“I will never get my father back”: How the neurotoxic U.S. Army antimalarial drug tafenoquine destroyed the lives of countless Australian service families

It’s not fair on them, to grow up and have a parent have to go through this. I’ve destroyed not just my life. Everyone around me really. All for the sake of some trial drug I was made to take.

Mr Aaron King, Australian Army “Study 033” tafenoquine trial subject

THIS post highlights the devastating impact that tafenoquine has had on hundreds of the families of soldiers who where subjected to the notorious Australian Army Malaria Institute (AMI) drug trials in Bougainville and East Timor at the turn of the century.

Aaron King was one of 492 tafenoquine subjects in the AMI Study 033, involving a total of 654 soldiers from the 1st Battalion, the Royal Australian Regiment (1 RAR) while deployed on peacekeeping duties in East Timor in 2000-2001. Prior to the deployment, the soldiers were given “loading doses” of 600 mg tafenoquine, then 200 mg weekly for the rest of their seven month deployment. Despite the experiences of Aaron and many of his fellow soldiers, the trial report eventually published in 2010 did not include a single severe neuropsychiatric event report. For this and other reasons, the published report is believed to be fraudulent.

This was one of a series of tafenoquine drug trials undertaken by the Australian Defence Forces as part of a commercial agreement with the pharmaceutical industry which a former Director of the U.S. Walter Reed Army Institute of Research (WRAIR) conceded was “naive” and “desperate.” Tafenoquine is a product of the same WRAIR antimalarial drug discovery program as mefloquine. Both drugs are known to be neurotoxic. Despite the concerns of hundreds of the drug trial subjects like Aaron, the U.S. Army Medical Materiel Development Activity (USAMMDA) continued to commercialize the drug, in a contract with 60 Degrees Pharmaceuticals worth $18+ million, until in 2018 it was granted regulatory approval as Arakoda® in the U.S. and Kodatef® in Australia.

During last year’s Australian Senate Inquiry into the AMI drug trials, more than 100 written submissions were made by the participants or their families, while dozens testified in person at hearings held across the country. Below is the full written submission from Aaron’s daughter, Ms Angela King. Mrs Raelene King’s written submission is here and a transcript of her oral testimony is here. Included below is a video she made while preparing her written submission.

My name is Angela King,

I am writing to you about my Father Aaron King who was given Tafenoquine.

As a young girl growing up I had a great life. I loved going to the park and kicking the soccer ball with my dad. My dad was always there to read me stories before bed, help me with my homework and on certain nights we would have a game of Yahtzee.

I remember my dad joining the army, it had always been his dream and he used to talk it about with so much pride. I remember him loving his job, he wasn’t home much but when he was he always had time for me.

Things changed when he came back from East Timor in 2001. My dad left to go overseas to fight for our country and never came back.

What did come back was the shell of him, but he wasn’t inside, he wasn’t my dad. 

It wasn’t until 2017 that I leant he was given a drug called Tafenoquine and after reading about it, everything that was happening with my dad made sense. This wasn’t PTSD, this was poison.

I might have only been 6, but I remember like it was yesterday. My father turned to alcohol to cope, he was rarely home and this affected me deeply.

He was constantly in and out of hospital and rehabilitation centres, and still is to this day. I was lucky to have such a strong mother, but I grew up a lot faster then what I should have, having to help my mum with my younger siblings while dad wasn’t around.

I was put into counseling at the young age of 10. I was depressed, and had bad anxiety as I was constantly walking on eggshells waiting for the bomb to blow. 
I left home at the age of 15. I struggled concentrating in school as I was always worrying about what was going on at home and always had the fear of getting a call to say my dad had taken his life.

I could never understand why my dad was the way he was. I researched a lot about PTSD over the years. I knew everything about it, but with my dad deteriorating I knew there was more to it.

After dad having more hospital admissions I was still struggling to cope and turned to drugs. Still to this day i struggle with my own mental issues as a result of the way he is. 17 years later there has been minimal improvement with his mental state. I have read up a lot about the drug he was given, and read many stories that others have shared, and I know deep in my heart the drug Tafenoquine is to blame for making him like this.

