Posted by Julia Adam | Under Biosimilars, Monoclonal antibodies, Supply chain
Tuesday May 8, 2012
By Patti Seymour (pseymour
bptc
com)
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.
Posted by Julia Adam | Under Cell therapy, Conference announcement
Monday May 7, 2012
Posted by Julia Adam | Under Biosimilars, Monoclonal antibodies, Regulatory
Wednesday May 2, 2012
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?
Posted by Julia Adam | Under Conference announcement, Manufacturing technology, Process development, Product Development, Quality, Regulatory
Tuesday Apr 24, 2012
Posted by Julia Adam | Under bioPULSE, Manufacturing capacity, Process Analytical Technology, Quality by design, Vaccines
Thursday Mar 29, 2012
By Patricia Seymour
The results from BPTC’s bioPULSE survey on vaccine manufacturing highlight industry predictions for new technologies and risks involved in vaccine manufacturing.
The two most prevalent technological advances expected to have the greatest impact on vaccine manufacturing in the next 5 years are flexible manufacturing and novel delivery systems. Respondents indicated that microbial fermentation, followed closely by mammalian cell culture, are the two technologies best suited to develop new or pandemic vaccines. Compared with mammalian cell culture, microbial fermentation has the advantage of relatively short production cycles and low cost. However, several new, highly effective vaccines are being developed using mammalian cell culture to overcome limitations of traditional egg-based production systems. Application of Quality by Design (QbD) and Process Analytical Technologies (PAT) are also rapidly gaining acceptance in all aspects of biomanufacturing, according to a majority (73%) of respondents. Formulation development (44%) and downstream purification (44%) would benefit far greater than upstream processes (12%) from application of QbD according to respondents. (Share your thoughts on QbD in our current bioPULSE survey!)
Nearly half think access to manufacturing capacity is the greatest risk factor in meeting global demand for vaccines. As the patients in emerging markets are able to access these lifesaving medicines more routinely, vaccine use is expected to increase significantly in the coming years. Recognizing the growing need for new vaccines, two-thirds of the survey respondents indicated that they are either currently developing or plan to develop vaccines. The overall vaccine market has seen growth rates of up to 10% in the past few years fueled by wider use of current vaccines and introduction of new vaccine therapies. Compared to the 5% growth for the overall pharmaceutical industry, the vaccine market should continue to be a bright spot.
One third of respondents are planning to increase the use of disposable technologies in order to allow manufacturing facilities to be rapidly and cost effectively established locally in emerging markets. Only small percentages (4%) of companies are out-licensing vaccine products to companies in emerging markets. This low percentage is most likely due to concerns about protection of intellectual property and manufacturing know-how.
To ensure that new vaccines can reach the patients who need them, it is important for global regulatory agencies not to set divergent requirements for the approval of vaccines in their territories, which ultimately could increase the cost and time to commercialize vaccines, or worse, disincentivize manufacturers from marketing their vaccines in certain territories. It is not surprising that the majority, 64%, of survey respondents indicated that governments should fund the research and development of pandemic vaccines. This may be controversial in some circles, but without government support, most not-for-profits could not provide the funding needed to bring a vaccine completely through its development cycle, and for-profit companies have little or no incentive to develop pandemic vaccines if there is not a guaranteed market (i.e., governments).
The objective of all bioPULSETM surveys is to obtain relevant and focused feedback on topics of interest to the biologics manufacturing community. The web-based surveys are quick, short, and rewarding (everyone who participates will be emailed a summary and analysis of the aggregate results), so we hope you will join the growing bioPULSE community and contribute your insight.
