Tagged: Malaria

Is Tafenoquine Another Drug Disaster In The Making? ..


When he was interviewed by Evan Davis (of the BBC see here)-  GSK’s (former CEO) Andrew Witty said: ‘On the one hand we have wonder drugs and on the other danger drugs”. What he meant was- the pharmaceutical industry has a bad reputation because some of their drugs released on the market can cause immeasurable harm to unsuspecting patients, while others can no doubt help patients. There are the GSK danger drugs- like Seroxat/Paxil and Avandia, and many more from other pharmaceutical companies- Vioxx being one of the most well known examples..

Will GSK’s Tafenoquine will turn out to be a danger drug or a wonder drug? This remains to be seen.

However, according to Dr Remington Nevin (check him here), GSK’s Tafenoquine is already turning out to be quite the danger drug…

How many people will get neuro-toxic side effects from Tafenoquine when it hits the US market? It looks like we’re just about to find out…

http://www.pharmatimes.com/news/gsk,_mmv_submit_malaria_drug_in_the_us_1212942

 

GSK, MMV submit malaria drug in the US

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GlaxoSmithKline and the Medicines for Malaria Venture are seeking permission to market single-dose tafenoquine in the US to prevent relapse of Plasmodium vivax malaria.

The application, which relates to patients 16 years of age and older, is based on data from the GATHER and DETECTIVE trials.

The Phase III DETECTIVE trial showed that a statistically significant greater proportion of patients treated with single-dose tafenoquine (60 percent) remained relapse-free over the six-month follow-up period than patients on placebo (26 percent).

The GATHER trial investigated a single-dose of 300mg tafenoquine on levels of haemoglobin when compared to a 14-day course of 15mg primaquine, and showed that the incidence of decline “was very low and similar between the two treatment groups”, at 2.4 percent versus 1.2 percent, respectively.

GSK and MMV note that, if approved, tafenoquine would be the first new medicine for the prevention of relapse of P vivax malaria in more than 60 years, “potentially addressing the need for a single-dose and effective medicine for this debilitating disease”.

“One of the greatest challenges for patients with P. vivax malaria is preventing relapses,” said Patrick Vallance, president of R&D at GSK.

“Being able to treat patients with a single dose of medicine would be an important step forward in ensuring efficacious treatment, thereby reducing the risk of relapse, particularly in areas with very limited healthcare infrastructure.”

 

 

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GSK’s Tafenoquine Scandal Hitting The Mainstream….



Thanks Stewart..

 


http://www.9news.com.au/national/2017/08/30/11/23/australian-veterans-say-they-suffer-toxic-effects-of-anti-malaria-drug

Australian veterans fighting toxic side effects of anti-malaria drugs

12:26pm Aug 30, 2017

Play Video
9RAW: Anti-malaria drugs linked to Australian veterans’ chronic brain injuries

Schizophrenia, hallucinations, seizures and self harm are among the disorders allegedly affecting Australian service men and women who trialled controversial anti-malaria drugs.

The drugs were given to the military personnel from 1999 to 2002 while deployed to East Timor and Bougainville as part of international peacekeeping missions.

The precise numbers who received them is uncertain, but campaigners say one drug, mefloquine – also known as lariam – was given to about 1300 servicemen and servicewomen.

They believe another experimental pharmaceutical tafenoquine was issued to 1500 members of the ADF.

Some veterans insist they were compelled to take the drugs.

While the Defence Department says only a small number of veterans have suffered adverse serious effects, there is speculation that hundreds of Australian military personnel may have been diagnosed with chronic brain injuries and psychiatric conditions.

These effects can often be mistaken for post-traumatic stress disorder.

Some veterans who took the drugs have reported suffering bipolar disorder, schizophrenia, major depression and anxiety, seizures, hallucinations and psychosis, suicide attempts and suicide.

Major Stuart McCarthy, right, is being treated for an acquired brain injury after being exposed to mefloquine, developed by US army doctors during the Vietnam War, left. (Main photo: AP). Major Stuart McCarthy, right, is being treated for an acquired brain injury after being exposed to mefloquine, developed by US army doctors during the Vietnam War, left. (Main photo: AP).

Melbourne-based veteran Mick Kruizinga was given tafenoquine after contracting malaria before being given mefloquine on a second tour of East Timor. The 41-year-old former infantry man has since experienced severe health problems.

“The last eight years he has had major problems and he is getting worse,” his wife Naomi Kruizinga told nine.com.au.

She said his health problems include lesions on his brain as well as high toxicity in his blood system.

But the Kruizingas have received little from the Australian Government, with Mick being refused a Gold Card – which entitles holders to health care treatment funded by the Department of Veteran Affairs.

Instead, the family have paid for Mick Kruizinga’s costly and lengthy medical treatment themselves.

