All about Biologicals and Biosimilars - opportunity in India

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This article content is written by Dr. Prashant Mishra and posted on behalf of him. This article explains Biologicals and Biosimilars in details. Definitions, benefits, companies deals in, opportunity in India and finally Dr. Prashant Mishra pen down his valuable opinion.

Table of Contents

    Biopharmaceuticals:

    What are biologic drugs?

    A large Protein molecule typically derived from living cells and used in the treatment or prevention of diseases. Include therapeutic proteins, DNA, monoclonal antibodies and fusion proteins. Often 200 to 1,000 times the size of a small molecule drug and far more complex structurally.

    Examples:

    1. Human Growth hormone
    2. Human insulin
    3. Erythropoietin
    4. Vaccines
    5. Monoclonal antibodies
    6. Anti-sense drugs
    7. Enzymes
    8. Cytokines and peptides
    9. Cell therapies, etc.

    What are Biosimilars?

    Biosimilars are legally approved subsequent versions of innovator biopharmaceutical products made by a different sponsor following patent & exclusivity expiry of the innovator product. Because of structural & manufacturing complexities, these biological products are considered as similar, but not generic equivalents of innovator biopharmaceuticals. In simple terms Biosimilars are non-innovator or copy products of the original biologic drug and are also cheaper.

    DEFINITION OF BIOSIMILARS:

    1. By WHO

    SBP (Similar Biologic Product) A biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product.

    2. BY US FDA

    FOB (Follow-On Biologic)

    A biological product that is highly similar to a U.S. licensed reference biological product with no clinically meaningful differences in terms of the safety, purity and potency.

    Unlike generic medicines where the active ingredients are identical, biosimilars – by definition are not likely to be identical to the originator biologic. Similar to Snowflakes Biologics made by different manufacturers differ from the original product and from each other.

    Production of biologics

    • The genetic code of a chosen protein, such as immune system antibody is identified and replicated by combining different segments of DNA to build a functional DNA sequence
    • This DNA sequence is introduced into the host cell of a living organism, such as mammal cells altering the cell to produce the chosen protein.
    • These genetically modified cell lines are carefully selected (MASTER CELL LINE) and cultured in large bioreactors before the biologic medicine is extracted through complex and lengthy purification process.

     

    Biosimilars benefits, Role and Concerns

    Benefits of Biosimilars:

    The development of biosimilars allows for wider and, as important, earlier access to these agents because of their lower cost and consequently greater affordability. Lower cost is expected not only to improve cost efficacy ratios, but also to improve drug access.

    1. Greater affordability
    2. Improved Drug Access
    3. Wider application

     

    Emerging Role of Biosimilars:

    1. Countries around the world- growing, aging population ---> ↑ in chronic disease.
    2. Expanding demand for good-quality healthcare ---> challenge of controlling healthcare expenditure.
    3. The safe and regulated introduction of biosimilars into the market has been forecasted to increase access to much needed biologic medicines and reduce costs.

    Concerns with Biosimilars:

    1. The two biosimilar products have different origin.
    2. The two biosimilars may have same therapeutic effect.
    3. They may have different side effect and toxicology.

    Hence Biosimilars require thorough testing

    What is biosimilarity?

    • “Biosimilarity” is the regulatory term used to denote the comparability between a biosimilar and its reference medicinal product.
    • Regulatory bodies across the world including India, recommends a stepwise approach to demonstrate biosimilarity between a proposed medicine and the original biologic.
    • The aim is to demonstrate no clinically meaningful difference in terms of safety, potency and purity.

    Mostly Commonly used BRM’s in Rheumatology:

    1. 1. Infliximab: A monoclonal Ab to TNF, proinflammatory cytokine. Toxicity: Respiratory infection, fever, hypotension. Predisposes to infections (reactivation of latent TB).
    2. Rituximab: A monoclonal antibody to CD20 surface immunoglobulin. Clinical use: Lymphoma.
    3. Etanercept: Recombinant form of human TNF receptor that binds TNF.

    Ranbaxy lauched Indias first Biosimilar of Infliximab – Infimab in Dec 01 2014

    • Clinical effectiveness of Infimab coupled with cost effective pricing will enable more number of patients to get access to biologic treatment in india.

    Etanercept - Etacept

    • Cipla one of leading pharmaceutical company announced the launch of first biosimilar of etanercept in India, known as etacept, in Arpril 2013.

     

    Intas launched biosimilar version of Rituxumab – Mabtas in India in April 2013 in order to make treatment of NHL cost effective.

    Limitations of patent Biologics

    • Injection-site reactions are the most frequent adverse events. The severity varies from mild redness to deep inflammation and necrosis.
    • In most cases, the treatment can be continued and the severity of reactions will decrease with time.
    • Like all foreign proteins, monoclonal antibodies may induce urticaria, angioedema, anaphylactic reactions, and serum sickness.
    • Production of inactivating antibodies to the drug may occur, classically with infliximab, and may be prevented by concomitant administration of low-dose methotrexate.
    • Alopecia is a common complication of IFN-α.
    • A nonspecific, highly pruritic “dermatitis” is frequent in patients receiving IFN and ribavirin for hepatitis C.
    • Induction or exacerbation of various immune-mediated disorders, especially lupus erythematosus, has been reported with interleukin 2, IFN-α, and antitumor necrosis factor α.
    • Granulocyte colony-stimulating factor may induce various neutrophil dermatoses, including Sweet’s syndrome and pyoderma gangrenosum, and can exacerbate psoriasis.

