regulations in Latin America and released biosimilars guidance in 2010
  • Reducing the reliance on imported (and high-cost) medicines through policies that favor the expansion of the domestic pharmaceutical industry and public-private partnerships to expand access to drugs
  • International companies have entered the market through partnerships and acquisitions (e.g., Pfizer’s 40% stake in Teuto, Sanofi’s acquisition of Medley and Merck’s joint venture with Supera, co-owned by Cristalia and Eurofarma)
  • The regulatory environment and interest of domestic and international manufacturers are major drivers in expanding the biosimilars market.
  •  Approximately five biosimilar molecules in the development pipeline.
  • Seventy-five percent of physicians surveyed in Brazil considered rituximab difficult to access due to high costs and 77% said they would increase prescription of rituximab if a cheaper alternative were available.

Russia

  • Aims to boost its domestic pharmaceutical market and increase the market share of domestic players from 20% in 2012 to 50% by 2020
  • The strong preference for local manufacturers will require international companies to engage in cooperative partnerships with Russian companies
  • Indicative of the burgeoning domestic industry, a rituximab biosimilar, developed by Russian company Biocad, was the first mAb biosimilar approved in Russia in April 2014
  • About eight biosimilar molecules in the development pipeline.

India

  • Biosimilar guidelines established in 2012
  • 80% of pharmaceutical spend is out of pocket
  • Indian companies have extensive experience with generics and have made in-roads in other countries as well through exports
  • Indian companies grapple with the image of manufacturing as unsafe with poor quality drugs
  • Partnerships between global pharmaceutical companies and domestic companies are helping to improve the quality of biosimilars marketed in India
  • Approximately 19 biosimilars in the development pipeline; large proliferation of non-original biologics
  • Large middle class with growing disposable income who prefer brand name products, so there is a good opportunity for branded Biosimilars.

Approximately 70% of the country’s population is considered rural and will focus on the cost of therapy – a 20-30% discount on originator biologics may not be sufficient.

China
  • Issued draft biosimilars guidelines in 2014; once a clear regulatory pathway for biosimilar approval is established, the market will be very attractive – not only due to the volume potential but also the growing ability to pay
  • Similar to the tight controls requiring international companies to create partnerships or use domestic pharmaceutical distributors, the successful manufacturing and marketing of biosimilars will also require partnerships with domestic companies
  • Lack of physician trust and enthusiasm for non-branded drugs exacerbated by unsafe and counterfeit drugs
South Africa
  • Sophisticated market; generics make up more than 50% of the market
  • Biosimilars guidelines were established in 2010
  • There is a financial pressure on the system overall, and great pressure to utilize generics including biosimilars
  • Several Indian companies have entered the South African market and are key to keeping drug costs low
  • There is a cost containment focus from the government and payer side and a quality focus from the physician and patient side
  • Companies will have to bring in a cost structure that is lower than what currently exists along with the highest quality and safety profiles of their biosimilars
Mexico
  • Established, government-incentivized market for biosimilars
  • Demand spurred by high out-of-pocket health care spending (estimated at +90%)
  • Significant presence of non-original biologicals known as “biolimbos” who have not undergone marketing authorization review consistent with globally accepted standards.
  • Biosimilars development led locally by Probiomed which won six biosimilars approvals, including a version of Rituxan®
South Korea
  • Most mature biosimilar “development” market
  • Enabled by unprecedented support from the South Korean government: 35% of the national medical R&D budget was invested into biosimilars development in 2012xvi
  • Government-set goal for domestic biopharmaceutical companies to win 22% of the global biosimilars market by 2020
  • Twelve biosimilars have been approved and another 36 biosimilars are in the pipelinexvii
  • Leading the race in the high-risk and complex development of monoclonal antibody (mAb) biosimilars with 17 mAbs in the pipeline

A recent study revealed that a third of anti-malaria drugs sold were found to be counterfeit, and 100,000 deaths per year in Africa were linked to counterfeit drugs. Physicians and patients in emerging markets are particularly wary of non-brand name drugs. 75% of emerging markets pharmaceutical growth is expected to come from branded generics. According to a 2013 Roper Report, 79 percent of consumers in developing Asian markets and 61 percent of consumers in Latin American markets only buy products and services from a trusted brand.

Main factors that support a sustainable european biosimilar drugs market:

A study conducted by the consultancy company GFK on behalf of the European Biosimilars Group It analysed the main factors that support a sustainable European biosimilar drugs market. The study revealed that biosimilar medicines provide a major opportunity with considerable benefits, since they lead to cost savings throughout Europe, contribute to the sustainability of National Healthcare Systems and improve patient access to innovative treatments. However, in order to achieve these benefits in the long term, the biosimilar medicines market must continue to be sustainable.

The study concluded that the main factor influencing the sustainability of the biosimilar medicines market and enabling biosimilar drug implementation is that this market must be attractive and deliver continuing benefits, in both the short and long term, to the four key stakeholder groups: physicians, payers, patients and industry. However, the study emphasises that the “attractiveness” and “benefit” concepts are different in each of these groups. In this way, for physicians it involves having more opportunities to treat more patients with appropriate therapies. For payers, it entails cost savings and the financial sustainability of healthcare systems. For patients, it means having improved access to medicines. Finally, for the industry, it involves a reasonable return on investment with the continued attractiveness of R&D investment in new medicines development.

On the other hand, other factors that strongly influence the development and implementation of biosimilars include the prescribing physician’s trust, the complexity of clinical development and the uncertain regulatory framework. In order to increase the prescribing physicians’ trust, they must have a good understanding of biosimilars. In fact, as we already stated in a previous post, the consultancy company PwC (PricewaterhouseCoopers) revealed that only 17% of survey respondents chose the correct biosimilar definition from a list provided (PwC Health Research Institute, Top Issues Consumer Survey, 2015). Therefore, a series of training programs have been established providing clear information about them, including courses, discussion forums, conferences and newsletters. The complexity of clinical development is another important factor because it has a direct impact on obtaining marketing authorisation approval from regulatory authorities, such as the Food and Drug Administration (FDA) in the Unites States, and the European Medicines Agency (EMA) in Europe. The more complex a drug’s clinical development is, the more time is required to obtain the marketing authorisation and the longer it takes to implement it. Finally, the legal framework regulating the development, approval, marketing and implementation of biosimilars, depending on the country, is quite uncertain and vague. However, it is true that Europe has been pioneering in the establishment of a legal framework and guidelines for the approval of biosimilars. In fact, the Spanish Ministry of Health, Social Services and Equality published the Price Referencing Order (SSI/1305/2016) in Spain’s Official State Gazette (BOE) which marks the introduction of biosimilars into the health system.

Critical Analysis:

The capital-intensive nature of the biosimilar business and long gestation periods between initial investment and commercialization require biosimilar players to take a higher level of risk than their counterparts in the smallmolecule generics business, and this can be a significant barrier to entry for many start-ups.

Major Biosimilars Associations in Europe