Current, former ADF members implicated.
Pharmaceutical concerns on two continents involved. Fraudulent studies used to obtain regulatory approvals.
Hundreds of millions of dollars, tens of thousands of lives at stake.
An investigation has revealed that a massive fraud and corruption scandal could soon erupt in Australia and North America. At issue is the recently approved anti-malarial drug tafenoquine, as evidence shows that regulatory processes were obfuscated and the drug was approved under fraudulent circumstances. Many of the people involved are current or former members of the Australian Defense Forces as well as at least one former member of the United States Army. The people implicated have had or currently occupy senior positions in the ADF, and could go even higher yet.
The Caligari Brief
I received a copy of a brief to Lt.Gen. (ret.) John Caligari of the Australian Defence Forces that is dated December 20th, 2017. It is in relation to his capacity as the head of the Operation COMPASS Steering Committee in Townsville, a group committed to preventing suicide among ADF veterans. Its contents are explosive and the author wished to remain anonymous, however this person is a former senior officer in the ADF with direct knowledge of the situation.
Purpose 1. This brief requests your assistance for Australian veterans who have been adversely affected by drugs given to them as part of the Army Malaria Institute (AMI) drug trials conducted in Bougainville and East Timor during the period 1998-200 1. Your help is now urgently needed as recent developments internationally have brought one of these drugs, the antimalarial drug ‘tafenoquine’, a step closer to registration.
Importance 2. Why is this so important? Tafenoquine has caused serious long-term adverse health effects in a proportion of veterans who were exposed to this drug as part of military and pharmaceutical industry-funded clinical trials in the United States and Australia. These veterans have not been properly compensated or had their health conditions accepted by the Commonwealth, yet senior Defence of ficials have already stated that they will adopt tafenoquine as a key antimalarial drug for ADF personnel once the drug is registered in Australia. This is despite poor evidence of safety and appears only due to the involvement of the ADF in bringing this drug to market.
The Present Danger 3. The developers of tafenoquine have recently applied to United States and Australian health authorities for regulatory approval. The results of the AMI tafenoquine trials, particularly the East Timor 1 RAR trial in 2001 (“Study 033”), are being cited in support of these applications to justify tafenoquine as a safe and effective antimalarial drug, despite strong evidence to the contrary. Evidence of ill-effects that have been presented to the drug manufacturer GlaxoSmithKline (GSK) by our group have been submitted to the FDA as part of the GSK registration package, acknowledging that long-term health effects have been caused by exposure to tafenoquine for those involved in the AMI trials. Despite this acknowledgement by the drug manufacturer, the Departments of Defence and Veterans Affairs continue to deny a causal relationship.
Brief for Lieutenant General (ret.) John Caligari AO, DSC Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug Tafenoquine
The bottom line here is that faulty and inaccurate data was presented to the FDA in an effort to get tafenoquine approved. An effort had even been put forth to have the approval granted expeditiously. The FDA was not informed of the numerous reports of adverse rections to the drug, which would have likely at the very least delayed approval but more likely would have resulted in a rejected application.
Institutional Denials Both Defence and DVA leaders have been informed of the serious health issues experienced by the Bougainville and East Timor drug trial veterans. They have failed to fund any investigation into these cases, despite proposals being submitted to them on a number of occasions, and after their requests for us to make those proposals. Worse, in late 2016, senior Defence leaders prevented any retrospective investigation occurring into the health outcomes for these veterans by placing restrictions on data access which deny researchers access to any past trial data for these and other ADF trial cohorts . The ethical and intellectual ramifications of this action are still in dispute with senior Defence officials by the key Defence and DVA research providers, with no acceptable outcome to date despite Ministerial intervention. Senior Defence officials have ‘shut down’ research into this question.
Brief for Lieutenant General (ret.) John Caligari AO, DSC
This is simply unethical.
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
This is fairly self-explanatory.
The Risk Should tafenoquine be approved by drug regulators, there is a likelihood this drug will cause extensive harm to ADF members, including loss of life. This has already occurred with its counterpart mefloquine over the past three decades. We do not want to see the same situation repeated. A clear statement of support is needed now, to prevent further harm to ADF members and their families in future.
Brief for Lieutenant General (ret.) John Caligari AO, DSC
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
There is clear and convincing evidence that tafenoquine has harmed a number of ADF personnel, even contributing to a number of deaths, and that it is more neurotoxic than mefloquine.
Detailed Background Tafenoquine is an experimental quinoline drug which was initially developed by the US Walter Reed Army Institute of Research (WRAIR) and is manufactured by GSK. The AMI trials were conducted in close cooperation with WRAIR and GSK, involving a total of 1,540 ADF tafenoquine subjects (including 492 personnel from the 1 RAR BG in Study 033), to investigate the safety and efficacy of tafenoquine for prevention and treatment of malaria. A large proportion of those subjects have since suffered serious, chronic symptoms consistent with adverse neurotoxic effects common to a number of similar quinoline antimalarial drugs.
