SHAC - HLS Customer Drug Disasters

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HLS proudly tell us of their links with some of the biggest biotech companies in the world. We have long argued that HLS’s defence of unscientific animal tests is linked to these companies releasing drugs which go on to kill people. Unfortunately for patients, there are many examples of HLS customers harming people in this way.

Over recent months, the disasters caused by HLS customers have continued.

HLS customer AstraZeneca manufacture Crestor. Reports in the summer of 2005 linked Crestor with double the rate of side effect rates of comparable drugs, and six times the rate of some similar treatments. Some patients died.[1]

In February 2006 AZ’s problems continued as it’s blood thinner Exanta was found to cause liver damage they were forced to withdraw it.[2] It was unclear whether the ‘rapid onset’ of liver disease was linked to deaths in clinical trials.

Another customer is Serono, who were implicated last summer when they admitted that Multiple Sclerosis drug Novantrone was dangerous.[3] “Diminished cardiac function may occur early on in the treatment with Novantrone” they admitted, although only relabelled the drug and continued to sell it. Experts spotted the problem – animal testing, and concluded. 'Experimental allergic encephalomyelitis is not a suitable animal model for testing treatments for multiple sclerosis and it is time to explore alternative experimental and therapeutic approaches.'[4]. An analyst said “The drug is burdensome already because it has a large side effect catalog"[5]
The drug was licenced from Amgen, who are also a HLS customer.[6]

Pfizer were back in the news again. Bextra (a painkiller) narrowly escaped being withdrawn in America early in 2005, then later was withdrawn in April following more discoveries.[7] Patients were developing a rare but life threatening skin diseases.[8]
In early 2006 their painkiller Celebrex was linked to a more than doubled increase in heart attack risks.[9]
Pfizer were also linked to eleven deaths in a clinical trial for an Alzheimer’s treatment in March 2006.[10] Among patients taking a placebo, the death rate was zero. Pfizer were only marketing the drug: it was manufactured by Esai, another HLS customer.
And in May 2005, their most famous drug Viagra hit the news again, this time linked to blindness. Reports of temporary and permanent blindness have been filed by patients who took the drug, which alters blood supply to the retina.[11]

Another suspicious clinical trial was reported in summer 2005 by a company long-suspected to be a HLS customer – Eli Lilly. A 19 year old drug trial participant was found hanging dead after taking an anti-depressant. Although these drugs have been linked by adverse drug reaction (ADR) reports and by expert analysis to suicide, Lilly denied the link in the case of Tracy Johnson.[12] Her death while testing Cymbalta, a similar drug to Prozac, caused concern as the drug is already on sale in Europe including the UK under the name Yentreve. The American drug regulators the FDA agreed that the drug was not linked to Traci’s death, although a spokesman for Traci’s family said the FDA never spoke to them, and the drug was also linked to another 13 suicides and 41 deaths. It’s worth considering that stress urinary incontinence is hard to model in a beagle.

Another Eli Lilly drug, Strattera, was criticised by regulators after being linked to suicidal thoughts and other behavioural problems in teenagers.[13] Eli Lilly also make Prozac, which was revealed in later 2005 to be the cause of a greater risk of birth defects for mothers taking it – as is Seroxat (GlaxoSmithkline, another HLS customer).[14]

There remains no animal model is Parkinson’s Disease. Even if there was, the ADR caused by Mirapex would have been impossible to detect. The drug, manufactured by HLS customer Boehringer-Ingelheim Pharmaceuticals Inc. was found to cause a desperate urge to take part in gambling. A retired government intelligence worker told how he lost thousands before finding other patients had similar experiences on an internet site. A lawyer representing patients said he had spoken to 200 Mirapex patients who had developed compulsive addictions including gambling, shopping and sex.[15]

GlaxoSmithkline were implicated with deaths among patients when their asthma treatments Advair and Serevent were examined. The active ingredient, salmeterol, was linked to inducing asthma attacks, which were sometimes fatal. A clinical trial found death rates were over nine times higher in the Serevent group compared with those receiving a placebo.[16] Forbes magazine claimed 4,000 people die each year as a result of taking Advair.[17] In late 2005 Agenerase (amprenavir) had a warning imposed by a regulator after more unforeseen ADRs.[18]

At the same time similar questions were being asked about a similar drug to Advair.[19] Foradil is made by Novartis, also a HLS customer. They were also behind letrozole (Femara), a breast cancer drug which was given to women as an aid to becoming pregnant, because it stimulates ovulation. It is also linked to miscarriage and birth defects [20], conditions which animals have proved entirely impractical to detect for, and are still used, despite superior non-animal methods being available.[21]

Some of these problems represent the impossibility of using animals to safety-test for humans. First, many results are impossible to detect – blurred vision, depression, compulsive gambling, and the effects which only show up after exposure over a few years – which is longer than the lifetime of lab animals, let alone test periods.