Australian soldiers serving in East Timor during 2000 to 2002 were given the anti-malaria drug mefloquine. (Photo: AAP).Australian soldiers serving in East Timor during 2000 to 2002 were given the anti-malaria drug mefloquine. (Photo: AAP).

Campaigner Major Stuart McCarthy, who is undergoing treatment for an acquired brain injury after being exposed to mefloquine and tafenoquine, claims the ADF trialled the drugs on a “captive audience” of volunteers.

McCarthy whose overseas service included the Middle East, Africa and the Asia Pacific, told nine.com.au he volunteered to take the drug while deployed in Bougainville after a “sales pitch” by a high-ranking army doctor.

“We were a captive audience … we believed we could trust him with our health.”

Last week, the Repatriation Medical Authority – the government body that determines Statements of Principles for any disease, injury or death that could be linked to military service – dismissed any relation between brain injury and antimalarial drugs after a government investigation.

The authority ruled there is insufficient evidence that exposure to the antimalarial drugs mefloquine, tafenoquine or primaquine causes chronic brain injury.

Retired Colonel Ray Martin said the decision was disappointing.

He told the Townsville Bulletin: “Sadly it often takes decades for the devastating effects of toxic substances to be fully recognised”.

A file photo showing survivors of a shooting rampage by US soldier Robert Bales in 2012. This month he asked a military court for a special hearing to explore evidence his actions were linked to taking mefloquine. (Photos: AP).A file photo showing survivors of a shooting rampage by US soldier Robert Bales in 2012. This month he asked a military court for a special hearing to explore evidence his actions were linked to taking mefloquine. (Photos: AP).

“The concern today is that hundreds of servicemen and women who have been badly affected by mefloquine are still being misdiagnosed and mistreated, almost two decades on after being used as experimental guinea pigs.”

Mefloquine and tafenoquine were developed by the US military’s anti-malarial drug program at the start of the Vietnam War in the 1960s.

By the late 1990s mefloquine was known for serious side effects and ceased to be produced in many countries. It has been linked to many murders, suicides and war crimes over the past two decades and is now used as a drug of last resort by the ADF.

Earlier this month, US Army Staff Sergeant Robert Bales who was convicted of killing 16 Afghan civilians during a shooting rampage in 2012, asked a military court in Virginia for a special hearing to explore evidence that his actions may have been linked to mefloquine, reported the New Observer.

Last year an inquiry by the ADF’s Inspector General reported the “drug trials were conducted ethically and lawfully”, that soldiers volunteered to participate, and that anyone who was sick could be treated for free.

But today the effects of the anti-malarial drugs on service men and service women from a range of countries is under renewed scrutiny.

Concerns have sparked a number of high-level inquiries being held in the US, Canada, Germany and Britain. Germany has gone as far as banning the use of mefloquine.

Dr Jane Quinn, a neuroscientist and neurotoxicologist at Charles Sturt University in Bathurst NSW, who moved to Australia from Britain, has expert knowledge and a tragic personal link to the issue.

Her late husband Major Cameron Quinn, a British Army officer, was given mefloquine during a training exercise in Kenya in 2001.

She told nine.com.au he suffered depression, nightmares and long-term personality change for years before taking his own life in 2006.

Dr Quinn subsequently campaigned for mefloquine to be axed by the British armed forces. Since moving to Australia, she works as a senior lecturer and helps veterans and their families confront the debilitating effects of the drug.

After taking Lariam my husband was a changed man forever. He went from someone who had never had any mental health problems to a man who started to suffer bouts of suicidal thoughts, depression, anxiety and volatile behaviour,” she said.

Dr Quinn is certain the controversial drug was behind his death.

“I am convinced that the side-effects of Lariam killed my husband. Since his death I have become aware of many other soldiers who have suffered dreadful psychological problems after taking this drug.

“I find it hard to understand why a drug known to cause permanent brain damage and serious psychological problems is still being given to soldiers, or anyone.”

A spokesperson for the Department of Defence told nine.com.au: “Defence has published a significant amount of information on this matter as part of ongoing efforts to assist those with concerns regarding the use of mefloquine in the ADF.”

“That information includes details on the deadly impact of malaria, anti-malarial medications, research publications, an IGADF (Inspector General of the ADF) inquiry report, and the support services that are available, and can be found at www.defence.gov.au/Health/HealthPortal/Malaria/default.asp.”