I will never get my father back that I knew as a young girl, and every girl needs their father.

He was mistreated and used as a guinea pig along with many other people who served out country.

Is this your way of saying thank you for keeping our country safe?

By leaving them like this without any help or explanation?

Yours Sincerely,

Angela King

Over the coming weeks, we will continue to post more testimonies like these, highlighting not only the personal impact of tafenoquine on the affected service personnel and their families, but the systematic fraud, abuse and corruption which paved the way for this drug to be approved by drug regulatory agencies including the FDA and the Australian TGA.

“There is blood on the hands of the Army Malaria Institute,” says retired Australian Army Warrant Officer and tafenoquine test subject

“THE fraud and corruption involved in these [tafenoquine and mefloquine] drug trials is huge,” said retired Australian Army Warrant Officer Colin Brock in his testimony to a 2018 Senate inquiry hearing in the northern Queensland garrison city of Townsville. “The lying and deceit is incomprehensible.”

Warrant Officer Colin Brock, serving in Afghanistan

In today’s post we return to the Australian Army Malaria Institute’s (AMI) notorious clinical trials of tafenoquine in Bougainville (Papua New Guinea), East Timor and Australia at the turn of the century. As part of a commercial arrangement with the pharmaceutical industry which a former Director of the U.S. Walter Reed Army Institute of Research (WRAIR) described in 2018 as “naive” and “desperate”, the Australian Defense Forces subjected almost 4,000 troops to a series of highly controversial antimalarial drug trials considered to have been “manifestly unethical.”

One of these trials was the AMI “Study 033” for tafenoquine vs mefloquine prophylaxis involving a total of 654 Australian troops from the Townsville-based 1st Battalion, the Royal Australian Regiment (1 RAR) and supporting units. Among the 1 RAR battalion group soldiers deployed to the East Timor UN peacekeeping mission for seven months in 2000-2001, 492 were given the experimental drug tafenoquine, while a further 162 were given mefloquine.

Eight years after this trial, scientists from WRAIR (which developed both drugs) found that “tafenoquine is the only antimalarial more neurotoxic than mefloquine,” a drug from the same quinolines family, widely regarded as a suicide pill.

Mr Brock’s 20-year Army career included operational deployments to Somalia, East Timor and Afghanistan. During the East Timor peacekeeping deployment, then Corporal Brock commanded a mortar section of nine soldiers. He was one of dozens of drug trial subjects who testified to the Senate inquiry, and one of more than a hundred who made written submissions. Here are some highlights from his hard-hitting testimony, which can be found in full here.

At the beginning of the year 2000, 1 RAR was warned out for deployment to East Timor. I was a section commander in Mortar Platoon, Support Company. My section consisted of nine men, including me.

I am not sure of the specific date—I think it was sometime in September 2000—a battalion parade was held on the main parade ground of 1 RAR. We were formed up in companies and the commanding officer, Lieutenant Colonel John Calagari, briefed the battalion on a new malaria drug or drugs that we all were to take to prevent malaria. We were told that it was a trial to benefit the Defence Force. I now know the drugs to be mefloquine and tafenoquine. Lieutenant Colonel John Calagari then informed the battalion, ‘This drug is voluntary, but if you do not consent to take this drug, you will not deploy to East Timor.’ I can categorically state, 100 per cent, that he did say this. There was numerous talk about it after the parade. No-one in the battalion was going to say, ‘No, we won’t take it,’ as everyone wanted to deploy. If you knew about the Army culture, that is what you would want to do. If we knew of the consequences of these drugs, I and a lot of others would have told them to find someone else.

In my later years in Defence, I knew there was something not right with me. I thought it might have been PTSD, as I’d completed numerous deployments to some of the worst countries on Earth, but it was something else. My hearing was failing. There was ringing in my ears. I was having dizzy spells; vertigo issues, which I still have today; bouts of depression and anxiety; and anger issues. But, like a lot of people in Defence, you just put up with it. I loved being deployed, and nothing really fazed me.