Next, there’s the false negatives. Animals falsely say there isn’t a risk when there is a risk. This happens for more than half of side effects which affect humans.[22]
Then there’s false positives. Animals indicate a risk, when there’s none – and 75% of ADRs which animals show are false.[23] Animal experimenters know this and know to ignore a lot of animals’ ADRs. The problem is, which ones should be ignored.

By contrast, there’s the technological, computer-based, clinical and common-sense ways of testing drugs. Cell culture tests alone have been found to be more accurate than animal tests, and they are just one method.[24]

In January 2006 Novartis were linked to a typical ADR scenario – treating a relatively minor condition and risking a life threatening one. Warnings were added to eczema cream Elidel after it was linked to cancer.[25]
Purdue Pharma has now had to withdraw its painkiller Palladone. The effect was typical of those undetectable by the tests on animals isolated in a laboratory: alcohol made it extremely dangerous. Alcohol had the effect of accelerating the release of the drug to fatal levels, a fact that was discovered by simple experiments like putting the pill in a glass of alcoholic drink.[26]

Danco Laboratories have had a boxed warning (the strongest possible) after its abortion pill Mifeprex (mifepristone) was linked with four cases of sceptic death. The bacteria has been identified, but too late for the four women who died and the others who may have been infected.[27]

Merck generated much of its income from Vioxx (painkiller) before it was found to be linked to an increased heart attack risk, and summer 2005 saw the first court trials find against the drug company. The first trial awarded a widow $253 million, and left others wondering whether it was tested at HLS animals by another of HLS’s customers.
Around the same time it emerged that animal data had indicated Vioxx protected the heart, and indicated it could be an effective heart drug, while human data suggested it was a heart risk.[28] Incredibly it seems the animal studies were given more credence than the clinical reports. As the trials progressed, an expert testified that a single dose could cause a potentially lethal heart attack.[29]

In November of 2005, the FDA added a warning to Merck’s Mevacor (lovastatin) Tablets[30], yet another ADR that was only discovered by unfortunate humans.
Another high-profile drug company in the headlines was Roche, who stopped recruiting for trials of cancer dug Avastin after deaths rose in the study group but not in the control group. Some of the deaths were suspiciously sudden.[31]

They also hit the headlines when ‘flu drug Tamiflu was linked to abnormal behaviour, hallucinations, and reports of two suicides – all among children. The European regulator requested a report on all psychiatric effects.[32] Although many of the events were in Japan, the American regulators also said they would “examine reports of up to 12 deaths and 75 cases of children who suffered health problems after using Tamiflu”.[33]

”Premature baby drug doubles risk” called the Daily Telegraph in January 2006, and again attention was turned to a HLS customer. Pacific Pharmaceuticals had released an antibiotic aiming to prevent premature birth. A study by experts and supported by baby health charity Tommy’s found it doubled the chance of a premature birth, causing an estimated 20 premature births every week.[34]

Astellas Pharma may not be a company instantly recognisable as a customer of HLS, but it was formed when Fujisawa Healthcare Inc. and Yamanouchi Pharmaceutical merged – two more recognisable names. Their Protopic, an eczema cream, was linked to cancer.[35]

Sanofi, another HLS customer, produced Ketek, an antibiotic. It has been linked with liver damage in patients and effects have included death and transplant. It was also linked to drug-induced hepatitis.[36] Sanofi-Aventis also produced DDAVP Injection (desmopressin acetate), which had a warning added by US regulators in November 2005.[37]
Previous to Vioxx, the big drug disaster was Baycol in the early 1990s. Manufacturer Bayer are still believed to be a HLS customer, and had warnings added to their drug Cipro in later 2005.[38] They were joined on the summary list of warnings that month by Abbott laboratories who had warnings added to Norvir (ritonavir capsules) Soft Gelatin & (ritonavir oral solution).[39]

That month Tracleer (bosentan) film-coated tablets also had an enforced warning after the discovery of previously unknown side effects. Manufacturer Actelion Pharmaceuticals is also a HLS customer.[40] Xyrem (sodium oxybate) Oral Solution also had ADRs discovered and a warning added at the same time, and the manufacturer is HLS customer UCB Pharma.[41]

Aranesp (darbepoetin alfa) for Injection (manufactured by Amgen) and Effexor XR (venlafaxine hydrochloride) Extended-Release Capsules (Wyeth-Ayerst Laboratories) were also the subject of warnings, and made by HLS customers.[42]

The FDA summary list for the month also included NovoSeven Coagulation Factor VIIa (Recombinant) (Novo Nordisk), Ortho Evra (norelgestromin /ethinyl estradiol transdermal system) (Ortho McNeil Pharmaceuticals) and Tarceva (erlotinib) Tablets (OSI Pharmaceuticals/ Genentech).[43] As these were all HLS customers, it seems that in one month’s warnings, many of the drugs involved were potentially ‘safety-tested’ by HLS.