An Emerging GSK Scandal -(Tafenoquine) : Psychosis, Bipolar and Chronic Depression: Personal Account of an Australian Tafenoquine Veteran


Posted on June 27, 2016 by International Mefloquine Veterans’ Alliance
This is the personal account of an Australian soldier who deployed to Timor Leste with the 1st Battalion, Royal Australian Regiment (1 RAR) in 2000-2001. During this tour 1 RAR soldiers were used to trial the experimental quinoline anti-malarial drug tafenoquine, manufactured by GlaxoSmithKline, in one of a series of tafenoquine studies undertaken by the Army Malaria Institute. The Department of Defence claims that “there is no evidence that tafenoquine causes serious neuropsychiatric effects, either acute or chronic”, only by ignoring the fully documented medical histories of this veteran and many others like him.
Among the 492 tafenoquine trial subjects, not one single severe neuropsychiatric adverse event was attributed to their use of this drug in the published trial report. Yet there are scores who were subsequently diagnosed with serious, chronic psychiatric disorders including depression, anxiety, PTSD, bipolar and other personality disorders. Many were medically discharged from the Army and remain chronically ill, while the Department of Defence refuses to accept any responsibility or to undertake follow-up studies.
This account is typical among the survivors of the trial.
“I was put in the locked psychiatric ward at Townsville under close surveillance and remember being isolated with some other very mentally sick people. What I went through there in hospital can’t really be explained to someone who hasn’t crossed the line to insanity.” 

I was 19 years old when I was deployed on Operation Tanager to East Timor. To be a soldier was all I ever wanted to be and I joined  because I wanted to make a difference and help people. I was a soldier of 2 platoon Alpha Company 1 RAR, and I was prescribed Tafenoquine as part of the anti malaria drug trial in 2000.

A lot of things happened over there on tour that had a great impact on my life. It’s been 15 years since I returned home from that deployment and the following is a summary of what has happened after my battalion returned from war-like service on Anzac Day 2001.

Like most of us, I had some trouble adjusting to society when we came back to Australia. The first thing out of the ordinary for me was that I just felt like being alone. That wasn’t normal behavior for me and I turned down invitations from friends to just stay inside on my own for days. I felt a bit shut off and I became more withdrawn and in particular from strangers and civilians. I found when my mind was occupied with work though, I seemed to be doing alright and I didn’t really think it was a problem at the time.
Later that year in 2001 was where things started to go very wrong for me. My mind started to deteriorate over a period of 2 months which lead me for the first time down the path of mania. Initially I was in good health and felt great. I had a happy and positive outlook and a huge thirst for life. I felt really strong, confident, and powerful. I started noticing I seemed to have a lot more energy than ever before, and my thoughts began to slowly race.
Things that seemed difficult before were now quite simple to me. My mind was very sharp and fast and was getting faster each day. So much so that it began working overtime. In a space of 2 weeks I rarely slept, I remember walking the line between dreaming and being awake and thinking that I was fine, when in reality I had lost 20kg from over-exercising, looked exhausted and was talking so fast and rapidly shifting from one subject to the next that no one could understand me. I was becoming irritable, quick to anger and quicker to another emotion in an instant. Any fear or inhibitions holding me back were gone, and I would wake to a new day excited like it was an epic adventure. I started to believe I had a heightened sense of state as ordinary things or circumstances started to communicate with me on a second level to what I would normally understand. I found intricate meaning in anything that I was immersed in which would be entirely delusional to anyone but myself. I was completely irrational and psychotic, and it wasn’t until I didn’t show up for parade one morning that I completely lost it. I have trouble remembering, but I’m told that I was found in my room which was in a state of chaos, and I remember my boss bringing me some food and taking me to hospital.
I was put in the locked psychiatric ward at Townsville under close surveillance and remember being isolated with some other very mentally sick people. What I went through there in hospital can’t really be explained to someone who hasn’t crossed the line to insanity. To give you an indication of my thought process though, I believed I was at the centre of some extraordinary story where I’d been taken to a facility not of this Earth, and that the people I met were reincarnated versions of others I once knew.
To say the least, for me to come back to reality was a long, slow and difficult process. I had no idea what was happening to me, and was under very heavy drug sedation. I eventually came to grips with the fact that I was told I had a major psychotic episode and needed time in hospital to recover which played out to three months.
I was put on leave and sent home to be treated as my family tried to piece together what was happening. My memory of this time is hazy as I was heavily sedated and physically unable to get out of bed at times from the medication. After 4 or 5 visits to a Psychiatrist I was diagnosed with Bipolar Disorder. I didn’t know what that was and to this day I think doctors have a hard time understanding it themselves but the diagnosis lead me to understand that my future in the services was over. I lived and breathed the Army so this was very hard to take. The day I was told that I would be medically discharged was probably the most I’ve ever felt ashamed and lost.
A couple of amazing Vietnam Vets tried to help me when I was first discharged. I was still in a daze from the medication the doctors were trying to treat me with and frankly in a bit of shock from what I had been through. An advocate put together a case for me on my behalf. I kept quite a comprehensive written journal of my accounts in Timor but any evidence I had was not enough to support my claim for Bipolar Disorder.Timor was new and I needed to show evidence that I had been through a  stressor significant enough with the diagnosis of Bipolar Disorder being within 6 months of that stressor to warrant a claim.

