Updated on 8 March 2015
The growing demand for affordable biosimilars by patients will see it grow exponentially not only within Asia but across the globe
Singapore: A report by MarketsandMarkets estimates APAC to be the fastest growing market for biosimilars, accounting for nearly 29 percent of the global biosimilars market. Countries like Singapore and South Korea have invested significantly in manufacturing and are well poised to grow in this space. South Korea in particular has played a leading role in trailblazing the path for biosimilar development and products launched by Korean manufacturers have gained approval in highly regulated European markets. India, Taiwan, and China are displaying strong potential to emerge as prominent players and many companies from these countries have already launched their products in to the market. Government initiatives in these countries are also fuelling the launch of biosimilars.
Speaking to BioSpectrum, Ms Charu Manaktala, medical director, Clinical Strategy, Strategic Drug Development-Asia, Quintiles, mentioned, "As far as the pharmaceutical industry is concerned, many Asian companies, especially in India, are experienced in the business of generics. Many companies that have grown primarily on the basis of generics are now looking to diversify into areas with higher risks but also potentially higher returns when compared to traditional generics and possibly less competition. Biosimilars offer an interesting and viable diversification option for such players."
Several Asian companies have been increasing their focus on biosimilars, terming it a long term prospect. Biosimilars are a clear potential for players in emerging Asian countries as there is a need to broaden healthcare coverage with limited budgets. "Few factors like increasing pressure to decrease medical expenses and insurance premiums, deepening deficit in government healthcare budgets due to the costs of medicine, growing demand on high quality medical treatments at affordable costs, patent expiry of original biopharmaceutical, technologic advances has fueled biosimilar product development in Asian countries," said Dr Stanley Hong, president, Celltrion Healthcare Korea.
Biosimilars provide low-cost alternatives in comparison to innovator products, thus enabling important biological medicines to be available at affordable costs for patients. In India, the biosimilar etanercept has been priced at 70 percent of the branded price and the launch of infliximab in South Korea resulted in 70 percent reduction in price of its originator drug. The approval of biosimilars versions not only benefitted patients but also reduced the governments' expenditure on healthcare. "Apart from financial gains, observed, Ms Noelle Sunstrom, CEO, Neuclone, "We see biosimilars as providing effective drugs to millions of patients, that up to now have been impossible for many in Asia to access due to the very high price and profit margin of the originator products.
Cost-competitive biosimilars will assist governments and health providers across Asia deliver better healthcare while controlling costs. Biologics in oncology and other areas of medicine, have changed the way many of chronic and life-threatening illnesses were treated. These medicines act on very specific targets and, as a result, provide high efficacy with relatively limited toxicity. High prices of innovator biologics are straining the healthcare budgets in markets where these medicines are reimbursed; in markets where they are not reimbursed they are unaffordable to most people. Because of these factors, many types of companies are joining the biosimilars stampede - traditional big pharma, biotech, generic players, and new entrants to the bio pharma industry, such as Samsung and Fuji Film."
With new products penetrating, the current $1.9 billion biosimilars market is expected to swell up to $35 billion by 2020. Monoclonal antibodies represent the largest sector of the biologics market and a significant opportunity for biosimilars developers, driven by the rising incidence and prevalence of cancer and the therapeutic success of these targeted therapies. Patents for top-selling monoclonal antibody drugs such as Remicade, Humira, Avastin,
MabThera/Reditux, and Herceptin will expire within the next decade, opening the door for biosimilars. Just as generic drugs, which compete with chemical-based medicines that previously enjoyed market exclusivity, biosimilars compete with biologics once their patents have expired. Like most markets, a competitive biologics market can benefit consumers by lowering prices and increasing quality.
One of the key drivers of this market is the increasing number of patent expirations. "Of the current $170 billion market worldwide, $48 billion of spending for biologic medicines will lose exclusivity in the next five years, and this poses significant opportunity for development of biosimilars," observed, Dr Murtaza Khorakiwala, MD, Wockhardt.
Unlike generics, commercialization of biosimilars poses many challenges. Although many companies are keen on getting a share in the biosimilars market given its promising outlook, bringing these complex molecules from bench to launch can be a challenge. Developers have struggled to address major hurdles such as high development cost, unsettled legislation and regulation and complex intellectual property terrain. The main hurdle is that the new molecule must be close enough to the originator molecule, regardless of the complexity of the originator. Companies developing these molecules must demonstrate the similarity of the compound by performing a side-by-side comparison with the originator molecule. Also, unlike the manufacturing processes of small-molecule drugs that can be chemically synthesized and easily replicated, a biologic is produced from living organisms and has more complexity and heterogeneity. "To make a successful biosimilar product one must invest in expertise in diverse sophisticated analytics and be able to tune to structure of the antibody to meet very high standards of comparability," noted Ms Sunstrom.
The development of biosimilars is a long process that is fraught with risks and costs. A single biosimilar molecule takes nearly 7-8 years to develop, with clinical trials that may involve around 500 patients. The tougher regulations, significant clinical trials and comparison trials, all add to the mounting costs.
Mr William Marth, president and CEO of Teva's Americas was reported by the Wall Street Journal as estimating the cost of developing a single biosimilar to be about $200 to $300 million, far higher than developing a generic drug.
"Typically, it would take at least around 4-6 years for development for biosimilars and its formulation," highlighted Dr Khorakiwala, "The approval timeline is anywhere from 2-3 years after submission of marketing authorization application with full dossier containing clinical study data."
