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From brewing to biologics: Biocon’s Kiran Mazumdar-Shaw changes global health

Kiran Mazumdar-Shaw started as a winemaker and now leads Biocon, India's largest innovative biopharmaceutical company. Ms. Mazumdar-Shaw talked about how to build a multi-billion-dollar global enterprise that is changing the role of global health care and intellectual property.

 

 

Can you tell us how you came up with Biocon?

I graduated from Ballarat Brewing School in Australia in 1975 and became a winemaker. 

My wish is to pursue a career in the brewing industry. However, I am unprepared for the hostility and gender prejudice faced by the Indian brewing industry. 

This rejection made me turn to entrepreneurship and accidentally established Biocon, a new biotechnology company in India, to use my fermentation knowledge to produce enzymes and biopharmaceuticals instead of beer.

 

Have you been smooth sailing since then?

No! As a 25-year-old woman with no business experience and limited financial resources, I face huge credibility and cognitive challenges. In those days, women were not regarded as good entrepreneurs, and biotechnology as an industry was unheard of.

 I dare to start a business in a male-dominated society and a field that no one knows. The prevailing business climate tends to be low-risk companies based on services and generic drugs, and they are reluctant to start innovative companies that are risk-ridden like biotechnology. 

The bank is unwilling to lend me financial support. As professionals worry that I cannot provide "job security", I work hard to recruit people. The supplier told me that they were unwilling to give me credit because they did not have confidence in my ability to operate. 

I successfully overcome these difficulties because I understand that all challenges can be overcome with perseverance and originality.

 

What prompted you to move into the biopharmaceutical field?

After my success with enzymes, I used my biotechnology knowledge to try to influence the health care industry by introducing affordable biopharmaceuticals to patients who need them most. These drugs, called biologics, are developed from living biological sources (such as tissues, cells, and proteins). 

In fact, from biosimilars to biological preparations, as from generics to patented chemically synthesized drugs. What motivated me to accomplish this task was the realization that a considerable part of the world’s population does not have access to essential medicines and cannot afford them when health care exists. 

From wanting to "green the world" through environmentally friendly enzyme technology, my mission became to "cure the world" by developing affordable, life-saving drugs for patients all over the world.

 

Today, Biocon is India's largest fully integrated innovative biopharmaceutical company. Our business footprint covers 120 countries. We invest 15% of the operating income of biopharmaceuticals into research and development. 

In terms of market share, our ability to manufacture high-quality, affordable biologics puts us among the top three global insulin biosimilars. As of March 31, 2017, we reported more than $600 million in revenue and are expected to cross the $1 billion revenue milestone by March 31, 2019.

 

What is the current focus of your biologics project?

We have a series of new biosimilar assets. Biocon is committed to developing affordable treatments for the unmet medical needs of chronic non-communicable diseases such as diabetes, cancer and autoimmune diseases.

 

Biocon's campus in Bangalore. The company recently opened a manufacturing center in Johor, Malaysia.

Biocon is using the power of biotechnology to improve the access to affordable essential medicines for patients with chronic diseases.

What are the advantages of biological agents over traditional treatments?

The ability of biological agents to target, enhance or modulate specific proteins and antigens makes them more effective than small molecule therapies under various medical conditions. 

Biological therapies such as insulin, erythropoietin and growth hormone are of inestimable value in the treatment of diabetes, anemia and kidney disease. More complex biological agents such as monoclonal antibodies (MAbs), cytokines and therapeutic vaccines are changing the standard of treatment for cancer, autoimmune diseases and other chronic diseases. 

Currently, 10 of the top 15 drugs sold globally are biologics. By 2020, we expect new biological treatments for severe asthma, chronic eczema, allergic dermatitis and familial hypercholesterolemia will appear in developed markets. By 2022, biologics are expected to account for 50% of the value of the top 100 drugs sold globally.

 

Different from small-molecule drugs, new biologics and biosimilars are large in volume, more complex, targeted specifically, and have strict production procedures. The time, effort, and money required to analyze and characterize biological agents are four times higher than that of small molecule drugs. 

