“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.

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.

Australian Army poisons one of its officers with tafenoquine then continues to use him in their recruiting ad campaign

With the deployments to East Timor and Bougainville, over 3,000 Australian soldiers were subjected to these quinoline drugs, as part of a trial through the military. We’ve assessed through the Department of Veterans’ Affairs own statistics that about 1,000 of the people who were subjected to these drugs have been diagnosed with severe mental health disorders like post-traumatic stress disorder.

Retired Australian Army Captain Andrew George, Sky News Australia, June 6, 2018

ANDREW George was one of the 1,540 Australian Defense Force (ADF) personnel given tafenoquine during the Army Malaria Institute’s notorious quinoline drug trials which involved more than 4,000 troops in Bougainville (Papua New Guinea), East Timor and Australia from 1999 to 2002. The ADF has since admitted that it did not subject tafenoquine to appropriate neurotoxicity testing on primates either before or after these clinical trials. In 2009, scientists from the U.S. Walter Reed Army Institute of Research, which developed both tafenoquine and mefloquine, conducted laboratory studies which found “tafenoquine is the only antimalarial more neurotoxic than mefloquine.”

Like many of the other tafenoquine trial subjects, Andrew was subsequently discharged from the ADF and continues to experience severe, chronic ill-health consistent with quinoline poisoning, against a wall of denials from senior ADF officials including the Surgeon-General, Air Vice Marshal Tracy Smart. Through all this, the ADF continued to feature Andrew in their Army Reserve – Challenge Yourself recruiting campaign on billboards, brochures and television.

Tafenoquine was granted regulatory approval by the U.S. Food and Drug Administration and the Australian Therapeutic Goods Administration in 2018. The FDA approval entitled GlaxoSmithKline to a “priority review voucher” which can be sold on the open market for hundreds of millions of dollars, even if a single tablet of the drug is never sold.

“Andrew George, a former infantry soldier and public relations officer with the Army Reserve, was treated with tafenoquine in Sydney and claims it left him with damaging side effects.

“Mr George, who features in promotional material for the reserves, said he was given the drug after being diagnosed with malaria but does not recall giving informed consent after a detailed explanation of the drug.

“He is one of many veterans seeking answers about the drugs with many believing it complicated their diagnosis and management of post-traumatic stress-disorder.”

Source: Henry Belot, “Therapeutic Goods Administration warned military doctors before using experimental drug on soldierssoldies,” Sydney Morning Herald, April 29, 2016

How U.S. Army officials got played by GlaxoSmithKline into subjecting 1,540 Australian peacekeeping troops to tafenoquine drug trials for commercial purposes

Walter Reed Army Institute of Research, Silver Spring MD

CONTRADICTING recent claims by Australian Defense Force (ADF) Surgeon General Air Vice Marshal Tracy Smart that a malaria outbreak during the early stages of the East Timor deployment in 1999-2000 necessitated the use of the experimental drug tafenoquine, a former WRAIR director has stated that the U.S. military was looking for large numbers of allied troops able to participate in clinical trials as part of its commercial arrangements with GlaxoSmithKline (GSK).

We essentially said: ‘We have developed [tafenoquine] to the point at which we cannot develop it any further. We need an industrial partner. You [GSK] develop it and make it available to us.’

We were completely naive, because we were desperate.

We were very mission driven, very altruistic, really babes in the woods when it came to business and such, and it showed, right? We routinely got taken advantage of, and didn’t understand the operating environment.”

FORMER WRAIR DIRECTOR, 2018

A 1998 Australian Army Malaria Institute (AMI) clinical trial in Bougainville had previously found another GSK drug, Malarone (from another drug class), to be as effective against malaria (less P. vivax eradication) and better tolerated than the existing ADF first line drug doxycycline. AMI recommended against the adoption of Malarone due to cost, less than the cost of a cup of coffee per day. Regardless, Malarone replaced mefloquine as the ADF’s second line antimalarial in 2006, when the latter drug was relegated to “drug of last resort” due to the risk of neuropsychiatric side effects. Malarone is now regarded as so safe that it is sold over the counter (without prescription) in many countries.

AVM Smart’s claim that the P. Vivax malaria outbreak most likely resulted from “drug resistance”, or “poor compliance” with the standard primaquine post exposure prophylaxis (PEP) regimen, has also been largely debunked in some of the world’s leading medical-scientific journals. Throughout the history of the use of primaquine, a significant proportion of individuals have contracted P. vivax malaria despite compliance with the recommended dose regimen. Drug failures have typically been mis-attributed to “poor compliance” or assumed “drug resistance” in the malaria parasite. However there has never been any direct scientific evidence of P. vivax resistance to primaquine. This has only ever been an assumption.

In recent years, leading malaria research scientists have discovered that the 8-aminoquinolines (including primaquine and tafenoquine) are largely ineffective because they need to be metabolised by an enzyme known as CYP2D6. Up to one quarter of the population carry a genetic deficiency which means they remain at risk of contracting malaria even if they are fully compliant with the prescribed drug regimen. In allowing the U.S. military to subject 1,540 of their soldiers to these drug trials, senior ADF officials switched from a largely ineffective but relatively safe and registered drug, to very high doses of an equally ineffective but unregistered drug which is also known to be neurotoxic.

Some time around 2010, coinciding with the publication of AMI Study 033 (the 1 RAR tafenoquine prophylaxis trial in East Timor), GSK discontinued it’s involvement in developing tafenoquine for malaria prophylaxis, ostensibly due to safety concerns for G6PD-deficient individuals. The GSK drug indicated for the treatment of P. vivax malaria, based on a single 300 mg dose sometimes called “radical cure” is known as Krintafel® in the U.S. or Kozenis® in Australia. Regulatory approval of Krintafel® by the U.S. Food and Drug Administration in 2018 entitled GSK to the award of a “priority review voucher”, a saleable product valued at up to USD$350 million, even if a single tablet of this drug is never sold.

Further background is available here and here.