BioProcess Blog |

By Patti Seymour  (pseymourbptccom)  

Biopharmaceutical products will dominate the list of top ten best selling drugs in 2012. Abbott Laboratories’ arthritis drug Humira^® (adalimumab) is forecasted to become the world’s top selling drug in 2012, followed closely by Johnson & Johnson’s Remicade^® (infliximab) and Amgen’s Enbrel^® (etanercept). Roche is also a member of this exclusive group, with three anti-cancer drugs, Rituxan^® (rituximab), Avastin^® (bevacizumab) and Herceptin^® (trastuzumab) ranked in the top ten. As described in a recent BPTC report, seven biopharmaceutical blockbusters had sales in excess of $5 billion per year in 2010, with total biopharmaceutical sales exceeding $100 billion. According to the IMS Institute for Healthcare Informatics, global biopharmaceutical spending is forecasted to grow to $200 billion by 2015. This market growth is being fueled by the approval of new products and expansion of therapeutic indications from existing products – Humira just received approval for its seventh indication and Remicade has 16 approved indications! However, the blockbuster status of these drugs is being threatened on numerous fronts.

Several of these top selling products will lose patent protection in the next few years, and biosimilar developers have been ramping up to take advantage of these huge market opportunities. By the middle of this decade, spending on biosimilars is expected to grow to $2 billion from $311 million in 2010. Biopharm companies aren’t ready to cede market share to potential biosimilar competitors, though. Roche recently announced plans to cut the price of Herceptin and MabThera (rituximab) in India and rename them in an effort to gain market share and avoid competition from biosimilars in that country. Roche hopes that the lower prices will increase usage rates in India "at least several-fold higher" than current levels, according to Tuygan Goeker, head of Middle East and Asian markets at Roche. The new product names should create an obstacle to companies seeking to divert the Indian products and resell them at a significant profit in other markets, but this is no guarantee that the drugs won’t be diverted to other markets, as Roche knows all too well.

Roche is dealing with the fall-out from counterfeit Avastin from Turkey making its way into the United States supply chain. According to World Health Organization, less than 1 percent of medicines available in the developed world are likely to be counterfeit. While the threat of counterfeit medicines entering the supply chain in the United States is lower than elsewhere, the temptation for doctors to seek cheaper versions of high cost drugs is increasing, especially for biopharmaceuticals, leading to potentially more counterfeited high value drugs finding their way into the US pharmaceutical supply chain. Doctors may unknowingly purchase inferior or unsafe drugs, as was the case in the most recent Avastin counterfeit incident involving “product” that contained no active ingredient.

Another threat facing these blockbuster products is the potential issuance of compulsory licenses to generic manufacturers as evidenced by the Natco Pharma case. In March, Indian drug company, Natco Pharma, was authorized by the Indian government to make and sell a generic version of Bayer’s patented cancer drug, Nexavar. Roche’s plan to rebrand Herceptin and MabThera in India is considered by many a preemptive move to avoid being compelled under Indian law to allow generic drug makers to produce less-expensive versions of these drugs, a fate that Bayer wasn’t able to avoid. In response to India’s issuance of a compulsory license to Natco Pharma for Nexavar, PhRMA President and CEO John Castellani said, “If countries begin to routinely use compulsory licenses, we could see a ‘race to the bottom’ in which governments in the developing world walk away from their responsibility to support research and innovation in public health. In the absence of the investment made by our members, and the resulting research and development, there would be no generic medicines for the world’s patients.”

While companies are taking proactive measures to protect top selling biopharmaceuticals from biosimilar competition, effective annulment of patent protection through compulsory licensing initiatives coupled with the increased counterfeiting of high value products in emerging markets could pose more insidious threats to biopharmaceutical product companies than the emergence of biosimilars.

By Patti Seymour  (pseymourbptccom)  

Not surprisingly, a biosimilar version of Remicade^® (infliximab) is the first regulatory application for a biosimilar monoclonal antibody (mAb) submitted to the EMA this month. Remicade^®, marketed in the EU by Janssen Biotech (a subsidiary of Johnson and Johnson), is a mAb against tumor necrosis factor (TNF) alpha and is approved for a whopping 16 indications. While the name of the company submitting the application wasn’t disclosed by the EMA, it is widely acknowledged to be Celltrion’s submission.

Celltrion’s infliximab clinical trials were conducted with a total of 874 rheumatoid arthritis patients at 100 sites in 19 different countries throughout 2010 and 2011. It is unknown at this point if Celltrion is requesting approval for other indications in addition to rheumatoid arthritis as EMA Guidance allows for extrapolation of clinical efficacy and safety data to other indications for which the reference mAb has been approved. It is not necessary that these indications be specifically studied during the clinical development of the biosimilar as long as there is evidence of overall biosimilarity provided by the comparability exercise with adequate justification.