The manufacturing process starts with fermentation, followed by a multi-step purification process. In addition to determining bioavailability and bioequivalence, clinical development also includes large and long-term clinical trials and complex regulatory approval pathways. 

The cost of developing biosimilars is much higher than that of traditional chemically synthesized generics.

 

Can you talk about the role of innovation in Indian biotechnology?

The Indian biotechnology sector's ability to use recombinant DNA technology makes it possible to provide genetically engineered crops, biopharmaceuticals, vaccines and enzymes. Today, India is the world's largest vaccine producer and largest supplier of genetically modified cotton.

 

Biocon invests 15% of its annual revenue in research and development. It creates a collaborative atmosphere that allows creativity and collaborative research to flow freely, thereby encouraging innovation. 

The company recognizes innovators through a series of incentives, rewards and bonuses. 

But if India is to realize its aspiration to build a $100 billion bioeconomy by 2025, it needs to strengthen the coordination of resources, plans, policies, and priorities to create a self-sustaining virtuous circle of innovation and corporate growth.

 

As one of the earliest biologics companies in India, Biocon's innovation-led strategy has created a series of new biosimilar assets. Today, we have a comprehensive portfolio of 10 published and more undisclosed molecules including insulin and insulin analogs, monoclonal antibodies and recombinant proteins, which are involved in the treatment of diabetes, cancer and immunology.

We also use our new drug research capabilities to promote oral insulin and the world's only clinically validated anti-CD6 targeting molecule to treat psoriasis in the clinic. 

We are also exploring the breakthrough potential of immuno-oncology and developing harmless treatments for patients with malignant tumors. 

Our research in this field spans from many platforms and products of traditional peptides and monoclonal antibodies to therapies based on novel fusion monoclonal antibodies (MAb) and small interfering ribonucleic acid (siRNA).

 

Tell us more about some of your breakthrough innovations.

So far, Biocon has introduced two new biologics and six biosimilars from the laboratory to the market. They are affordable treatments for patients with chronic diseases.

 

Our highest honor is the U.S. Food and Drug Administration (USFDA) approval of Ogivri ™, the biosimilar trastuzumab that we co-developed with Mylan in 2017. We are the first Indian company to obtain a biosimilar approved by the U.S. Food and Drug Administration; it is also the first biosimilar trastuzumab approved in the United States. This brings us into the global alliance of biosimilar experts, which means that we can provide American patients with affordable alternative cancer therapies. 

We launched our branded biosimilars Trastuzumab and CANMAb ™ in India in 2014 and have since launched them in multiple emerging markets. Thousands of patients with HER2-positive metastatic breast cancer are now benefiting from this important drug.

 

In 2017, we launched KRABEVA®, a biosimilar bevacizumab for the treatment of metastatic rectal cancer and other types of lung cancer, kidney cancer, cervical cancer, ovarian cancer and brain cancer.

 

In 2016, we became the first Indian company to launch the biosimilar insulin glargine in Japan, which was launched in India in 2009. Recently, the European Medicines Agency's Committee for Medicines for Human Use (CHMP) recommended that the European Union approve it. 

In fact, we are the first company in the world to commercialize recombinant human insulin (rh-insulin), which was produced in 2004 through the use of Pichia yeast fermentation technology. We now provide a comprehensive portfolio of insulin products to millions of insulin-dependent patients with diabetes worldwide. 

Translating breakthrough laboratory discoveries into clinical success is a major challenge facing the global biopharmaceutical industry. Therefore, Biocon is strengthening its scientific research and development team and participating in strategic cooperation to further improve its effectiveness in this field.

 

At the forefront of new molecules, we are developing, producing and launching biologics in India. In 2006, Biocon became the first company in India to launch Nimotuzumab (BIOMAb EGFR®), a new type of biologic for patients with head and neck cancer. 

In 2013, we launched the pioneering anti-CD6 monoclonal antibody itolizumab (ALZUMAb™) for patients with psoriasis. Thousands of patients in India are benefiting from these affordable therapies.