When presenting my case coincidentally on Remembrance Day the Vets on the board asked whether I had been in any contacts or fired my weapon throughout the tour. When I answered no, I knew my claim would be denied and it was.
Since my discharge I’ve tried to live my life as best as I could, but I soon discovered new problems. I had my first taste of major anxiety and depression in early 2004. I slowly started withdrawing into myself and lost more and more of my personality over a few weeks to a point where my mind felt numb, and everything I did seemed like I was just going through the motions of basic communication. I felt on edge and my cognitive skills were almost freezing up as I couldn’t function or make a decision. This was new and I tried to escape from it by drinking heavily one night. I remember waking up the next morning frozen with what I now know is anxiety. I knew I needed to call for help but couldn’t work out what to say or how to do it and felt just about paralyzed in my mind. I had to once again recover and quit my job and move home for my family to take care of me.
What followed was a long drawn out depression. It would hold on to me and little I can do to this day can help it. When depression comes it comes, and I just have to hope for the best, but when it does come, suicidal thoughts come with it leading to suicidal ideation. In the trough of depression it’s close to the only thought that you have. You’re mind convinces you it’s the only choice that’s left to solve what’s happening. For me, it’s not a feeling of sadness, it’s a feeling of nothing at all. It’s just about the opposite of mania, you’re mind runs slowly, and simple tasks seem overwhelming. You just want to be alone, you don’t want to do anything, and you just want to die. I’ve had more depressive episodes than I can say, and have been close to being hospitalised for it on a number of occasions. They can last for months on end and the anti-depressant medication treatment I’ve had for it doesn’t seem to have any effect.
I was 23 by this stage after going through these two major episodes and started to have little hope for my future. I took a very basic job at a factory where I worked along side older people that had trouble mentally but were able to put in a days manual labour. It was hard for me because despite my psychological problems I was reasonably bright and young.
I had a lot of nightmares, and continue to have one vivid reoccurring one where I’m in a contact scenario back in Timor with my section. Each dream is in a new location but it’s always the same, I can’t seem to find my weapon while my mates and I comes under fire. I wake up in terror and a cold sweat. I find occasionally in social situations I get a similar cold sweat and I panic. I avoid anything army, in particular Anzac Day or anything that reminds me about my service which I find hard as some of my closest friends still serve and I have a respect for it. I’ve found in the past when I bring things up, or relive what I went through on deployment it often leads to me becoming unwell. 

The fear of that first psychotic episode is what keeps me in check. I’ve had several further manic episodes and they seem to come when I’m under stress. The most recent one I had was quite severe and I was starting to lose my grip on reality again with delusions and seeing signs in ordinary things. I’d take wild risks in decisions and not consider the consequences. Some of the thoughts I’ve had in these times I won’t mention but could have lead to some dangerous scenarios. I would show signs of violence, bursts of anger, just breaking down emotionally, and generally not be in control of myself. You try to use your brain to figure out how to solve the situation, but the problem is your brain is the part that’s broken. Each time I have an episode, my mind seems to be in a worse state than before. I get headaches, my short term memory deteriorates, and my focus or concentration to stay on a simple task at times seems more confused. People will talk to me and quite often I’m far away. Im still a bit unsure of the cause of what has happened to me. All I know is this – I went to Timor fit and healthy, and didn’t return that way and have never been the same since.