Approval from the EMA to extrapolate to multiple indications will be important for Celltrion to capture a meaningful portion of the $21 billion TNF-a antagonist market. While Remicade is forecasted to be one of the top three selling drugs in 2012, it was also one of the earliest mAbs to receive regulatory approval, and as a chimeric mAb (containing both human and murine sequences), it has some safety limitations associated with immunogenicity. Over the past decade, these older products are being supplanted with newer, humanized or fully human mAb versions such as Humira^®. While biosimilar competition remains a concern, the verdict is still out as to whether Remicade’s $8 billion market is more likely to be cannibalized by biosimilars or by biobetter and next generation products, such as Janssen’s own Simponi product.

Now it is a waiting game for Celltrion as the earliest patents for Remicade do not expire until 2014 in the EU. However, Celltrion isn’t taking a ‘sit and wait’ approach – the company is preparing to file for Korean Food and Drug Administration approval this year. After that, the company plans to register their biosimilar infliximab product in emerging markets in Asia and Central/South America, where Remicade does not have patent protection.

While Celltrion was the first to file for approval of a biosimilar mAb, there are sure to be many more companies submitting biosimilar mAb applications in the near future. The first-mover advantage could be short-lived for Celltrion as more companies seek biosimilar market authorization, and branded products continue their strong market performance. This is further compounded by the fact that overall adoption of the early biosimilar products in Europe has not been as strong as anticipated or hoped even with price discounts up to 40% for some products from the branded product’s price. Samsung, clearly positioning itself to be a dominant player in the biosimilar market, predicts it will be a stronger overall competitor by selling its biosimilar portfolio at up to 50% off the innovator drug price. We believe that such price drops are achievable and will lead to significant gains in market share by Samsung and other biosimilar companies able to actually deliver on this promise. However, before steep price discounts can become a reality, products must be approved. So the questions remain – What hurdles will Celltrion face in the approval process? How easily will they be able to access other indications after approval? And of course, what kind of market penetration will Celltrion’s infliximab really achieve?

by Howard Levine  (hlevinebptccom)  

With the continued growth in sales and number of products, the biopharmaceutical industry is rapidly becoming the driver for the overall pharmaceutical industry. In this fully documented and referenced report we draw from our proprietary Biopharmaceutical Product database to analyze the continued growth of biopharmaceutical sales. We review the production methods used for these products and analyze the impact of those produced in mammalian cell culture on global manufacturing capacity. Despite the continued growth in sales of biopharmaceutical products and the associated requirement for increasing mammalian cell culture capacity to meet this market demand, we find that overall capacity utilization rates have remained low and forecast that average industry-wide capacity utilization will increase approximately 50% from 2011 to 2016 as construction of new capacity slows and more products reach the market.

The impact of this increasing utilization rate on biomanufacturing capacity and the current concentration of this capacity in a small number of companies may limit some companies’ ability to access capacity in a timely manner. While the five product companies controlling the majority of cell culture manufacturing capacity have more than enough capacity to accommodate their anticipated future needs and keep their own utilization rates low, many of the remaining companies, which either have smaller-scale manufacturing capacity or are relying on CMOs, may find a need for additional capacity by 2016 suggesting that CMOs and smaller biopharmaceutical companies may announce the installation of new capacity in the coming years.

The 150-page State of Mammalian Cell Culture Biomanufacturing report provides a comprehensive analysis of the current and future supply and demand for mammalian cell culture capacity, including the geographic distribution of manufacturing capacity, the impact of facility utilization rates on overall capacity requirements, and the influence of emerging technologies on manufacturing facility design and utilization. With detailed figures, graphs, and tables highlighting including a comprehensive list of sales data and bulk product requirements for all biopharmaceutical products produced in mammalian cell culture currently on the market, Unlike other qualitative surveys or unreferenced articles on biomanufacturing, The State of Mammalian Cell Culture Biomanufacturing provides detailed, data-driven insight into the mammalian cell culture manufacturing market to inform senior executives and program managers with the essential and timely information needed to fully understand the mammalian cell culture manufacturing landscape and to stay competitive.

Dr. Sheila Magil  (smagilbptccom)  , Senior Consultant, will join Dr. Gurmil Gendeh of Thermo Fisher, and Dr. Nesredin Mussa of Lonza Biologics to present a live webinar titled Speeding Up Monoclonal Antibody Screening and Characterization on August 31, 2011.  The webinar will provide an overview of regulatory challenges and standards for characterizing MAbs and discuss new developments in analytical methods to increase performance, throughput, and productivity of MAb screening and characterization. Click here to register for this free webinar.

Susan Dana Jones will be representing BPTC at this year’s ESACT conference in Vienna, Austria, May 15-18. To meet with Dr. Jones at the conference, click here.