 

What motivates Biocon to commit to affordable health care?

Biocon's innovative model makes payment ability a success criterion. By leveraging the power of affordable innovation, we view “best-selling drugs” as a way to expand access to one billion patients. Our business model focuses on the right to global healthcare, which is achieved by providing affordable biopharmaceuticals.

 

What role does intellectual property play in your business?

Intellectual property rights guide Biocon's R&D and commercialization strategy by protecting our inventions and innovations. This also helps build our credibility and allows us to benefit from first-mover advantage. Intellectual property also supports product positioning, life cycle management, and asset monetization and evaluation. 

Biocon continues to create wealth of knowledge through an aggressive intellectual property strategy, which recognizes the innovative potential of our products and processes.

 

What are the benefits of using WIPO's Patent Cooperation Treaty (PCT)?

Intellectual property plays a key role in bringing innovation to the market successfully and creating value. The PCT allows innovation-led companies like Biocon to seek patent protection in more than 150 countries through an international patent application. Therefore, this is a cost-effective option. And because the cost of submitting a national application was delayed by 18 months, this gave us more time to formulate a patent and commercialization strategy for the target market.

 

Why is it important for women to engage in science and technology?

My father, the late R.I Mazumdar, convinced me that as a woman, if I did not achieve more than men, I could achieve the same.

 

Science makes the world a better place. Knowledge has no gender. Increased participation of women in science and technology will ensure that research results are quickly translated into useful knowledge that can support human progress. This is an important part of the country's social and economic development.

 

Diversity and inclusion are corporate rules and are embedded in Biocon's core values. We believe that a diverse work environment will promote a culture of innovation and collaboration. For us, diversity is not only to promote gender balance, but more importantly, to appreciate different cultures, backgrounds, generations and ideas.

 

Female scientists bring diversity of thought, creativity and innovation. Scientific organizations realize this and open up more opportunities for women scientists. In fact, Biocon Academy helps close the gender skills gap in the biotechnology field by training many life science graduates (including girls) every year.

The development of biopharmaceuticals (biologics and biosimilars) is a complex process that requires strict production agreements. The clinical development of biological drugs is much more expensive than traditional chemical synthetic generic drugs. (Photo: provided by Biocon).

Women are increasingly becoming an integral part of the Indian scientific community. However, because gender discrimination still exists in society, relatively few women are promoted to leadership positions in science, technology, and business. 

Many people still believe that marriage and family must take precedence over occupation. This explains the gender gap in interdisciplinary research. Studies have shown that although many women study science in India, few are engaged in science or scientific research.

 

What is the secret of your success?

I never give up. My mantra is "Failure is temporary. Giving up is permanent." When the Indian pharmaceutical industry focused on the manufacture and supply of chemically synthesized generic drugs, my mantra helped me guide Biocon in the unknown field of innovation-led biotechnology research. 

I succeeded because I am committed to my dream of changing global health by providing affordable medicines, and also because I am shocked that a large part of the world’s population lacks access to affordable Opportunities for drugs.

 

What advice do you have for women?

If you want to succeed in this field, you need a pioneering spirit. Have the courage to strengthen your convictions and persist in overcoming disappointments and failures. Believe in your wishes and work with goals to achieve these goals.

 

What are the future plans?

I fully believe that the healthcare industry has a humanitarian responsibility to provide affordable essential medicines to patients in need through the power of innovation. My vision is that our diabetes and cancer care research program will change the treatment model. We are working hard to develop affordable, best-selling drugs with the "Made in India" label that will benefit one billion patients worldwide.

References:

1. https://www.wipo.int/portal/en/index.html

 

Biosimilars Advantages, Problems and the Scope

A biosimilar is a biological drug that is highly similar to an approved biological drug. McKinsey predicts that by 2020, the size of the biosimilar market will triple, reaching US$1 to US$2 billion. Based on this alone, we can see that these drugs can change healthcare. A report The Biosimilar Committee (2018) predicts that biosimilars can save up to 1TP250 billion in costs in the next ten years. Can these products improve the sense of gain for patients who rely on biological treatments? What are the challenges and opportunities? This includes the benefits of biosimilars.