Despite what has happened to me, somewhere deep down is that 19 year old soldier that doesn’t give in. I fight to hold on to who I am, and not let things get to me. Some days I lose though, weather the storm and lock myself away from the world for a day or two, but I carry on.
I’ve managed to persevere and live a pretty good life of sorts really. There were long periods where I was healthy and it was here I managed to do really well. With the money I made in Timor, and from the factory I had a deposit to buy a house. I left the factory, studied, travelled, opened a business, got married and started a family. Throughout all this I’ve cycled through mental health problems and states of mania, depression and anxiety. Sometimes I have outbursts of these problems where they’re short lived or blend together.
In 2009 my girlfriend who is now my wife experienced what happens to me when I have a major depressive episode. She didn’t know what to do at first as I became more distant and withdrawn and slowly couldn’t communicate what was happening to me. It got pretty severe quite quickly and I ended up at hospital once again. This time I managed to get some help. I met with some new doctors who were a bit more in touch with young veterans. Since then I’ve been treated by a psychiatrist for Bipolar Disorder. After all this time with him I’ve rarely spoken about my deployment but talking with him has helped me stay on track with my condition. For a long time I was taking Epilem to control my moods, and sleeping medication when necessary to reduce the risk when I go high in mania but I’ve been drug free now for over 18 months and reasonably healthy. I know what the future holds for me though, and what has happened to me is permanent. I think what hurts me the most is putting my family through the process.
I owe my life to my family and friends. Without them or an understanding support network, I wouldn’t be here. Strangely, I’ve also found having looked after a dog has helped. It gets me out of the house and my dog’s outlook on life is pretty inspiring. Physical fitness or activities have also really helped when I’ve been depressed. Forcing myself to go out and be with friends. A job that keeps my mind occupied and gives me a purpose. The belief that no matter how deep or dark a depression is, that it will one day eventually pass. A good night sleep and not too much stress to set things off. I’ve found that having a sense of humor has helped me through the years. A Vietnam Vet once said to me that when you’re a digger, if you’re platoon went through a bad situation you would have a laugh along the way, and that’s how you get over things, deal and survive. I think also that none of us fought in Timor on our own.
Going on tour to help the East Timorese was one of the defining moments of my life. I haven’t been in contact with anyone I served with for nearly 15 years now and being isolated hasn’t really helped me. For a long time I literally thought I was a minority, mentally weak and just unfortunate for what happened to me. A friend recently sent me a link to the online group for us Timor vets and it’s answered a lot of questions. I hope to answer more and personally with what I went through hope to find peace in knowing that I wasn’t at fault for what I’ve suffered. I also hope to live the rest of my life as mentally healthy as I can, and that one day I can pay back my friends, family and the great people who have helped me.

Is There Something Dodgy Going On With GSK’s Tafenoquine?


Tafenoquine is an experimental anti-malaria drug manufactured by GSK. It seems it might be just as dodgy as Roche’s Lariam (see here). Personally, after experiencing the horrors of Seroxat, I wouldn’t ingest any GSK product, and why would I?

Seroxat was horrific.

A great website worth checking out in relation to these drugs is

internationalmefloquineveteransalliance.org

And check out the post below for more on GSK’s Tafenoquine-


https://internationalmefloquineveteransalliance.org/2016/05/21/scientific-misconduct-in-the-australian-army-malaria-institutes-clinical-trials-of-tafenoquine-part-1/

Scientific Misconduct in the Australian Army Malaria Institute’s Clinical Trials of Tafenoquine – Part 1

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The New Mefloquine?

Mefloquine is now well known to be neurotoxic, one of several synthetic quinolines able to cause acute psychotic reactions and/or a chronic central nervous system (CNS) toxicity syndrome in a significant proportion of people given these drugs for malaria prophylaxis. The licencing of mefloquine by national drug regulators in the late 1980s and early 1990s occurred in the absence of phase III clinical safety and tolerability trials among normal study populations of healthy civilian volunteers. Instead the approvals relied on studies among vulnerable subjects including prisoners, military personnel and people in developing countries. The result of this regulatory failure is described by Dr Ashley Croft:

“Effectively, all users of Lariam, from the point of licensing onwards, have been involved in a natural experiment to determine the true safety margin, at current dosages, of [this] poorly understood antimalaria drug. Consumers have been unwitting recruits to this longitudinal study, rather than informed partners.”

Much of the recent media coverage of mefloquine’s adverse health effects has focused on the efforts of military veterans, including drug trial subjects, in seeking appropriate recognition and medical care from their national governments. Prominent among these are Australian veterans who participated in clinical trials conducted by the Australian Army Malaria Institute (AMI) in Timor Leste from 2000 to 2002. With doxycycline malaria prophylaxis having been pioneered by AMI in the 1980s in response to resistance in other drug classes, mefloquine has never been the first line anti-malarial in the Australian Defence Force (ADF) and was prohibited from being used by aircrew and other specialist personnel due to its neuropsychiatric side effects. This has led us to question why the drug was “trialled” for use in the ADF long after it had been registered, with its neuropsychiatric side effect profile so evident in the civilian market and previously published military drug trials. What has become apparent is that ADF personnel given mefloquine during these trials were simply “collateral damage” in an effort to support the development of another synthetic quinoline anti-malarial drug – tafenoquine.

The story of tafenoquine’s development and introduction to date is alarmingly similar to the story of mefloquine – marred by regulatory shortcuts, cosy relationships between military officials and the pharmaceutical industry, breaches of ethical standards, scientific fraud and medical negligence. This is the first in a series of posts that aims to document this misconduct by ADF officials involved in the AMI’s clinical trials of tafenoquine. In this post we will provide background on tafenoquine and an overview of the trials, then in subsequent posts we will describe the conduct of each trial and the emerging evidence of misconduct.

Tafenoquine

Tafenoquine is an 8-aminoquinoline drug manufactured by GlaxoSmithKline (GSK) that is being investigated for prophylaxis and treatment of malaria. Like mefloquine, tafenoquine is a synthetic quinoline that was first developed by the U.S. Walter Reed Army Institute for Research (WRAIR) as part of an enormous anti-malarial drug discovery program that commenced during the Vietnam war. Two of the drugs developed earlier in this program were mefloquine (Lariam™) and halofantrine (Halfan™).

