The ability of biologics to target specific proteins makes them more effective treatments than small molecule therapies for a variety of medical illnesses and conditions. Biologic therapies such as insulin, erythropoietin and growth hormones have played an invaluable role in treating serious illnesses such as diabetes, anemia and renal diseases. More complex biologics like monoclonal antibodies (MAbs), cytokines and therapeutic vaccines, are now transforming the standard of treatment for cancer, autoimmune disorders and other chronic diseases. It is expected that by 2020 new biologic treatment options will be available for conditions like severe asthma, chronic eczema, atopic dermatitis, and familial hypercholesterolemia across developed markets.
Cancer immunotherapies, which harness the power of the immune system to target and fight malignant tumors, are expected to revolutionize cancer treatment by sparing patients toxic effects of chemotherapy.
Biologics landscape: 2020
The global biologic drug market will top USD 390 billion by 2020, accounting for nearly a third of the global pharmaceutical market by value. The increasing penetration of biologics will in turn lead to higher demand for biosimilars, or follow-on versions of original biologics, in the global pharmaceutical market. Since the first biosimilar approval in the European Union (EU) in 2006, there are now a few hundred biosimilars approved globally. By 2020, biosimilars have the potential to enter markets for a number of key biologics that have current sales of more than USD 50 billion annually. With the approval of the first biosimilar in the US in 2015 and the expected patent expiration of 12 biologics by 2020, estimates suggest that the global biosimilars market could reach USD 25-35 billion by 20204.
Access and affordability
Globally, we are witnessing the rapid spread of a pandemic of non-communicable diseases (NCDs). It is estimated that 38 million people succumb to NCDs like cancer, diabetes, cardiovascular diseases and chronic respiratory disease annually. Today, cancer is the cause of ‘one in seven’ deaths worldwide5, while diabetes now affects nearly ‘one in 11’ adults globally. Biologics like insulins and monoclonal antibodies have emerged as a class of highly effective transformational lifesaving drugs targeted at chronic diseases like diabetes and cancer. The high cost of biologic therapies, however, pushes them out of the reach of many patients, especially those in low- and middle-income countries (LMICs) like India where drug regimens can cost several months’ wages making the treatment of chronic disease simply unaffordable. This large unmet need can only be addressed through high quality, affordable biosimilars that provide cost-effective alternatives to expensive reference biologics. Biosimilars offer patients, physicians and payers a wider option of treatment choices as they compete with original biologic medicines across a growing range of therapy areas. The imperative to improve health care access and reduce the cost of care present growth opportunities for biosimilars manufacturers in both emerging and developed markets. According to investment research organization Sanford C. Bernstein & Co, 70 programs are now in clinical trial stage or later, with 11 approvals in EU, three in US and 44 programs in pivotal trials7. This is likely to result in a highly competitive marketplace over the next five years. The cumulative potential savings to health systems in the five major EU markets and the US, as a result of the use of biosimilars, could exceed EUR50 billion in aggregate over the next five years and reach as much as EUR100 billion.
The experience of the European medical community has been positive in the 10 years since the approval of the first biosimilar in EU. The use of erythropoietin, granulocytecolony stimulating factors and human growth hormone have all increased in this period driven by the availability of biosimilars as well as factors such as expanded indications2. Going forward, insulins and monoclonal antibodies are also expected to experience similar uptake as biosimilar versions become widely available. Infliximab, the first biosimilar MAb to be approved by the EMA in 2013, was offered to patients in Europe at a deep discount of nearly two-thirds the price of the innovator product. Since then, Norway, Denmark and Finland have achieved a near total switch to biosimilar versions of Infliximab.
Biosimilars and Developed Markets Developed markets such as the US, EU and Japan, offer strong growth opportunities for biosimilars manufacturers. As governments in developed markets like EU and Japan strive to rationalize healthcare spends, they are encouraging the entry of high quality yet affordable biosimilars through dedicated regulatory pathways and stringent, abbreviated approval processes. Biocon, through its partner FUJIFILM Pharma, recently launched Insulin Glargine in Japan. This product is the first biosimilar from India and second biosimilar Glargine to be approved in Japan. Industry guidance on biosimilars was released by Japan’s Ministry for Health, Labour and Welfare (MHLW) back in 2009. Nine biosimilars have been approved in Japan between 2009 and 2016, according to Generics and Biosimilars Initiative (GaBI).