I think it was in March 2016 that a forum was held at the Townsville RSL, which I attended with a number of other people who were severely affected by these drugs. A number of dignitaries attended, with key speakers and subject matter experts. Defence was represented by Air Vice Marshal Tracy Smart, Commander Joint Health. I have no words for Tracy Smart. All she did was deny any wrongdoing by Defence, saying the drug trials were conducting morally and ethically, and there was nothing wrong with us. She had no answers for us, just denial. One of my close friends, Chris Styles, had an open argument with her at the forum which was captured on visual and audio. Chris committed suicide less than two months later. Tracy Smart is a Defence toe-the-line person. She is fully aware of these drugs and does not care.

In May 2016, I was contacted by Brigadier Andrew Dunn as part of the IGADF inquiry into allegations of unethical and unlawful use of antimalarial drugs in Defence. This was a phone interview which lasted around 90 minutes. I answered truthfully all the questions asked of me. I have a clear recollection of these events, and one in particular. The main question I was asked was: what did Lieutenant Colonel John Caligari say on the parade ground as to the drug being voluntary? I answered: ‘John Caligari said, “The drug trial is voluntary, but if you do not consent to the trial you will not deploy to East Timor.”‘ As I said, I am 100 per cent correct that I heard this. I would not lie about this. I know the man’s reputation is at stake; I would not lie.

I received the findings for my part in this inquiry a while later. The report suggests that I basically lied to the inquiry—and so did four or five others that were with us—finding that John Caligari had never said those words. I was gobsmacked. He was an officer I respected, trusted and looked up to, as I had worked for him again in later years. He categorically denied it. There are hundreds of people from that 1 RAR parade ground who will agree with me. We are not liars. What would I have to gain by saying this? Nothing. Also, if you look at submission No.80, I don’t know if you have that with you, what he’s said in there—I saw that the other day in the submissions—is what I’m saying.

Everyone affected by these drugs wants answers. My section in East Timor consisted of nine fit men. Six out of the nine are now experiencing all of these symptoms and are unable to work; that’s a 75 per cent ratio. Why were Defence used as guinea pigs? Why were we forced to take these drugs? What do we have to do to get help—more suicides? There is blood on the hands of the malaria institute, Defence and the leaders of these so-called trials. I personally have been to two funerals as a direct result of these horrendous drugs, and it will keep happening. Just three days ago a former member of 1 RAR who was on these trials committed suicide. That was three days ago. It’s still happening. The fraud and corruption involved in these trials is huge. The lying and deceit is incomprehensible. People and organisations need to be held accountable for the damage they have done to hundreds if not thousands of officers and soldiers.

This is the first in a series of posts highlighting the testimonies of some of the thousands of ADF personnel who were subjected to these drug trials, which have been described as “the most shameful chapter in the recent history of the ADF.” Over the coming weeks we will post more of these first hand testimonies, from the subjects of the unethical drug trials which provided much of the basis for the 2018 regulatory approvals of Arakoda® in the US and Kodatef® in Australia. The evidence we already have is sufficient to prove that the official report from Study 033 and some of the other AMI tafenoquine trials are fraudulent.

Senior U.S. Army medical officer who previously raised doubts about the safety and efficacy of tafenoquine retires, gets job with drug manufacturer after landing them an $18+ million government contract

Changes in tafenoquine CYP 2D6-mediated clearance could potentially exacerbate any parent molecule-mediated toxicity despite drastically reducing its liver-stage efficacy mediated through CYP 2D6 metabolism.

The tafenoquine-CYP 2D interaction is also problematic due to the likelihood of CYP 2D6-mediated drug-drug interactions in humans with other antimalarial drugs and commonly prescribed medications.