     

     

    According to a recent report by Morgan Stanley, as many as nine drugs in the biologics category have either gone off patent or will do so by 2025. Their total revenue was $62 billion (around Rs 4.3 lakh crore) in 2018. This creates a major opportunity for their respective biosimilars. The research firm estimates that revenue of these biosimilars will grow by 24 per cent annually for seven years to $13.3 billion in 2025 (around Rs 93,000 crore) in the US and Europe. That offers a big opportunity.

    What is the opportunity for India?

    According to a report by Associated Chambers of Commerce of India (Assocham), the global market for biosimilars will be $240 billion and the Indian market will be over $35 billion by 2030. Indian pharma companies including Biocon, Glenmark Pharmaceuticals, and Zydus Wellness are actively focusing on the biosimilars market. Biocon, for instance, earned Rs 1,517 crore or nearly 28 per cent revenue from biosimilars in FY19.

    Indian scenario

    Biosimilars entry in to the Indian market In India, biosimilars are called as "similar biologics". India has come a long way since the first "similar biologic" was launched in 2000 for hepatitis B when no specific guidelines had been established for approval and marketing of a biosimilar in India. .

    The active partake of the Indian companies in the biosimilars space is seen by the fact that 201 active biosimilars are in the pipeline of 52 Indian companies.

    A report by of Associated Chambers Commerce of India (Assocham) predicts that by 2030 the global market for biosimilars will have reached $240 billion and the Indian market will be at a booming $35 billion . If the figures are right, this indicates that the Indian market is ripe, lucrative and full of potential, still left to be explored.

    Another report by Association of Biotechnology Led Enterprises (ABLE), India’s biologics market will grow at a compound annual growth rate (CAGR) of 22 percent to hit $12 billion by 2025.

    98 biosimilars were approved by September 2019.

    Some Facts
    • Global market for Indian non-innovator products-approximately USD 1.5 billion per annum with annual growth rate of 27%.
    • Estimated exports of Indian biopharma products increasing at rate of 47%. In India-good acceptance of non-innovator products amongst health care professionals and patients.
    • Several home-grown biopharma industries now actively developing and marketing noninnovator products in India.
    • To simplify the regulatory pathway to get faster approvals and cGMP manufacturing processes assuring quality, safety, and efficacy, the revised ‘Guidelines of Similar Biologics’ was released by Central Drugs Standard Control Organisation (CDSCO) and DBT on August 15, 2016. This encouraged more than 2700 biotech startups in the country,100 biotech incubators, and 600 biotech companies. The numbers are going to increase by four to five fold in the next five years.

    Just Read ( European pharmaceutical manufacturer ) in article

    Demand in Europe and the USA is expected to sustain longer term growth rates as these markets open-up further to biosimilar encroachment and encourage new entrants. Undoubtedly, the lower cost of manufacturing in India makes biosimilars exports attractive to Western markets though initial market entry may be slowed by high clinical development costs. Data also suggests that 2019 will see a larger number of Western-Indian partnerships bringing new biosimilars to patients in both the EU and USA.

    The research highlighted that unlike its small molecule industry – which improved rapidly in the 2018 league tables – the bio industry in India is still viewed by international pharma as substantially behind the leading markets in terms of quality and innovation. Notably, the top ranked nations of the United States, Germany, and Japan, and the second tier of advanced nations, Sweden, Ireland, Switzerland, the UK, France and Korea.

    But our Problem is quality and innovation ,read the comment below

    However, data from CPhI shows that India also received the second lowest overall scores for ‘quality of biologics manufacturing’ and ‘biologics innovation

    Top companies manufacturing Biosimilars worldwide:

    Humira, Remicade, Enbrel, Aranesp, Rituxan, Sandoz, Teva, Hospira, Pfizer, STADA Arzneimittel, Mylan, 3SBio, Qilu Pharmaceutical, Shanghai Fosun Pharmaceutical, Biocon, Dr. Reddy's Laboratories, Probiomed, Biosidus, Celltrion, LG Life Sciences.

    Leading biosimilar companies based in the US, Western Europe and Israel:

    • Hospira
    • Mylan
    • Sandoz
    • STADA Arzneimittel
    • Teva Pharmaceutical Industries

    Leading biosimilar companies based in China:

    • 3SBio
    • Beijing ShuangLu Pharmaceuticals
    • Qilu Pharmaceutical
    • Shanghai Fosun Pharmaceuticals
    • Tonghua Dongbao

    Leading biosimilar companies based in India:

    • Biocon
    • Dr. Reddy's Laboratories
    • Intas Biopharmaceuticals.
    • Reliance Life Sciences
    • Hetero
    • Zydus
    • Cadila

    Leading biosimilar companies based in Latin America:

    • Probiomed
    • Biosidus
    • Amega Biotech

    Profiles of leading biosimilar companies based in the rest of the world:

    • Celltrion
    • LG Life Sciences
    • Dong-A
    • Bioton
    • Biocad