In February 2006 a report into Adderall a drug made by HLS customer Shire Pharmaceuticals, linked 24 deaths to this drug for Attention Defecit Disorder, and experts urged monitoring of the effect of the drug on the heart.[44] If HLS did test the drug for Shire, could there have been problems with the animals tests? Considering differences in blood pressure, the blood circulation system, diet, lifespan, stress levels, and almost all lab animals walking on four legs not two (which alters blood supply and the work the heart does radically) means there is no animal model of any value for the heart.

Another ADHD drug, Ritalin was referred to in a report by the US regulators early in 2006 which said there were concerns over the heart risks of the drug.[45] Manufacturer Ciba-Geigy Corporation is a division of Novartis, a long-term, high profile HLS customer. The problem also applies to Concerta[46], made by Janssen-Cilag, part of Johnson & Johnson – a customer of HLS.

Johnson & Johnson have also been implicated in their own right. An analysis of the data available on their heart failure drug Natrecor (nesiritide) showed the likelihood that it caused a higher risk of death or renal damage.[47] A whistleblower from the FDA, David Graham, stated that this drug could possibly be as dangerous as Vioxx.[48]

Animal tests are not capable of predicting the side effects of a drug. Previously, the Scientific Executive of HLS admitted that they were able to predict with an accuracy of about 5%-25%.[49] When animals do show side effects when they’re given a drug, research has shown that most of the time, they’re showing something that will not happen in humans. Studies have shown that 75% of these unwanted affects never result in humans. [50]

Conversely side effects happen in humans that are not predicted by animal experiments. The terrible effects suffered just by the patients affected the drugs mentioned above are examples of what can happen if you take a drug which has successfully passed animal tests. Unfortunately, these events are just part of a massive problem, and the human casualties of vivisection are numbered in their hundreds of thousands every year.[51]

1 http://www.reuters.co.uk/newsArticle.
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2 http://www.philly.com/mld/inquirer
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8 Oklahoma News Channel 8, 16 November 02
9 Painkiller 'may double risk of heart attacks'
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10 http://edition.cnn.com/2006/HEALTH/03/17/
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11 http://www.timesonline.co.uk/newspaper/
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12 http://news.independent.co.uk/uk/health_
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13 http://www.fda.gov/medwatch/safety/2005/
safety05.htm#Strattera
14 D. Mail 2.9.05 "HAPPY PILLS
COULD CAUSE BIRTH DEFECTS"
15 http://www.msnbc.msn.com/id/8543848/
Popular Parkinson's drug linked to gambling. July 11, 2005
16 http://www.thisismoney.co.uk/news/article.
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18 MedWatch - The FDA Safety Information
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21 Biogenic Amines (Vol. 19, No. 2, pp. 97–145 (2005))
22 Clin Pharmacol Ther 1962; pp665-672
23 AP Fletcher in Proc R Soc med, 1978;71, 693-8
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26 http://www.latimes.com/news/printedition/asection
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27 http://www.fda.gov/medwatch/safety/2005/safety05.
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28 http://www.timesonline.co.uk/newspaper/0,,2762-
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30 http://www.fda.gov/medwatch/SAFETY/2005/nov05.htm
31 http://www.dailynews.com/business/ci_
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32 http://www.marketwatch.com/news/story.asp?siteid=
mktw&dist=moreover&guid={499A769D-F9DD-4E17-
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33 http://www.msnbc.msn.com/id/10089186/
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34 Daily Telegraph. 13 January 2006.
35 Daily Record. 20 January 2006. Novartis drug gets 'black box' warning
36 http://framehosting.dowjonesnews.
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37 http://www.fda.gov/medwatch/SAFETY/2005/nov05.htm
38 http://www.fda.gov/medwatch/SAFETY/2005/nov05.htm
39 http://www.fda.gov/medwatch/SAFETY/2005/nov05.htm
40 http://www.fda.gov/medwatch/SAFETY/2005/nov05.htm
41 http://www.fda.gov/medwatch/SAFETY/2005/nov05.htm
42 http://www.fda.gov/medwatch/SAFETY/2005/nov05.htm
43 http://www.fda.gov/medwatch/SAFETY/2005/nov05.htm
44 http://go.reuters.com/news
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45 http://www.news-medical.net/?id=15843
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46 http://www.news-medical.net/?id=15843
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47 Sackner–Bernstein, J. et al. JAMA 293, 1900–1905; 2005
48 Friday 27 January 2006 Pharma's year of trouble
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49 'Animal Toxicity Studies:Their relevance to
man Lumley & Walker (ed) pp57-67, Quay, 1989
50 AP Fletcher in Proc R Soc med, 1978;71, 693-8
51 Journal of the American Medical Association. 14/4/98