Colonel Bryan Smith and colleagues, Differential Cytochrome P450 2D Metabolism Alters Tafenoquine Pharmacokinetics, 2015

RECENTLY retired U.S. Army Colonel (Dr) Bryan Smith is among a group of military doctors and scientists from the Walter Reed Army Institute of Research (WRAIR) and the U.S. Army Medical Materiel Development Activity (USAMMDA) who raised serious concerns about the safety and efficacy of tafenoquine, in a series of papers published in scientific journals from 2013 to 2015.

The papers began to be published four years after scientists at WRAIR discovered – in laboratory studies uncovered through FOIA requests by retired U.S. Army Dr Remington Nevin – that tafenoquine “is the only antimalarial more neurotoxic than mefloquine.” Tafenoquine is from a class of 8-aminoquinoline antimalarials which were originally discovered to have been neurotoxic during a WWII-era drug discovery program, on par with the Manhattan project in terms of scientific scale, which found more than 85 of these drugs caused lasting or permanent brain damage in primates subjected to pre-clinical safety testing. For safety reasons, these highly dangerous drugs were then excluded from the clinical testing program which ultimately led to the introduction of primaquine, the standard P. vivax malaria treatment drug for the past six decades.

The papers by Colonel Smith and his colleagues examine the role of the Cytochrome P450 2D6 (CYP2D6) enzyme in metabolizing the 8-aminoquinoline drug primaquine and it’s newer analogue tafenoquine. The studies were undertaken as part of the late-stage tafenoquine drug development process, almost 15 years after tafenoquine was tested on 1,540 Australian peacekeeping troops in a series of notorious drug trials in Bougainville (Papua New Guinea) and East Timor.

The devastating impact of the Australian Army tafenoquine drug trials

CYP2D6 is known to metabolize a quarter of all clinically used drugs and plays a key role in drug safety, efficacy and drug-drug interactions. For people with reduced CYP2D6 function, representing up to one third of some populations, certain drugs can be ineffective and/or dangerous. Additionally, many drugs can inhibit CYP2D6 function, resulting in dangerous drug-drug interactions. One such drug is chloroquine, another quinoline antimalarial which has commonly been co-administered with primaquine in the treatment of P. vivax malaria.

The papers cast serious doubts about the safety, efficacy and hence the commercial value of tafenoquine. In January 2018, researchers from GlaxoSmithKline (GSK) and Oxford University published the results of a large-scale clinical trial comparing tafenoquine to primaquine in the treatment of P. vivax malaria, which found both drugs failed to treat the serious disease in more than a quarter of patients.

The U.S. FDA and Australian Therapeutic Goods Administration had approved tafenoquine several months earlier. Australian neurotoxicologist Professor Jane Quinn and retired Australian Army Major Stuart McCarthy, responded to the GSK/Oxford study in the New England Journal of Medicine, raising further serious doubts about tafenoquine:

Although the participants in the trial by Llanos-Cuentas et al. were not all screened for CYP2D6 status, Baird et al. recently estimated that 38.8% of the population living at risk of P. vivax infection are unable to receive safe and effective primaquine therapy because of glucose-6-phosphate dehydrogenase (G6PD) deficiency and reduced CYP2D6 function. We therefore recommend that CYP2D6 allelotype screening be included in future clinical studies of tafenoquine to address unresolved safety and efficacy concerns before this drug is widely used for P. vivax eradication or prophylaxis in travelers worldwide.

The 8-aminoquinoline/CYP2D6 papers were published while Colonel Smith was the product manager for tafenoquine at USAMMDA, the U.S. Army agency responsible for medical product commercialization and approval. During this period, Colonel Smith oversaw the contractual work of Australian expatriate Dr Geoffrey Dow, a former U.S. Army employee who in 2010 founded his own company, 60 Degrees Pharmaceuticals (60P), then in 2014 was awarded the U.S. Army license for tafenoquine as part of an $18+ million contract to register the drug in the U.S. and Australia. The following year, 2015, Dr Dow stated that his motivation in seeking FDA approval for tafenoquine was to obtain a “priority review voucher” valued at up to $350 million.

