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Disappointing biotech critique
- Fredric J Cohen (18 October 2005)
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Biotech not disappointing!
- Johan Vanhemelrijck (24 November 2005)
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A comment to "Disappointing Biotech"
- Sergio Chimenti (14 December 2005)
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Fredric J Cohen, President Pharma Growth Strategies LLC, 3331 Street Rd., Suite 140, Bensalem, PA 19020 USA
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The BMJ continues its apparent new-found tradition of pharma/biotech industry bashing with the publication of Joppi et al's disappointing biotech critique ("Disappointing biotech" BMJ 2005; 331: 895-897). Readers should be disappointed by the article's lack of balance and by BMJ's decision to publish it without an accompanying counterpoint. The paper begins with the misleading premise that biotechnology promised "cheaper" medicines: "[T]hey are...cheaper to make thanks to potential large scale production." Putting aside the lack of a definition of a biotech product, "they are cheaper to make" than what? Small molecules? Surely the authors recognize that the production and distribution of large molecules, particularly monoclonal antibodies, can be extraordinarily expensive, much more so than "traditional" medicines. The authors have set their story on a faulty foundation, hoping to convince readers that they should be disappointed in their expensive new medicines. Instead, I am already disappointed by the critique and I've not yet read past the second sentence. The authors identified 61 active substances approved in Europe from 1995 to 2003 and categorized them according to their own innvoation classification (disappointment #2). The majority of drugs (24) were classified as "copycat or me too products"--perjorative terms that effectively cast prejudicial doubt upon a drug's value. I am very familiar with one of the drugs on the "copycat" list, teriparatide (rhPTH1 -34, Forteo, Eli Lilly and Company), a treatment for osteoporosis. I assisted with its development while I was employed at Lilly. Teriparatide was the first and remains the only drug in its class to be approved for osteoporosis. It was also the first bone-anabolic agent ever widely approved in Europe. Many experts have characterized the drug as an extremely important addition to the treatment options for osteoporosis, especially for those with advanced disease who are mostly likely to suffer debilitating consequences. Yet the authors denigrate the drug by classifying it as a "copycat." If such an obviously pioneering innovation as teriparatide may be classified by Joppi et al as a copycat, I have to suspect that other drugs on this list are also mis-classified. The bulk of the article's text is devoted to an examination of the studies used to support approval of the 15 self-selected drugs classified as "innovative." The authors criticize some of the development programs as non-rigorous and imply that "commercial priorities often come before the sound development of drugs." Their criticism strikes me as either profoundly naive or ignorant of the realities of modern drug development and sales. More likely, given their experience in the drug regulatory environment, the authors have simply chosen to obfuscate the realities to further their agenda (which is, I presume, more government regulation of drug innovation). Over a quarter of the 15 "innovative" drugs identified were for orphan diseases, which by definition affect very small populations with high unmet need. The authors criticize the use of placebo-controlled studies using "soft" endpoints for orphan drugs. A placebo-controlled study is often the best way to determine the effect of a drug on a disease endpoint (see ICH guidline E10 for a complete discussion). In a disease without established treatments, it is almost always the preferred study design. As for "soft" endpoints, I assume the authors refer to non- survival endpoints. By use of the term soft, they again attempt to prejudice the reader by implying that the endpoints were invalid or irrelevant. This is unlikely to be the case. As the authors undoubtedly well know, regulatory authorities do not accept just any endpoint as a basis for approval. The primary endpoint must be relevant to both the disease and to the purported action of the drug. Always of relevance is the influence of chosen endpoint(s) on the health of the subjects being studied. When studying an orphan drug it is in the interests of all involved to find an effective medicine as quickly as possible. As no effective therapies yet exist, a placebo-controlled study with a primary endpoint that will result in the quickest route to determining an effect of the drug that could theoretically tip the benefit:risk balance favorably must be chosen. In other words, the four orphan drugs identified in this paper were likely developed appropriately. The authors also decry the lack of active comparator studies and randomized studies of five other "innovative" drugs. What they don't mention in the article are the regulatory views of those development programs. Instead, they imply that commercial considerations took precedence over good science in these cases. By this implication, the authors seek to leave the reader with the impression that commercial priorities and scientific priorities are set in opposition to one another. The truth is that the two are inextricably linked. Good science must drive drug development planning, but it must be informed by commercial realities if it is to be relevant to the end user, that is, the patient. Furthermore, as I have argued elsewhere, medical innovation is driven and sustained by profit potential, and profit potential can be realized only through the application of commercial planning during development. There is nothing wrong with designing drug development programs so that they succeed in both the regulatory and commercial realms. Indeed, the continued availability of innovative medicines, including all 61 innovative medicines identified by the authors, depends on such success. Competing interests: None declared |
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Johan Vanhemelrijck, Secretary General of EuropaBio, the European Bioindustry association 1040 Brussels, Belgium