The first investigation of tafenoquine in this program was in the treatment of relapsing vivax malaria, as a more effective alternative to primaquine. Later it was seen as a useful preventative against multi-drug resistant falciparum malaria. A series of pre-clinical studies were undertaken from the late 1980s to the late 1990s, with clinical studies commencing in the late 1990s using “volunteers” in the U.S., Thailand, GabonKenya and Ghana. Researchers who were instrumental in these studies and later moved to Australia include former AMI Director Karl Rieckmann, the current AMI Head of Drug Evaluation Michael Edstein, and the current AMI Director Dennis Shanks. Further studies were conducted with Australian military personnel in the 1999-2001 clinical trials that are the subject of this post, while Rieckmann was the Director of AMI.

Despite these AMI trials having found tafenoquine to be safe and effective, the drug’s clinical development did not substantially progress towards registration for almost decade. Eventually, in 2008 the manufacturer GlaxoSmithKline (GSK) entered an agreement with Medicines for Malaria Venture (MMV) to develop tafenoquine as a radical cure for vivax malaria. Five years later the U.S. Food and Dug Administration (FDA) granted “breakthrough therapy” designation for tafenoquine, and several months later GSK and MMV announced the commencement of Phase III clinical trials. The FDA states that Breakthrough Therapy designation “is intended to expedite the development and review of drugs for serious or life-threatening conditions”, and “conveys all of the fast track program features, more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and eligibility for rolling review and priority review.”

Another parallel with the mefloquine story is that there has been a reluctance to undertake laboratory studies of tafenoquine’s potential neurotoxicity prior to registration. Like another 8-aminoquinoline primaquine, tafenoquine is able to cause haemolytic anemia in individuals with G6PD deficiency, and many of the clinical studies have carefully assessed this toxic property. However the 8-aminoquinoline class includes several other drugs that are also known to be neurotoxic, including pamaquine and plasmocid, based on extensive histopathological testing conducted as long ago as the 1940s. A leading expert in quinoline toxicity wrote in 2013:

“While tafenoquine has been eagerly anticipated for its utility against vivax malaria and potentially against leishmaniasis, the recent granting by the U.S. FDA of Breakthrough Therapy status, in the absence of any published neurohistopathological testing, risks recreating the sense of urgency that contributed to the approval of mefloquine in the absence of appropriate CNS safety data.”

Yet In 2009, long after the AMI tafenoquine trials in Bougainville and Timor Leste, a study comparing in vitro toxicity levels between various anti-malarial drugs co-authored by WRAIR scientists found that tafenoquine is “more neurotoxic than mefloquine.” More recent laboratory studies have also raised doubts about the efficacy of tafenoquine, finding that the CYP2D6 enzyme is involved in metabolising the drug in several ways that affect the drug’s toxicity as well as its effectiveness as an anti-malarial. CYP2D6 levels are highly variable from person to person, which may also answer why the drug’s neurotoxic effects vary from person to person.

Emerging Evidence of Misconduct

Evidence of the misconduct documented in this series is drawn from a variety of sources, many of which are now publicly available. These include published trial reports, related journal articles, minutes of Australian Defence Human Research Ethics Committee (ADHREC) meetings, a review of ADHREC annual reports that matches approved trial protocols to published reports, media reports, and other documents from Defence, GlaxoSmithKline and the Australian Therapeutic Goods Administration (TGA). Additionally, hundreds of the trial subjects have recently formed an Australian Mefloquine and Tafenoquine Veterans group to share and publicise their personal accounts.

Several years after the AMI’s tafenoquine and mefloquine clinical trials in Timor Leste, hundreds of the ADF subjects initiated legal action against Defence, reporting that they were not adequately informed of side effects and complaining of symptoms such as depression, paranoia, and suicide ideation. When this story was first reported in the media in 2004, ADF Surgeon General Tony Austin initially claimed that the number of personnel involved in these trials was in the “dozens rather than hundreds”, however Chief of Army Peter Leahy admitted several days later that the actual number of trial subjects in Timor Leste was 1,351. The legal action was discontinued after the Australian government introduced legislation that would have required them to forfeit veterans entitlements in the event their claim succeeded. The majority of these veterans continue to experience chronic neuropsychiatric disorders including depression, anxiety, misdiagnosed PTSD, personality disorders and conversion disorders. Many of them were discharged from the ADF on medical grounds, now suffering debilitating side effects of anti-psychotic drugs prescribed off-label, and there have been a number of suicides.