USAMMDA promotional video including the tafenoquine U.S. FDA approval celebration in 2018

According to Colonel Smith’s written testimony to a 2018 Australian Senate Inquiry, he retired from the Army at the end of 2015 then immediately began employment with the pharmaceutical consulting firm Clinical Network Services (CNS). Since that time, he has also been employed as the 60P chief medical officer.

Since January 2016 I have been employed full-time as the Principal Medical Consultant for Clinical Network Services. Within this role I am contracted to also operate as the Chief Medical Officer for 60 Degrees Pharmaceuticals. Other than my salary as an active duty officer in the U.S. Army, my current Army retirement pay, and my current salary as Principal Medical Consultant for Clinical Network Services (CNS), I have received no other compensation of any kind for the work I have performed for USAMMDA, CNS, or 60 Degrees Pharmaceuticals.

Colonel Bryan Smith (retired), testimony to Australian Senate inquiry, 2018

After Colonel Smith had commenced his lucrative post-Army career at CNS/60P, three of his former U.S. Army colleagues co-authored a 2016 “current state of the art” paper on CYP2D6 primaquine metabolism with findings that have since been confirmed in a breakthrough study published in a July 2019 edition of Nature Communications, one of the world’s most prestigious scientific journals. The 2016 Marcsisin, Reichard & Pybus paper also made some highly significant conclusions for the commercial viability of tafenoquine (emphasis added):

In addition to addressing the questions raised above, there is a need for the development of liver stage/radical curative antimalarial drugs that do not require metabolism by polymorphic CYP enzymes. Currently, there are no drug candidates in the drug development pipeline that are radical curative that do not seem to require hepatic metabolism. The only other 8-aminoquineoline that is close to fielding and under late stage development for radical cure is tafenoquine. Tafenoquine is a single dose radical curative agent that is a promising alternative to primaquine, however, tafenoquine might also require hepatic metabolism for efficacy as indicated by pre-clinical testing in animal models. … there is a need for the discovery and development of new safer antimalarial agents that treat relapsing strains of malaria and do not require CYP 2D6 metabolism for activity.

This is the first in a series of posts about the dealings of Colonel Smith, Dr Dow, 60 Degrees Pharmaceuticals and their associates. Although Smith and his associates have denied any wrongdoing, in subsequent posts we will dig deeper into this aspect of a story that bears all the hallmarks of yet another pharmaceutical industry corruption racket.

Senior Australian Army doctor accused of culpability over the deaths of tafenoquine and mefloquine drug trial subjects

Australian Army Major Stuart McCarthy in 2015

Vice Admiral Griggs cannot wash his hands of this, try as he might. The ADF caused it, to our eternal shame. The AMI and the authors of those drug trial reports—among them the ADF’s director of military medicine, Colonel Leonard Brennan—bear direct responsibility for those deaths and the legacy of widespread chronic illness among coalition troops. 

Major Stuart McCarthy, testimony to Australian Senate inquiry, 2015

IN Bougainville and Timor, army medical officers also prescribed a drug known as tafenoquine to 1512 troops, even though it had not — and still has not — been approved for use by Australian authorities.

A series of allegations have now been made about the ethics of these trials and the impact they may have had on the mental health of the participants.

One serving army officer who took mefloquine, Major Stuart McCarthy, alleges the trials were “manifestly unethical” because officers compelled soldiers to take the drug without properly warning of the risks.

He’s supported by a US expert who believes the ADF trials were “deeply unethical”.

McCarthy alleges one commanding officer of troops headed for Timor told his men they would not be deployed unless they took part in the trial, which McCarthy says amounts to compulsion.

In evidence to a Senate committee last week, McCarthy named the ADF’s director of military medicine, Colonel Leonard Brennan, as having “direct responsibility” for the chronic illness and death of Australian and allied troops. Brennan is mentioned in academic journals as having been part of the “study team” that tested tafenoquine and he has co-authored articles about the testing of both drugs on soldiers.

Source: Paul Cleary, “Drug trial a test of ethics,” The Australian, September 11, 2015