A biosimilar is a biological drug that is highly similar to an approved biological drug. McKinsey predicts that by 2020, the size of the biosimilar market will triple, reaching US$1 to US$2 billion. Based on this alone, we can see that these drugs can change healthcare. A report The Biosimilar Committee (2018) predicts that biosimilars can save up to 1TP250 billion in costs in the next ten years. Can these products improve the sense of gain for patients who rely on biological treatments? What are the challenges and opportunities? This includes the benefits of biosimilars.

 

Table of Contents

Biological product The case of biosimilars Biosimilars. The situation in the European Union and the United States The benefits of biosimilars                  Reduce costs through competition                  Improve patient accessibility                  Incentives for innovation                  Biosimilars challenge                  Patient and prescriber education                  Inference problem                  Interchangeability issues                  Rare disease The future of biologics and biosimilars Biologics and Biosimilars regarding Psoriasis Economic Impact of Biosimilars

 

 

What is Biological product?

Biological products are biological molecules derived from living organisms and are used to diagnose, treat and cure many chronic and disabling diseases. These typical large and complex biological molecules-including hormones and monoclonal antibodies-are produced from microorganisms, plants or animal cells using biotechnology. 

The natural variability in the host organism leads to variation between the various batches of active biomolecules being produced. Under normal circumstances, these variability are minimal and will not change biological functions.

Today, biological agents provide one of the most cutting-edge technologies for the clinical prognosis of many diseases. The therapeutic potential of these molecules ranges from diabetes to autoimmune diseases to cancer. 

Although the demand for biologics is great, one of its main disadvantages is the high cost-which is a major obstacle for patients. It is very necessary to understand the benefits of biosimilars.

 

What is the Case of Biosimilars?

Consumers’ cost burden seems to be reduced by the second category of biological products, called biosimilars. Biosimilars are biomolecules that are "highly similar to the approved reference biological drugs." 

To become a biosimilar, a molecule must It exhibits the same characteristics in terms of "structure, biological activity and efficacy, safety and immunogenicity profile" compared with the original reference molecule. Like biological products, biosimilars are also manufactured biologically. Therefore, this process is a natural change, leading to internal differences from the reference drug. These changes make characterization and regulatory approval a challenging task. 

However, if these changes can be proven not to affect clinical safety and efficacy, biosimilars will be considered for approval by regulatory agencies.

 

The reference biological product molecule must pass an "independent" application, containing all data, including clinical trials to prove its safety and effectiveness. 

When the patent for an original biological drug expires, other competing companies can apply for marketing authorization for the corresponding biosimilar product. 

The ultimate goal of a biosimilar drug development project is to prove "biological similarity" to the reference drug, not to establish an independent safety or effectiveness profile. Therefore, biosimilars do not pass traditional clinical trials, but conduct comparative clinical trials to prove that they are not clinically different from the reference molecule. 

Biosimilar molecules can leverage the safety and efficacy knowledge gathered from years of use of reference molecules.

 

From a regulatory perspective, the development of biosimilars does not need to repeat the entire clinical development project like the original reference biologic molecule. This advantage reduces costs for both parties: manufacturers and consumers. 

In addition, it saves a large number of volunteers and patients from participating in unnecessary trials. In general, the approval process for biosimilars is more streamlined, simpler, and cheaper than branded original biologics. Therefore, biosimilars enable patients to obtain medical innovations faster and cheaper without compromising efficacy or safety. 

A comprehensive list of biosimilars approved by the U.S. Food and Drug Administration can be found here.

 

What is the situation regarding Biosimilars in the European Union and the United States?

The European Medicines Agency (EMA) created a special biosimilar approval pathway in the European Union (EU) and approved the first biosimilar (all-rounder 2006). Currently, the European Union is the most mature biosimilar market in the world. 