The published study findings and other official ADF reports of these trials universally portray tafenoquine as a “safe” and “well tolerated” anti-malarial drug. As public scrutiny has intensified in recent months, senior Defence officials have insisted that serious neuropsychiatric side effects from tafenoquine are rare. However the disturbing truth is that the incidence of acute psychotic reactions and chronic neuropsychiatric illness attributable to the use of tafenoquine in these trials almost certainly meets the MedDRA definition of “common” (1-10%) or “very common” (>10%). There can be little doubt that the published findings of these trials constitute comprehensive scientific fraud, achieved in a number of ways that will be more fully documented in subsequent posts, including:

  • Providing false and/or misleading information to the trial subjects.
  • Coercing subjects into participating in the trials.
  • Relying on the prevailing stigma of mental health problems to minimise subject reporting of neuropsychiatric adverse effects.
  • Recording serious adverse events as “withdrawals” to avoid attributing them to the trial drug in the published study report.
  • Misattributing adverse events to extraneous causes.
  • Failing to include follow up medical examinations in trial protocols, to avoid recording chronic adverse effects attributable to the drug.
  • Failing to publish reports for several of the ADHREC-approved trial protocols, most likely to conceal unfavourable findings.
  • Failing to note known limitations in malaria reporting systems in the published study reports, resulting in over-estimations of tafenoquine’s anti-malarial efficacy.

Ethical Standards

The relevant ethical standards for the conduct of these clinical trials are laid down in the TGA’s Note for Guidance on Good Clinical Practice, which is mandated by the National Health and Medical Research Council Act. This standard describes “members of the armed forces” as vulnerable subjects “whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.” Relevant provisions in these standards include:

  • “Foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society.”
  • “The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.”
  • “During and following a subject’s participation in a trial, the investigator/institution should ensure that adequate medical care is provided to a subject for any adverse events, including those related to the trial.”
  • In obtaining the informed consent of trial subjects, the institution should adhere to “the ethical principles that have their origin in the Declaration of Helsinki.”

Chronology of the Tafenoquine Trials

The tafenoquine trials on ADF personnel are summarised in a 2011 PhD thesis by Dr Peter Nasveld and included:

Part 2

Part 2 of this series will examine the emerging evidence of misconduct in the c. 2001-2002 clinical trial of tafenoquine in the treatment of recurrent vivax malaria. Subsequent posts will address the larger prophylaxis trials. These will be updated as additional evidence becomes public.

References

P. E. Nasveld, Tafenoquine in the prophylaxis and treatment of malaria in Australian Defence Force personnel, PhD thesis, James Cook University, 2011.

P. E. Nasveld, M. D. Edstein, M. Reid et al., Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects, Antimicrobial Agents and Chemotherapy, vol. 54, no. 2, pp. 792–798, 2010.

S. Kitchener, P. Nasveld and M. Edstein, Tafenoquine for the treatment of recurrent Plasmodium vivax malaria, American Journal of Tropical Medicine & Hygiene, vol. 76, no. 3, pp. 494-6, 2007.

P. Nasveld, S. Kitchener, M. Edstein and K. Rieckmann, Comparison of tafenpquine (WR238605) and primaquine in the post-exposure (terminal) prophylaxis of vivax malaria in Australian Defence Force personnel, Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 96, no. 6, pp. 683-684, 2002.

Therapeutic Goods Administration, Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95), Department of Health and Ageing, Canberra, Australia, 2000.

Are GSK’s Experimental Malaria Drug Tafenoquine And Roche’s Mefloquine (Lariam) Neurotoxic?


TAFENO

“…British soldiers are being given a controversial malaria drug that carries a higher risk of depression, anxiety and psychosis compared to its alternatives, an inquiry heard yesterday.

Dr Frances Nichol, of drugs manufacturer Roche, admitted to the Defence Select Committee that the drug Lariam, used by the military, had worse side effects than other common anti-malarials.

She warned that the drug should not be prescribed to soldiers with pre-existing conditions. But another Roche spokesman admitted there was a ‘risk’ that military personnel might not disclose previous mental health problems to officers for fear of damaging their careers…”

Daily Mail 2015

Roche’s anti-Malaria drug Mefloquine (which goes under the trade name Lariam) is a Malaria drug which has been dogged by controversy for at least a decade now. Roche were sued in Ireland recently because of the neuro-toxic effects of Lariam (there was an out of court settlement).

“….http://www.irishtimes.com/news/ireland/irish-news/action-over-alleged-effects-of-anti-malarial-lariam-settled-1.2390535

In proceedings initiated in 1999, Mr Bryce sued Roche Products (Ireland) Ltd; a medical doctor and Executive Medical Care Ltd, trading as Grafton Street Medical Centre, for damages for allegedly failing to warn him of all of the side-effects of the drug.

Mr Bryce claimed his delay in prosecuting his action was allegedly due to poor health since having taken the drug.

