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ISIS Report 04/03/09

‘Biologicals’, Wonder Drugs with Problems

Protein drugs produced by genetic engineering cause adverse events including death more frequently than synthetic chemical drugs; yet they are being produced in transgenic crops grown in open fields Prof. Joe Cummins

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‘Biologicals’ more dangerous than chemicals

‘Biologicals’ are drugs in which the active substance is produced by or extracted from a biological source (in contrast to synthetic chemicals). Biologicals are relatively recent, being for the most part, recombinant proteins produced by genetic engineering.  The first biological was recombinant human insulin produced in recombinant bacteria and commercially approved in 1982.  Currently, there are more than 250 biologicals on the market, including recombinant blood products, monoclonal antibodies and vaccines that have been approved by regulatory agencies in the United States and European Union (EU). Between 2003 and 2006 biologicals  represented 24 percent of all new approvals in the US and 22 percent of new approvals in the EU [1].  Ten biologicals are listed among the top selling ‘blockbuster’ drugs valued at 1 to 3.2 billion dollars in sales. These drugs included treatments for red blood cell disorders, immune system disorders, cancer and insulin analogues [2].

Newly approved drugs are frequently found to cause unexpected problems; but biologicals are incurring problems even more frequently than synthetic chemical drugs. A recent study published in the Journal of the American Medical Association confirms that the biological drugs have provoked significantly more regulatory actions than newly introduced synthetic chemical drugs.  The researchers, based in The Netherlands, followed up a group of biologicals approved in the US and EU between 1995 and 2008, and found that 24 percent of these have prompted safety regulatory actions. New chemical drugs have an 8.5 percent chance of safety warning within ten years of approval, compared to 17 percent for biologics [2].  The regulatory actions included warnings on general disorders and administration site conditions, infections and infestations, immune system disorders and cancers (benign, malignant and unspecified). Adverse events included many serious complications of the drug treatment such as increased mortality, anaphylaxis, cancer, heart failure, stroke, and infections [1].  However, industry representatives implied [2] that the diseases being treated were very serious, and the drugs were efficacious and the adverse events relatively rare. The study concluded [1]: “The nature of safety problems identified after approval for biologicals is often related to the immunomodulatory effect (infections). Because the biologicals first to be approved in a class were more likely to be subjected to regulatory action, close monitoring is recommended.”

FDA blaming the victims rather than the drugs?

A review of the Netherlands study published in Nature Biotechnology acknowledges the significance of the study and the problem of adverse events related to biologicals. The article mentions a caveat to the study’s conclusions added by Sandra Kweder, deputy director of FDA’s office of new drugs at the Center for Drug Evaluation and Research [2]: “Biological therapeutics are more likely to be developed to treat serious illnesses, she points out, and serious illnesses themselves are fertile ground for ‘toxicity’ whether related to the drug or disease, so interpreting data on the drug’s or biological’s risk must take that into account.”  That seems to lay the blame for the adverse outcomes on those being treated rather than the drugs; and looks like an attempt to protect the billion-dollar industry.

The Nature Biotechnology review [2] further comments that industry insiders agree long-term safety monitoring will be crucial for biologics. While the antibody producing company InNexux’s chief scientific officer is reported to have said: “That long-term use may lead to problems I think is a given,” – a suspicion borne out by the latest study - the company’s chairman and ceo Jeff Morhet, finds at least one important consolation: “the study showed that no biological was pulled from the market for safety reasons.”

Lax FDA regulation and a profit-hungry industry

If anything, Morhet’s remark should offer no consolation to those being treated; as it exposes the lack of adequate regulation to protect the public in face of ‘miracle cures’ being offered by an industry whose primary concern is profit. 

Significantly, no one has commented on the 2005 case of the drug Tysabri (natalizumab)  a treatment for multiple sclerosis that was suspended following two deaths of patients from leukoencephalopathy (progressive damage or inflammation of the white matter of the brain) [3]. Nor indeed has anyone mentioned the catastrophic London drug trial of a biological monoclonal antibody drug that left six healthy young volunteers seriously ill [4] (London Drug Trial Catastrophe – Collapse of Science and Ethics, SiS 30).

The Institute of Science in Society (ISIS) has long been critical of the manner in which biological are tested and used in treatment. The adverse event, ‘cytokine storm’ unleashed in the immune system of the volunteers, was not exactly a surprise.  The FDA had issued a long list of warnings on similar monoclonal antibody drugs [5] (Warnings on FDA Approved Monoclonal Antibody Drugs, SiS 30); but that seemed to have been ignored [6] (Post Mortem on the TGN1412 Disaster, SiS 30).

Pharm crops with dangerous biologicals in open field trials put the public at risk

Even more seriously, the secret trials of food crops (pharm crops) in open fields modified with mammalian genes expressing  proteins used to treat human or animal disease continue unabated [7] (Drug Trial Catastrophe & Safety of Secretly Tested Pharm Crops, SiS 30). Pharm crops for vaccines and therapeutic antibodies have been trialed since 2004 and earlier [8] (Pharm Crops for Vaccines and Therapeutic Antibodies, SiS 24). Antibodies are produced in tobacco plants [9] (Antibodies from Hybrid GM Tobacco Plants, SiS 35) and in maize [10] (Transgenic Maize with Monoclonal Antibodies Grown in France, SiS 35). Biologicals are well known to have severe side effects on patients and on healthy people. There is no justification for exposing the unsuspecting public to these drugs produced in pharm crops grown in open fields.


1. Giezen TJ, Mantel-Teeuwisse AK, Straus SM, Schellekens H, Leufkens HG, Egberts AC. Safety-related regulatory actions for biologicals approved in the United States and the European Union. JAMA. 2008, 300(16), 1887-96.

2. King J. JAMA casts cloud over biologic safety. Nature Biotechnology 2009, 27,11-12.

3. FDA Public Health Advisory Suspendec Marketing of Tysabri (natalizumab) 2005 updated 2007

4. Ho M-W and Cummins J. London drug scandal catastrophe, collapse of science and ethics Science in Society 30, 41-43.  2006.

5. Cummins J. Warning on FDA approved monoclonal antibody drugs Science in Science in Society 30, 46-47.  2006.

6. Saunders PT. Post mortem on the TGN1412 disaster. Science in Society 30, 44-45+47,. 2006.

7. Cummins J and Ho M-W. Drug trial catastrophe & safety of secretlytested pharm crops Science in Society 30, 50, 2006.

8. Cummins J. Pharm crops for vaccines and therapeutic antibodies Science in Society 24, 22-23, 2004.

9. Cummins J and Ho M-W. Antibodies from hybrid GM tobacco plants. Science in Society 35, 51, 2007.

10.  Cummins J, Ho M-W and Saunders PT. Transgenic maize with monoclonal antibodies grown in France Science in Society 31, 4, 2006.

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