In fact, the EU regulations have set the tone for the development of biosimilars in other parts of the world. As of March 2018, there are more than 40 biosimilars approved by the European Commission. 

As the pipeline of biosimilars reviewed by EMA continues to expand, this number is expected to rise further.

In the past decade, the EU medical system has observed a clear advantage in the competition in the biosimilar market. It is estimated that by the end of 2018, the EU's biosimilar market will grow to nearly 1.04 billion U.S. dollars.

 

In contrast, the biosimilar market in the United States is still quite flat and is slowly emerging with the formulation of regulatory guidelines. 

The Food and Drug Administration (FDA) only approved the first biosimilar (Felasim) in 2015. As of July 2018, only 12 FDA-approved biosimilars are on the market. 

There is no doubt that the United States is a key biosimilar market. However, many unpredictable factors, including ongoing litigation surrounding patent disputes between innovators, may extend the time to market. 

According to RAND data, biosimilars can reduce the cost of biological products in the U.S. health system by about 1.5 times. $5.4 billion in the next ten years. Now let us look at the benefits of biosimilars.

 

What are the The benefits of Biosimilars?

Reduce costs through competition

Biological medicines can be really expensive. For example, a biological cancer drug may cost hundreds of dollars and thousands of dollars per patient each year. Having multiple biosimilars on the market will break the monopoly of reference drugs and help reduce costs.

 

Improve patient accessibility

With the circulation of more biosimilars, more patients around the world can obtain these treatment options.

 

Incentives for innovation

Before the patent for the reference drug expires, the biosimilar drug cannot be marketed. After the patent expires, having innovative and patentable new biological products may be a necessary condition for maintaining a large market share. Therefore, pharmaceutical companies will be encouraged to invest more in cutting-edge R&D departments to promote innovation.

 

What are the Challenges regarding Biosimilars?

Although biosimilars are inexpensive, they face many challenges in seeking acceptance. Some of the current challenges include:

 

Patient and Prescriber Education

Although biosimilars have existed in the EU for more than a decade, they are still a novelty for people outside of this field. According to a 2014 survey, almost 30% of diagnosed patients said that their drug choice is highly influenced by the identity of the drug manufacturer. 

Both the health sector and the pharmaceutical industry need large-scale education. 

Prescribers may consider biosimilars to be additional work: reviewing clinical data, discussing alternatives with pharmacists, etc. Whether the insurance company agrees to compulsorily switch to biosimilars makes the situation even more complicated. 

Medical society doctors, pharmacists and patients all need to be inspired and then believe in the benefits of switching to biosimilars.

 

Inference problem

Extrapolation is "the process of giving a drug clinical indications without the support of its own or new clinical safety and efficacy studies". Whether biosimilars can be used for off-label indications, and these indications are approved for reference drugs, this is a gray area. 

Appropriate guidelines must be developed for these indications. Otherwise, hospitals and pharmacies will be forced to carry reference molecules and biosimilars at the same time; the cost-effectiveness of prescribing biosimilars will be wiped out.

 

Interchangeability issues

Interchangeability refers to whether switching back and forth between two products does not affect efficacy or safety compared with using each product alone. 

Although there are some guidelines to determine this, there are uncertainties at the local prescriber and pharmacy level. Whether pharmacists can "replace" reference molecules with interchangeable biosimilars without a clear prescription, or vice versa, is another way to seek reconciliation.

 

Rare disease

The treatment of rare diseases often uses "orphan drugs" associated with high costs. Although biosimilars are being developed for these orphan drugs, they face many practical obstacles. First, it is difficult to obtain a large enough, non-heterogeneous population for phase I and phase III trials. In addition, the cost of manufacturing enough batches of biosimilars to conduct batch-to-batch variability studies to establish extensive comparability data may be disproportionately high.

What is the Future of Biologics and Biosimilars?

The biosimilar industry and its regulation have developed by leaps and bounds in the past decade. With some of the most prescribed biologics facing patent expiration in the near future, the biosimilar market is expected to see more growth. 