Mr Bryce had claimed he took Lariam prior to his honeymoon in Kenya in 1996.

He claimed he suffered panic attacks and dizziness and his health had deteriorated after returning from his honeymoon….”

The neuro-toxic effects of Roche’s Lariam have been well documented now, however GSK are developing their own anti-Malaria drug (which has yet to be fully licensed) called Tafenoquine.

Tafenoquine is in the same class of drug compounds as Mefloquine and there has been speculation that Tafenoquine could be even more neuro-toxic than Mefloquine (Lariam).

RNEVEN

Dr Remington Nevin has been studying the neuro-toxicity of these drugs and there seems to be a lot of concerns raised about GSK’s Tafenoquine…

After the devastation caused by GSK products such as Myodil, Avandia, Seroxat and Pandemrix  I think the public have a right to be concerned when GSK claims to have made a breakthrough drug don’t you?…

Seroxat (Paxil) was marketed as a breakthrough wonder drug for the treatment of depression and anxiety in the late 90’s but it wasn’t long after that people began to realize that Seroxat was closer to a killer drug than a wonder drug…

I will be keeping my eye on  GSK’s Tafenoquine…

Personally I wouldn’t touch any GSK drug with a barge pole..

TAF

http://www.townsvillebulletin.com.au/news/families-call-for-answers/news-story/b16483a5d4cb1318678f95d881037ec0

“…Through post-trial ­research, the ADF has confirmed mefloquine can cause side effects likened to that of PTSD, including agitation, mood swings, panic attacks, confusion, hallucinations, aggression, psychosis and suicidal thoughts in a small number of patients.

But Dr Remington Nevin, a leading international expert on mefloquine and tafenoquine, told the audience via Skype that the “information in the ADF consent forms undermined critical manufacturer’s safety information and understated known risks”.

He also said ADF subjects were not given information to allow for fully informed ­consent, attributing both failures to soldiers “experiencing lasting harm from the drug”.

AVM Smart the forum was a “step in the right direction” and provided important ­dialogue to inform “the next steps”.

“It was really beneficial to be able to listen and understand the experiences of those who attended so we can work on further reducing the barriers both current and ex serving members might encounter when trying to seek help,” she said.

The Department of Veterans Affairs declined to attend the forum….”

 

 

 

Check out the following links on

GSK’s Tafenoquine And Roche’s Mefloquine:

http://internationalmefloquineveteransalliance.org/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847738/

https://www.muckrock.com/foi/united-states-of-america-10/documents-referencing-the-neurotoxicity-of-tafenoquine-12940/

 

http://www.townsvillebulletin.com.au/news/side-effects-of-two-drugs-used-during-defence-trials-to-be-discussed-at-national-health-seminar/news-story/dee50f15e495d143cc12dcf24d93a7d0

http://researchonline.jcu.edu.au/29749/

https://twitter.com/RemingtonNevin

http://us.gsk.com/en-us/media/press-releases/2014/gsk-and-mmv-announce-start-of-phase-iii-programme-of-tafenoquine-for-plasmodium-vivax-malaria/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847738/

Lariam762012-veterans-against-lariam-protests-390x285

Mosquirix: GSK’s new Malaria Vaccine? .. Will it be safe?


GSK are heavily promoting their new Malaria vaccine, Mosquirix, at the moment, and of course the press are gushing sycophantic praise for it by the bucket-load. It has just been approved in Europe but personally, I’d take my chances with Malaria rather than take any GSK product. They just can’t be trusted to produce safe drugs because their safety record leaves a hell of a lot to be desired.

For example, their flu vaccine, Pandemirix, which was heavily touted for the (media generated) flu-scare a few years ago, has been shown to be extremely dodgy indeed, and many patients are now suing GSK because they have developed Narcolepsy because of this vaccine. Then of course we have the two most notorious GSK drugs of recent times, the killers – Seroxat (a dangerous anti-depressant which induces suicide) and Avandia (a diabetes drug which causes heart attacks)- the death toll, and scale of human misery, from those two drugs alone easily reaches into the hundreds of thousands.

Not forgetting of course, GSK’s Myodil dye, which has caused immeasurable pain and damage to tens of thousands of people for decades. Even with the GSK drugs which aren’t killers, GSK’s track record of inflating the positives, and hiding the negatives, when it comes to side effects, and clinical trials, is well known in the industry and beyond.

Their 3 Billion dollar fine with the department of justice consisted of a couple of hundred pages of various unethical shenanigans with various drugs over the years, and this is only the skullduggery that they were caught doing, imagine what they really get away with? They don’t call GSK, the “GLOBAL SERIAL KILLERS” for nothing, you know what I mean?

Mosquirix, no thanks.. I’ll take my chances with Malaria..

Because at least with Malaria, you know what you’re getting…

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