Disappointing Biotech (response)
Pharma’s Cutting Edge
Vol. 3 Number 10 - October 2005
Disappointing Biotech (response)
The following is a letter I wrote to the Editors of the British Medical Jorunal in response to the recent article by Joppi et al entitled: “Disappointing Biotech.” This is a slightly modified version of the original, full-length letter. A much condensed version, which is also toned down in its criticism, will be published next week in the journal. I give the BMJ credit for at least trying to inject some balance into their almost constant criticism of the industry. In the current issue a couple of academics argue that the pharma industry invents false arguments to justify higher prices for medicine in the US. I’ll read and critique that one some other time.
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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 by the authors for 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 innovation classification (disappointment #2). The largest category of drugs (24) were classified as “copycat or me too products”–pejorative terms that effectively cast prejudicial doubt upon a drug’s value. I am 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 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 misclassified.
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 guideline 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.