Another significant challenge is the need for a specialized sales force for marketing the drug to the prescribers. "Unlike generics, explained Ms Manaktala, "substitution at the pharmacy level is not a given for biosimilars. Hence, there is the need to effectively communicate with prescribers about the safety and efficacy of biosimilars in order to generate new prescriptions."
Apart from this, many products have a need for nurse educators to train the end users. Also, there is a need to have a device or a delivery system that can actually differentiate the product from its competitors, both the innovator product as well as other biosimilars.
"Access to low-cost manufacturing is yet another important consideration for commercializing these products effectively. Overall, the commercialization of biosimilars involves considerations similar to those relevant for New Biological Entities and branded generics. This is one of the important reasons why we see most players entering this field with one or more partnerships," added Ms Manaktala.
Physicians and payers will play a key role on its uptake based on safety and pricing. Since it is produced from living organisms, building and maintaining a suitable cGMP manufacturing facility underlies critical success parameter for biosimilars. "The largest challenge will be to educate physicians, payers and patients that biosimilars are equally effective and safe as the innovator therapy," said, Mr Amit Munshi, CEO, EPIRUS Biopharmaceuticals.
Safety assessment is an important aspect that is considered during development and marketing of the biosimilars. Dr Khorakiwala, stated, "Biosimilars, being natural biomolecules, are expected to be safe without any major surprises on long-term therapy. Well characterized molecules like insulins and erythropoietin, are predictably safer because of the current understanding between structures and function of different structural elements of these molecules. The safety data available for the reference product is usually taken into account for establishing the benchmark for the safety evaluation of biosimilars. From Wockhardt‟s experience, the biosimilars which are developed and marketed across global markets, have always been the preferred products of choice equally by the health care professionals and patients in our key markets. Wockhardt‟s products have been in the market for over a decade and are well accepted by the patient population without any major adverse reactions being reported - which clearly demonstrates the long term safety of biosimilar products."
Regulatory hurdles-the Need for Harmonization
Biosimilars regulation poses a number of scientific and regulatory challenge for authorities. While some countries have designed a set of regulatory guidelines as well as product specific requirements, there is no general consensus as to a single, simple mechanism that leads to approval of generic small molecules all over the world. Many Asian countries like India, Korea, Australia, China and Japan have drafted regulations for biosimilars, and these are generally less stringent in comparison to Europe and the US, thus enabling more manufacturers to enter the field. However, there is no harmonization of the regulations across countries, posing significant challenges for biosimilar developers as regional differences in data requirements and regulatory approvals, dictate the need to replicate certain aspects of a biosimilar development program, tailored to the requirements of specific regions.
"Regulatory harmonization is highly needed to lessen development cost and commercializing price of biosimilars. Biosimilars has social value, when it is supplied in affordable level of price. Rigorous regulatory investigation to ensure product's quality is inevitable, but regulatory and statutory complexities should be addressed to get rid of theses hurdles and elaborate accessibility of biologics," mentioned Dr Hong.
Though the European Union has established guidelines for biosimilars, the US has so far no proper guideline for the approval process. Many drugmakers consider the formulation of the US guidelines as a major step towards growth in the biosimilars business. "Navigating the regulatory pathway in most of the world markets is a challenge - the situation in many countries regarding the procedure used to evaluate biosimilars is not always clear. The harmonization of regulatory pathway worldwide for commercialization of biosimilars to have a sound clinical development strategy is extremely critical," added Dr Khorakiwala.
Recently, WHO has planned to harmonize the regulations for biosimilars thus paving the way for their development and approval. As per sources, there is an initiative under the International Pharmaceutical Regulators Forum to have a bigger convergence and harmonization of the regulators' view and approach to this particular group of products.
"The introduction of high quality, safe, and effective Biosimilars has the potential to expand access in many markets in the Asia Pacific region to these important medicines. The Asia Pacific region's regulatory environment is diverse, ranging from highly regulated markets with experience approving Biosimilars to those where draft guidance has only recently been developed. Pfizer is looking to work with local authorities across the region to ensure that Biosimilar approval guidelines meet the highest standards set by WHO. At Pfizer, we aim to work closely with local organizations to tailor our approach for individual markets," said Ms Diem Nguyen, general manager, Biosimilars, US Promoted Brands, LOE Portfolio Head, Pfizer.
The challenge for both regulators and the biopharmaceutical industry in this constantly changing environment is to maintain a reasoned approach and resolve the issues in a way that keeps the science of biosimilars moving forward for the benefit of patients around the world.
Despite some challenges, therapeutic development of lower cost biosimilars will inevitably enter the drug market in the near future, increasing the market competition and patients' access to the more cost-effective therapies. Asian companies are currently exploiting the clinical development, regulatory approval, and commercialization strategies of multi-national biopharma companies in order to maximize the commercial potential of their biosimilars. It is also important for regulatory bodies and governments to support the local market through enforcing stronger regulations and incentives to foster growth and give a new fillip to this burgeoning sector.
The growing demand for affordable biosimilars by patients will see it grow exponentially not only within Asia but across the globe. "Asia is a very significant market opportunity today and especially tomorrow," concluded Ms Sunstorm, "In a few years Asia will be the largest market globally for biosimilar products that provide the right mix of quality, price and proven medical value to patients. Soon, China will have the largest global middle class market by around 2025, and India as the largest middle class in total buying power by 2030. The USA and Europe will most likely not be the center of worldwide sales of high quality biosimilar products that we will generate over the next five years."