Biologics Have High Rate Of Safety Risks: Study
4 CommentsBy Ed Silverman // October 21st, 2008 // 10:37 am
Approximately one in four biologics approved since 1995 in the US and Europe have had at least one safety-related regulatory action issued for them 10 years after their approval, including about 11 percent receiving a Black Box warning, according to a study in the Journal of the American Medical Association.
The new study is the first comprehensive examination of biologics, and among those cited were the Humira and Remicade arthritis treatments; the Rituxan and Erbitux cancer meds, and the Natrecor drug for heart failure. Most warnings, by the way, came within five years after approval (here is the study).
“Between 2003 and 2006, biologicals represented 24 percent and 22 percent of all new chemical entities approved by the US and EU regulatory authorities, respectively,” the authors write in JAMA. “Biologicals are a relatively new class of medicines that carry specific risks (such as immunogenicity). However, limited information is available on the nature and timing of safety problems with their use that were identified after approval.”
A total of 174 biologics obtained approval during the study period, including 136 approved in the US and 105 in the EU, of which 67 obtained approval in both regions during this time. Between January 1995 and June 2008, 82 safety-related regulatory actions were issued for 41 of the 174 biologicals, or 23.6 percent. These included 46 written communications to health care professionals in the US, 17 in the European Union, and 19 black box warnings. None were withdrawn due to safety reasons. The probability of a biologic requiring its first regulatory action was 14 percent three years after approval and 29 percent 10 after approval.
The results are a concern, and they underscore the need for closer scrutiny of drugs after their approval, according to lead author Thijs Giezen of the University of Utrecht in The Netherlands, but adds the study is also reassuring because most problems showed up relatively soon after the drugs became available, which minimized the potential for widespread harm. “If most issues are discovered within the first few years, then the system is working,” Giezen tells the Associated Press.
Many biologs have advantages over conventional medicine, but the study shows their risks need to also be considered, according to Tom Moore at the Institute for Safe Medication Practices. For example, he cites to the AP non-steroid arthritis meds including ibuprofen can reduce pain by decreasing inflammation, but they can cause stomach bleeding.
“My message to patients is that these biological products often can treat very difficult to treat diseases but may have very substantial risks and that you need to take extra care to educate yourself as to what those risks might be,” Moore tells the AP.
As Charles Bennett, a Northwestern University drug safety expert, who was not involved in the research, tells the AP, biologics are genetically engineered and, typically, resemble naturally occurring proteins. As a result, many docs have assumed they were safer than traditional chemical-based meds, but he says the study shows that’s not necessarily true.
Still, he says it’s unreasonable to think that biologic safety issues should have been discovered before they were marketed, because approval is based on relatively small studies with patients who generally are healthier than those in the general population. It often takes real-world experience for side effects to appear, he tells the AP.
Dan A.
Biopharmaceuticals: Potential Benefit Public Health… Eventually
Biopharmaceuticals, also known to be in the red biotechnology classification, are specialty therapeutic agents created differently than other typical synthetic pharmaceuticals, and therefore are have a unique molecular complexity that are designed for serious illnesses such as anemia or multiple sclerosis. Unlike typical drugs, biopharmaceuticals are large complex protein molecules developed utilizing living organisms, such as certain cell. A host cell is manipulated and is inserted into a cell line where it is cultured to produce the desired protein by the manufacturer. This is a common method of production of biopharmaceuticals.
Because of their uniqueness and exclusivity, they are very expensive- costing thousands a month for the payers, as the manufacturer of such therapies spend over a billion dollars bringing such a biologic to market. The incentive for the manufacturer is complete exclusivity, as follow on biosimiliars are not authorized as of yet in the United States, yet are in Europe on a case by case basis. Generic biologics are not possible, as duplication cannot be developed, as all biologics are created with some degree of difference. Also, only about a third of biologic agents make it to market after initiating the development of a particular agent
Biologic medications began to be used primarily in the 1980s and now this new industry presently make close to80 billion a year- with about 15 percent growth in this market annually, and this is twice the growth of the pharmacetuical industry. With anemia patients, oncology and dialysis clinics are targets for such meds in this category, as anemia is associated with their treatment and conditions for such diseases. Venture capitalists usually fund the manufacturers of such products produced by new and small manufacturers. Presently, Genentech and Amgen have the largest share of this market.
