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Thought leadership and innovation for the Pharmaceutical Industry

Over the past couple of years there has been much debate about the development of biosimilars and the potential threat that these present for current innovator products.

By Lucy Brake on Feb 25, 2013

More recently however the considerable challenges associated with biosimilar development mean that it is likely it is still some time before biosimilar products can truly become a major player in the healthcare sector.

The challenge of molecular complexity

The key issue, according to Dana Evans, MD, Medical Affairs Payer Support at Genentech, is the difference in complexity of biologics versus traditional chemical molecules and all of the resulting factors: “It’s not just complexity of molecules but also manufacturing, distribution and education. A lot of these features make it very complex to create a biosimilar compared to a chemical drug”.

Biological products are large, complex protein molecules, often with diverse physiological functions. Evans elucidates that the intricacy of these means it is impossible to make an exact copy. “Added to this inherent molecular complexity are complicated manufacturing, formulation and handling processes which are necessary for the production of large, biologically active biological products”. In addition, he says that formulating and manufacturing the finished product is another complex critical step in the process to ensure consistent and reliable delivery to the patient.

Evolving regulatory pathways

The market for safe and effective biosimilars is being established all over the world. These pharmaceuticals have been available in Asia for a number of years, there are already 12 biosimilars approved in the European Union and the United States has set a pathway for an approval framework. The World Health Organization has set guidance for less highly regulated markets to consider biosimilar applications. Most of the emerging pharma markets, including China, India, Brazil and Mexico, have now developed their own regulatory pathway to manage the approval of biosimilars.

“There is considerable time, energy and financial resources to prepare biosimilars for the market and get approval, particularly in the European Union.”

However, Evans believes that what companies are finding based on the European pathway is that it is not a simple process: “There is considerable time, energy and financial resources to prepare biosimilars for the market and get approval, particularly in the European Union, affiliated countries and the United States”. It seems that the time it takes to develop and proceed through the approval pathway is taking a lot longer than industry first thought and this is increasing the risk levels in the process.

The development of biosimilars is a long process that is fraught with risks and costs. So whilst the market is potentially significant, the challenges companies have to overcome are equally great. To help spread the impact of some of these a number of alliances have been formed. Teva has set up a joint venture with Lonza Group to develop biosimilars, Amgen formed a biosimilar partnership with Watson Pharmaceutical Incorporated and Biogen Idec Incorporated teamed up with Samsung Pharmaceutical Industries Limited, to name a few.

But it would appear that now some of the companies involved are now backing off from their original projections for developments. In February 2011, Samsung set up a joint venture with Quintiles TransNational Corporation to start developing biopharmaceuticals. They have now recently “temporarily suspended” clinical trials of a rituximab biosimilar product in Spain and the Czech Republic, but are continuing the trials in the UK, Poland and Hungry. The challenge for these organisations is that the regulatory environment is still evolving. Late 2012 saw the Lonza-Teva joint venture suspended clinical trials for a biosimilar rixtuximab to allow them to evaluate the changes in regulation pathways.

The financial reality

There is significant time and cost involving in creating biosimilars. The tougher regulations, significant clinical trials and comparison trials all add to the mounting costs. 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 US$200 to $300 million, far higher than developing a generic drug. Sandoz estimates a biosimilar would typically take seven to eight years to develop, at a cost of between US$75 and $250 million, with clinical trials that may involve about 500 patients. Compare that to their estimate of eight to ten years for a new drug application, at a cost of US$800 million, including up to 1000 patients in clinical trials. Substantially more cost and time involved than developing a small-molecule generic pharmaceutical.

Sarah Rickwood and Antonio Lervolino from IMS Health prepared a White Paper on the evolving biosimilars landscape. They noted that these drugs bring clear potential in the emerging pharmaceutical or “pharmerging” markets, such as Brazil, India and China. “Biosimilars offer one way of widening access and enabling better value to be obtained from the money spent on healthcare. In some cases they are seen as a key macroeconomic driver of growth, attracting foreign capital by creating manufacturing and R&D centers of excellence”.

A long-term commitment

“They may begin to challenge the patents of the innovator products.”

 

Many in the industry felt that the biosimilar companies may well be close enough to challenge the patents on current innovator products but there still appears to be much work needed before this will happen. “Right now, particularly in the United States, the focus is on the products where the numerous patents are near expiry and where there may be an opportunity to challenge these patents”, remarks Evans. But with it taking longer to get approval this will now far more likely to come after clear patent expiry of "reference" products. “In the future, when the companies have developed the required expertise, they may begin to challenge the patents of the innovator products, but I think that the risk to innovator patents has pretty much gone away for now”.

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Dana Evans will be discussing the effect biosimilars will have on the oncology landscape at the Oncology Market Access & Marketing Summit USA in Boston. Find out more about his presentation, as well as our other speakers, at the official website.