We frequently hear about drug recalls but not so much about the vast majority of drugs that fail after animals testing, but while still in clinical trials. This is one reason why drugs are so expensive and proof of what we say about animal models not being able to predict human response. John Carroll has written an article titled The Top 10 Phase III Failures of 2010 on fiercebiotech.com.
Every Phase III trial represents a throw of the dice, here's a look at some of the top programs that rolled snake eyes in 2010.
You can read the entire article for exactly what the drugs were designed for, why they failed and so forth. Below are some examples:
Dimebon had everything going for it as it entered its Phase III trial for Alzheimer's disease. The bar for success was set low. With patients facing some critical unmet needs, the therapy only needed to demonstrate modest benefits to win an approval. Some analysts believed that even if Phase III wound up far behind the Russian trial that stirred excitement in the drug, Medivation and Pfizer would be well fixed to gin blockbuster revenue from the product. And Medivation could look to 10 years of actual use in Russia as an allergy treatment for solid evidence that the medication is safe.
Pfizer knew the score when it paid a whopping $225 million upfront to gain the license on the drug. And it offered a half billion dollars more in milestones. Alas, when researchers turned in the final data set, Dimebon looked no better than a sugar pill. A very, very expensive sugar pill . . .
Back when Schering-Plough was pushing vicriviroc up the pipeline, CEO Fred Hassan boldly predicted that the HIV therapy was headed for a regulatory filing in early 2010 and would go on to reap as much as $750 million in 2013. And Merck was just as upbeat about its chances when the drug giant bought out Schering-Plough.
So much for bold predictions in the development business. In early 2010 Merck researchers explained that two Phase III trials of vicriviroc, a CCR5 co-receptor antagonist designed to block the virus from penetrating cells, failed to hit the primary endpoint among patients taking a drug cocktail.
A few months later, when the drug failed a study involving treatment-naïve patients, Merck killed the development program.
The news gets worse.
An article in the BBC News by Michelle Roberts states:
Doctors and patients are being misled about the effectiveness of some drugs because negative trial results are not published, experts have warned. Writing in the British Medical Journal, they say that pharmaceutical companies should be forced to publish all data, not just positive findings. The German team give the example of the antidepressant reboxetine, saying publications have failed to show the drug in a true light.
The entire article is worth reading. It discusses: Reboxetine (Edronax), which is used in Europe but not the US; Seroxat and suicide; GSK and Avandia; and how drug companies hide data that makes their products look bad. The article continues:
Dr Beate Wieseler and colleagues carried out their own assessment of reboxetine, looking at the results of 13 trials, including eight previously unpublished trials from the manufacturer Pfizer. They found the drug was no better than a placebo in terms of remission and response rates. And its benefit was inferior when compared with other similar antidepressants. Furthermore, a higher rate of patients had side effects with reboxetine than with placebo. And more stopped taking the drug because of side effects compared with those taking a placebo or a different antidepressant.
The Wieseler article is also worth a read.
The US currently requires that all data from clinical trials be published but the compliance with this is questionable. The EU has no such requirement.
So what does the above have to do with animal testing?
The results from animal testing are not required to be published either. Companies can cherry pick the animal data thus making it appear their product has whatever effect and side effect profile they wish.
An interesting case in point is the current lorcaserin fiasco. The weight loss drug is currently up for approval by the FDA. An expert panel, convened by the FDA voted 9-5 that approval should be withheld. In part, it appears this was based on the fact that lorcaserin induces tumors when injected into rats. This has raised controversy as, according to fiercebiotech.com: “the agency's [FDA’s] own rules allow panelists to disregard data from animal results based on doses 25 times stronger than what's given to humans.” Advocates for lorcaserin (shareholders) are, needless to say, perplexed and unhappy.
So, the FDA (among other regulatory agencies) acknowledges that rat data is not necessarily meaningful for humans but their committees then recommend against approval because of rat data. Truth really is stranger than fiction.
But not new.
Anita O'Connor, formerly of the FDA stated in 1998:
Most of the animal tests we accept have never been validated!! They evolved over the past 20 years and the FDA is comfortable with them.
When asked a question by MP Hancock, then-Home Office Minister Caroline Flint stated on March 31, 2004: “The Home Office has not commissioned or evaluated any formal research on the efficacy of animal experiments.” When asked essentially the same question in April 2004, she replied: "The Home Office has not commissioned or evaluated any formal research on the efficacy of animal experiments and has no plans to do so."
It is hard to prove the value of animal models in the face of logic like that and this kind of fallacious reasoning is costing society money and cures. But as long as vivisection activists can con society into believing that animals are responsible for “virtually every medical breakthrough,” including the MRI machine, and that animal models can predict human response thus making new drugs safe for humans, then the costly and dangerous practice will continue.