Market competition promoted by biosimilars poses a threat to the monopoly of the brand-name pharmaceutical industry. 

Typically, pharmaceutical giants are considered to obstruct biosimilar companies in a network of intellectual property rights. 

In the next few years, regulatory authorities need to provide a more specific framework to address some gray areas in the marketing and prescription of biosimilars. This, along with practitioner/consumer education, new development and business models, can lay the foundation for the creation of new large-scale biosimilars. The following are the benefits of biosimilars.

 

What are the developments in Biologics and Biosimilars regarding Psoriasis?

Psoriasis is a common disease that affects 2~3% of the global population. Moderate to severe cases require the use of biological drugs (biological agents) for systematic treatment. Treatment is usually permanent, but these drugs may lose their effectiveness over time. 

When the patent of the original drug (original drug) expires, other companies can produce biosimilar drugs, that is, drugs that are very similar to the original drug (but not exactly the same, because the biologics are derived from active human genes). 

This study conducted in Denmark compared the safety, efficacy, and drug survival rate (i.e. the length of the patient's continuous treatment) of five biologics: adalimumab, etanercept, infliximab, secukinumab and Ustekinumab. 

The study also compared the original drug version and the biosimilar version of etanercept and inflixi. 

The researchers tested data from 3495 treatment series from 2161 patients. The drug survival rate of Ustekinumab is much longer than that of several other drugs. 

The drug secukinumab has the shortest survival rate and therefore the highest risk of stopping treatment. 

Adverse events are also most common in patients taking secukinumab. 

Switching from the original drug to the biosimilar version will not significantly affect the survival rate of the drug. In patients who recovered from skin symptoms, this situation occurred more quickly in patients who used secukinumab as the first biological agent. 

In 10 years, treatment discontinuation occurred in 45.7% (adalimumab), 64.9% (etanercept) and 54.4% (inflix) patients. Sekkizumab and ustekinumab have been taken for only 8 years and 2 years, respectively. 

During this period, 30.3% and 28.8% of patients stopped these treatments. 

Over time, in terms of treatment response, secukinumab had the highest response, followed by adalimumab.

 

What is the Economic Impact of Biosimilars?

The economic impact of non-medical conversion from original biologics to biosimilars:

Here is a systematic literature review to review and summarize the economic impact of non-biological switch (NMS) from a bio-initiator to its biosimilar (ie, the switch to a patient’s drug for reasons unrelated to the patient’s health).

Methods In the past 10 years and the past 3 years, selected scientific conferences were retrieved from PubMed and EMBASE in English publications reporting healthcare resource utilization (HRU) or costs related to biosimilar NMS, And the gray literature on all approved biosimilar biologics (for example, tumor necrosis factor inhibitors, erythropoiesis, insulin and hormone therapy). 

Results: A total of 1,311 publications were retrieved, of which 54 studies met the selection criteria. 

Seventeen studies reported that HRU in the real world or increased costs associated with biosimilar NMS, for example, higher surgery rates (11%), steroid use (13%) and increased biosimilar doses (6-35.4 %). In the study of estimated cost impact related to NMS, 33 cases reported reduction in drug cost, 12 cases reported medical expenses after NMS, but no detailed breakdown, and 5 cases reported NMS establishment and management costs.

 Cost estimation/simulation studies have shown a reduction in costs associated with NMS. However, due to the heterogeneity of research design and assumptions (for example, disease area, discount rate of drug prices, cost composition, population size, study period, etc.), there are large differences between studies. 

Conclusion Real-world research reports indicate that the economic impact of biosimilar NMS exists separately from the cost of the drug. Those who reported this result found that HRU increased in patients with biosimilar NMS. Research on cost estimation is mainly limited to drug prices. 

A comprehensive assessment of the economic impact of NMS should incorporate all important elements of medical service demand, such as drug prices, biological discounts, HRU, NMS plan setting, management and monitoring costs. Sponsor AbbVie.

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