In fact, developed markets continue to have the highest number of biosimilar molecules in development – estimated at 29 in Europe, 19 in the US and seven in Japan8. Biosimilars and Emerging Markets High out-of-pocket costs for medicines in emerging markets means physicians are more open to prescribe low-cost alternative therapies. In India, a Deloitte survey found that physicians were willing to prescribe a first-line critical therapy if it was offered at a 60-70% discount. In China, getting on the essential drugs list means mandatory usage by many hospitals; however, it also comes with price cuts of 25-50%. This offers a huge potential opportunity for biosimilar manufacturers committed to develop high quality, yet affordable, world-class biosimilars. Emerging markets, such as the BRICS (Brazil, Russia, India, China and South Africa) and MIST (Mexico, Indonesia, South Korea and Turkey) provide the best future opportunity for manufacturers of biosimilars.
India saw the launch of its first biosimilar way back in 2003, when Dr Reddy’s Laboratories launched biosimilar Rituximab at half the price of the innovator product that is used to treat certain kinds of cancer and autoimmune diseases such as rheumatoid arthritis. A year later, Biocon introduced an affordable recombinant human insulin product developed through an innovative proprietary technology, which enhanced patient access to insulin across India, resulting in improved diabetes management. Since 2008, the Indian biosimilar industry has been growing at a compounded annual growth rate of 30%. There are around 25 Indian companies operating in the biosimilar space, marketing close to 50 products in the Indian market10. Today, Indian patients have access to some of the biosimilars like insulins, insulin analogs, Filgrastim, Trastuzumab, Rituximab, Adalimumab etc. This early experience with developing biosimilars is paving the way for Indian players to capitalize on the unfolding global opportunity. While, Biocon has its core focus on biologics and biosimilars there are other Indian pharma companies who have expanded their pipeline to include biosimilars, as top-selling biologics go off patent worldwide. Biocon, in partnership with Mylan, is developing a high-value portfolio of six biosimilars for oncology and autoimmune indications – Trastuzumab, Pegfilgrastim, Adalimumab, Bevacizumab, Etanercept and Filgrastim - and three generic insulin analogs – Glargine, Lispro and Aspart. The two companies are well-positioned to be among the first wave of entrants to address the biosimilars opportunity globally. They recently moved a step closer to enabling affordable access to these lifesaving drugs in developed markets after the European Medicines Agency (EMA) accepted for review the Marketing Authorization Applications (MAAs) for two of their biosimilars, Pegfilgrastim and Trastuzumab. India, which first issued biosimilar guidelines in 2012, recently announced updated draft guidelines for biosimilars.
The 2016 Guidelines for Similar Biologics incorporates high-end analytics and clinical science to abbreviate the development pathway. However, whilst the timelines may be compressed for Marketing Authorization, the emphasis is on a science-led regulatory pathway that delivers safe and efficacious biosimilars with comparable clinical and immunogenic profiles. Additionally, there is a post-marketing pharmacovigilance plan to monitor safety, efficacy and immunogenicity in a real use setting which truly differentiates these guidelines. In addition to India, many other emerging market countries have either defined biosimilar approval pathways or are finalizing guidelines. South Korea has published biosimilars guidance back in 2009, while China unveiled them in 2015. In Latin America, several regulatory authorities such as ANVISA in Brazil, COFEPRIS in Mexico or ANMAT in Argentina, have developed their own biosimilar regulatory abbreviated pathways.
Evolution of global biosimilar regulations
Global regulations and guidelines need to evolve if biosimilars are to make as much of an impact as small molecule generics have in the past 25 years. ‘Interchangeability’ is an important issue globally that regulators will need to address if patients are to be offered the choice of taking the original biologic drug or substitute a biosimilar drug, just as they currently do with generic versions of chemically synthesized small molecule drugs. US biosimilar regulations have not addressed the issue, while in Europe there are country-specific rules on biosimilar interchangeability.