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Education and debate Disappointing biotech EDITOR – The authors of this article have analyzed the existing situation in healthcare biotech in Europe, which unfortunately fails to represent the complexity of the development and registration processes of therapies derived from biotechnology. Other authors, such as Janice Reichert at Tufts University in Boston, US, have published about the available data in the US, and concluded rather different and more positive findings(1). The European Union’s Lisbon agenda and goals on EU competitiveness require a positive attitude towards one of its main pillars, which is biotechnology. An overview of the value that biotechnology products has brought to the treatments of previously unmet and critical medical needs would have been of great value, especially since they include treatments which are possible for the first time in human history. Such an approach may have led to a better understanding of the increase in costs of the regulatory framework. It may also have changed the perception that there are only costs, since patients, treated with the innovative products, take an active role in society again, and create added value (2). The highly innovative nature of biotechnology products has required an innovative approach from legislators. European legislators and regulators seek to create appropriate rules for biotech products, with an eye for risk management and the innovative nature of the products. Initially, procedures for granting approval in Europe under exceptional circumstances (3) were designed to increase the time to approval for important innovations. Biotechnology products often met these criteria, so the system was often applied to them. However, the European Medicines Evaluation Agency, EMEA, has made post-approval studies a stringent requirement for products approved under these conditions. Examining the evidence only at the time of marketing authorization fails to take into account these facts. Although innovation can be applied to increase safety or economic convenience (e.g. formulation, drug delivery, potency etc…), it needs to be defined from a patient’s viewpoint, not from a purely scientific stand. The availability of biotechnology and related tools has led to a worldwide increase in R&D, based on a desire for more and better information on the genetic and biological basis of disease. The pathophysiology of many diseases is now much better understood, and has allowed the discovery and development of highly selective new therapies, many of which are still under final development. The application of this new knowledge and technology to development and manufacturing has also led to increasing costs for a novel medicine. Between 1995 and 2000 the estimated cost from discovery to launch of one successful, “traditional” drug was 1.1 billion US dollars. According to the same source, that price has gone up to 1.7 billion US dollars between 2000 and 2002 (4). Studies by Tufts University give costs of 840 million $ per new medicine. Whatever the average cost is, it is clear that it is very high, and that with one success, there are also many failures. In biotech, many small companies with a failed product simply disappear, and with them the costs borne by the investors. Finally, access to innovative therapies, including those derived from biotech, is not an issue of pricing, but rather one of affordability and effectiveness. This is causing a paradigm shift in healthcare systems worldwide with a broader involvement and commitment of policy makers, governments and health authorities, together with insurers, payers and manufacturers to work towards a patient-centered healthcare system. Such system will remain affordable by scrutinizing development costs, but also by weeding out inefficiencies in healthcare systems and stopping reimbursement of ineffective therapies. A recent quote by Sir Michael D. Rawlins, Chair of the UK’s NICE (5), on promoting health by enhancing innovation comes to mind: “Our capacity to meet unmet medical need should be great. We are, though, in danger of jeopardizing this potential if we do not make every attempt to reduce the cost of drug development. It will not be easy; nor will it be uncontroversial. There will be political, social and legal challenges to be addressed. But if we do not work towards this goal, we will fail future patients, their families and society as a whole.(6)” Jo Vanhemelrijck, Secretary General, EuropaBio (1) Reichert JM, Rosenwig CJ, Faden LB, Dewitz MC. Monoclonal antibody successes in the clinic. Nature Biotechnology 23(9):1073-1078 (2005) Pavlou AK, Reichert JM. Recombinant protein therapeutics—success rates, market trends and values to 2010. Nature Biotechnology 22(12):1513- 1519 (2004) Reichert JM. Biopharmaceutical approvals in the US. Regulatory Affairs Journal Pharma 15(7): 491-497 (2004) (2) Bioimpact study, www.bioimpact.org (March 2005) (3) Part 4 G of the Annex to Directive 75/318/EEC (4) Windhover’s In Vivo: The Business & Medicine Report, Bain Drug Economics Model, 2003 FDA : Challenge and Opportunity on the Critical Path to New Medical Products, March 2004 (5) National Institute for Health & Clinical Excellence, the independent organisation in the UK responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health. (6) Source: Sir Michael D. Rawlins: « Cutting the cost of drug development? » - Nature Publishing Group April 2004 Competing interests: None declared |
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Sergio Chimenti, chairman and professor Department of Dermatology, University of Rome
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To the Editor of British Medical Journal (BMJ) I would like to comment the article appeared on BMJ, on the 15th of October 2005, titled “Disappointing Biotech”, from the group directed by dr. Garattini (BMJ 2005;331:895-897). Being a dermatologist I was surprised to see etanercept included among the “me too” substances. If we consider biologics, etanercept is the only one to be and to act as a receptor rather than an antibody, like all the other biologics do. Being a receptor, etanercept does not induce the formation of neutralizing self-antibodies able to reduce the long-term efficacy of the treatment. Moreover, what is new and peculiar about etanercept is the possibility of treating psoriatic patients continuously or with intermittent use. Retreatment, as has been shown in a recent paper, results in the same efficacy of the initial treatment, it is not associated with rebound phenomena and, most of all, shows the same high tolerability profile as that in the initial treatment. I disagree with the authors when they say: “the promise of good tolerability of biotechnology substances has not been met”, I would rather highlight the improvement in quality of life, which is, for the psoriatic patient one of the primary issues and remains for the dermatologist one of the main endpoints to consider in assessing the regimen of treatment. Sergio Chimenti, MD Professor and Chairman,
Department of Dermatology,
University of Rome "Tor Vergata",
PTV - Policlinico di Tor Vergata,
Viale Oxford 81 - 00133 Rome, Italy
Competing interests: Sergio Chimenti is consultant for Dompè in 2005 |
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