Yet, some claim that biopharmaceutical products benefit patients to only a certain degree, as they do in fact extend the life of such patients, such as those on chemotherapy or dialysis, but by only a few months. So the high cost of these meds is questionable and has been debated by others. But again, no substitutes for these products are allowed in the United States, which may explain the very high cost of most biologics. Also, and to some degree, the efficacy of these biologic agents have also been questioned as well in other treatment aspects aside from life extension.
Then there is the issue of fraud with kickbacks and overuse of some of the biopharmaceutical meds used to treat anemia in dialysis clinics in particular. On a few occasions, doctors and clinics have been penalized for overusing the meds and for kickbacks in the form of discounts of the manufacturers. Ironically, the dialysis process was never patented, yet the many centers that exist have proven to be very profitable, more for some than others. An example is the situations where dialysis doctors, called nephrologists, have been accused of over-dosing patients with biologic meds to increase their income through their discount arrangement through the manufacturer of such meds, such as those biologics for anemia, and this arrangement is being investigated by regulators and encouraged by the representatives of such meds.
Presently, there are many that approach the FDA to aggressively insist that follow on biologics be allowed into the market for the benefit of these critically ill patients, and this would be of great benefit for such patients, and this can be done, as far as judging such an agent in molecular and biologic terms. And their efforts have been somewhat successful, as the follow on equivalents of biopharmaceuticals, called biosimilars, could be manufactured and available within the next few years if authorized by this industry’s regulator, which is the Public Health Services Act, a subsidiary of the FDA. However, this situation of biosimiliar delays illustrates one of many flaws in the U.S. Health Care System- when the sickest have to complicate their illnesses by possible financial stress, such as the case with biologic agents. Relief is needed, and should be demanded by the public. After all, why be so sick, and then be financially burdened? One solution or suggestion is to either lower the cost of these types of drugs, or allow biosimiliar forms to enter the market faster than what the situation is presently. Recently as well, synthetic biotechnology is speculated to be present in the future.
“A little learning is a dangerous thing.” —- Alexander Pope
Dan Abshear
Jane Chin
When I was working in oncology in early 2000’s, targeted therapies were the buzz, and many oncs preferred working with targeted agents and biologics. One of the marketing messages appeared to be the “safety profile” of these biologics.
Those scientists who have studied the complexity of signal transduction and the ways cells are “wired” not just within itself but as part of a cellular organization know that disrupting factor pathways have wide reaching consequences beyond the grossest observable interruption proximal to that pathway.
It would only be a matter of time that our ignorance about the wide reaching consequences manifest themselves as “side effects”, and unfortunately, the management of these side effects may not be as simple.
Anne PME
There are other variables that add to the risk of biologics:
1. They tend to be at higher risk of tampering because they are A. difficult to produce and B. expensive. Because te patient population who takes them is usually frail to begin with and on multiple drugs, when the patient is harmed by an unfit dispense, product tampering is often NEVER SUSPECTED, and proof of harm is more complicated.
2.They are often administered as IM or IV drugs. The administration process is more complicated, requires more training and equipment, and carries more risk (as we have seen in Wyeth vs. Levine)than other routes of admin.
3. The patient population that takes them is usually more physically vulnerable, but because of the seriousness of their medical condition, their treatment options are often riskier and they may be willing to accept higher risk
4.These drugs often require specialized (and $$$) S & H and have shorter shelf life.
David
> Between January 1995 and June 2008… None were withdrawn due to safety reasons
Trasylol (biologic) was withdrawn in 5/08.