The lack of clear guidelines on interchangeability with reference biologics is likely to be a cause for concern among physicians until they gain confidence with the usage, experience and outcomes of biosimilars. However, payers are influencing biosimilar decisions in the US even as the government thrashes out guidelines for interchangeability. Leading US pharmacy benefit management (PBM) company, CVS Health, recently left out Sanofi’s blockbuster Insulin Glargine product Lantus from its 2017 formulary, replacing it with Eli Lilly and Boehringer Ingelheim’s biosimilar version of Lantus. Such exclusive arrangements could mean deemed interchangeability for the patient subset covered by the PBM. The naming convention for biosimilars is an issue that needs to be sorted out to ensure that it does not complicate their uptake.
The US FDA has proposed a four-letter suffix to distinguish between a biosimilar and its reference product, similar to the ‘biological qualifier’ proposed by the WHO. The first approved biosimilar in the US filgrastim-sndz (Zarxio) had a common United States Adopted Name (USAN) and a suffix (sndz) that reflected the manufacturer (Sandoz). But the second FDA approved biosimilar, infliximab-dyyb (Inflectra), manufactured by Celltrion, was named using a common USAN with an apparently random suffix devoid of meaning. However, the requirement to add a suffix at the end of a biosimilar’s non-proprietary name could lead to confusion among prescribers and patients.
Biosimilars uptake could also see a boost as more regulators back data extrapolation, which will allow a biosimilar to be approved for multiple indications without undergoing clinical testing in those conditions as long as the reference product itself was approved in those conditions.
Stakeholder education: Need of the hour
Concerns among health care providers and patients over biosimilars acceptance can only be addressed through stakeholder education. Physicians, patients and payers require balanced and adequate education on the role that biosimilar medicines can play. Physicians need to be provided data and evidence that biosimilar medicines offer a safe and efficacious alternative to original biologics.
Moreover, they also need to be helped to understand the broader clinical and health system benefits of prescribing biosimilar products. Patients need to be reassured that biosimilar products are safe and efficacious. Payers need to be educated about the potential offered by biosimilar medicines in ensuring affordable healthcare. Educating these stakeholders about their safety and efficacy will likely require cultivating knowledgeable market and opinion leaders. Biosimilar manufacturers have a key role to play in building trust with these key stakeholders.
Biocon’s strategy of combining products, patients and physician support programs have enabled it to achieve market leadership in the therapeutic areas of diabetology, oncology, immunology and critical care in India. The company is now extending its physician education programs to address the credibility hurdle that needs to be crossed in the minds of biosimilars prescribers.
Biocon organizes an annual breast cancer summit ‘Converge’, which is attended by oncologists from India, Nepal, Sri Lanka and the Gulf countries, where Key Opinion Leaders share clinical data gathered in a real-world setting in order to bust certain myths associated with the use of biosimilars. To enhance scientific capability and credibility in the immunooncology area, Biocon recently organized an Immuno-Oncology symposium with eminent scientists such as Prof. Vijay Kuchroo (Harvard), Prof. Gordon Freeman (Harvard) and Prof. Varsha Gandhi (MD Anderson Cancer Center) as key speakers. This was followed by a round table discussion where Indian Key Opinion Leaders (KOLs) in the field presented their perspectives.
Conclusion
These are exciting times for the life sciences sector as it builds on its understanding of the disease at the cellular and genetic level to usher in new and differentiated therapies into the market. Furthermore, biomedical advances are likely to transform global health with early diagnosis and therapeutic intervention for chronic and killer diseases like autoimmune and cancer. The forthcoming generation of biosimilar products is going to provide affordable access to complex biologics with a promise to enhance the quality of patients’ lives. Governments in major markets like the EU have recognized the potential financial benefit of biosimilars and are driving their uptake. Besides the developed markets like the US and EU, the developing world can also gain from easier accessibility to these cutting-edge treatments that will lead to better health outcomes in these geographies. It is hoped that in the coming years prudent policymaking will result in expansion of biosimilar volumes with governments providing patients with greater access to these drugs.
(The author is President, Marketing at Biocon )
(Courtesy: CPhI Annual Industry Report 2016)