Despite continued development of tafenoquine since the AMI trials, and despite our repeated requests, there have been no follow up studies on this large cohort (comprising more than a third of the total number of individuals administered
tafenoquine worldwide to date) to assess the long term health risks of exposure to
this drug.In 2009, laboratory studies co-authored by WRAIR scientists found that
tafenoquine was “the only [antimalarial] drug more neurotoxic than mefloquine”. Mefloquine is known to be able to cause “lasting or permanent” brain damage at standard malaria prevention dosages comparable to the tafenoquine dosages used in Study 033. The symptoms of this brain damage are commonly mistaken for PTSD and other neuropsychiatric disorders.Few if any of the AMI trial subjects adversely affected by tafenoquine (or mefloquine) have been provided with appropriate or effective specialist health care. Typically, those seeking help have been diagnosed and treated for PTSD or other psychiatric disorders, then subjected to ineffective and/or harmful treatments including antipsychotic drugs and electro-convulsive therapy (ECT). Unemployment, self-harm and family breakdown have been common, as well as cases of homelessness and suicide.
Brief for Lieutenant General (ret.) John Caligari AO, DSC
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
Not only has it made ADF personnel sick, but those personnel are not receiving the proper treatment, which can have fatal results.
In 2014, WRAIR found that tafenoquine needs to be metabolised by the CYP2D6 enzyme in order for it to work against the malaria parasite, i.e. it does not work against malaria for individuals who have reduced CYP2D6 function, which is very common (e.g. in the range of 12-23% of Caucasians). A number of the AMI tafenoquine trial subjects who contracted vivax malaria despite supervised, documented compliance have since paid for their own CYP2D6 tests to find that they have reduced CYP2D6 function. Individual variation in CYP2D6 metabolism is also one of the possible explanations as to why only a certain proportion of individuals are susceptible to quinoline neurotoxicity.
Our own research has found that ALL individuals who report significant
Brief for Lieutenant General (ret.) John Caligari AO, DSC
long-term health issues that can be causally linked to being administered
tafenoquine during the AMI trials are of a CYP2D6 metabolism type which makes
this drug both ineffective as an antimalarial and potentially toxic at normal treatment levels. This information has been passed to both the ADF and GSK. The ADF has ignored the potential ramifications of these findings. GSK acknowledged that they are aware of the risks for CYP2D6 poor metabolisers and were ‘surprised’ we had come to the same conclusion.
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
Put simply, about 25% of the people who take tafenoquine will NOT be protected against malaria and will get it regardless. Not only that, but the chances are greater that you will end up with brain damage as a result of taking this drug than if your took mefloquine, which already carries an unacceptable risk of brain damage.
Since the AMI trials at the turn of the century, the development of tafenoquine
Brief for Lieutenant General (ret.) John Caligari AO, DSC
has continued as follows:
a. GSK has continued to develop tafenoquine for the single dose treatment (aka
“radical cure”) of vivax malaria, in collaboration with the Medicines for Malaria
Venture (MMV). The current AMI Director, Professor Dennis Shanks, is a
member of the MMV scientific advisory committee. GSK recently announced that it has applied to both the US Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) for regulatory approval.
b. 60 Degrees Pharmaceuticals (60P), a company established by former US
Army employee Dr Geoff Dow in 2010, has continued to develop tafenoquine for malaria prevention in collaboration with the US Army and individuals from AMI (specifically, Professor Shanks). 60P recently announced that it has applied to the FDA for regulatory approval and we anticipate that it will soon (if not already) make a similar application to the TGA.
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
This is where the confusing and convoluted conflicts of interest begin. Be forewarned, you are about to enter a nightmarish set of interconnected relationships that will leave you with a headache at the end of it. That being said, it will all make sense.
60P is attempting to downplay the importance of CYP450 phenotyping for
Brief for Lieutenant General (ret.) John Caligari AO, DSC
tafenoquine use as this would make an application for prophylaxis commercially
unviable.
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
If I could give someone considering taking tafenoquine any advice it would be this, don’t take it, but if you absolutely insist upon taking it, then when you go to your doctor for the Rx, ask for a blood test to check the levels of the CYP450 enzyme in your blood. If they are below a certain level you shouldn’t take it anyway, it will be dangerous to your health.
While we are concerned about the development of tafenoquine in general, we
are particularly concerned about the activities of 60P:
a. 60P was founded by Dr Dow while he was a contracted employee of the US
Army. Dow had previously been employed at WRAIR on antimalarial drug
research, then founded 60P while working on the development of tafenoquine
as a contractor for the US Army Medical Materiel Development Activity
(USAMMDA). Dow’s supervisor at USAMMDA was Colonel Bryan Smith, who
has since retired from the US Army and is now employed by Dow as the 60P
Chief Medical Officer. During this period, Dow/60P was awarded the US Army license for tafenoquine.b. In 2014, 60P was awarded a US Army contract to “assist in the development of
tafenoquine as a malaria prophylactic drug for FDA-TGA (Food and Drug
Administration-Therapeutic Goods Administration) approval first in Australia
and then in the United States.” Dow’s most recent tafenoquine paper indicates
that 60P continues to receive funding from the US Army for this purposec. In 2014, Smith was requested in writing to undertake follow up research on
the AMI tafenoquine subjects, involving a senior US military specialist doctor,
to investigate the drug’s long term adverse effects. Smith acknowledged this
request but declined to undertake the follow up research.d. In 2015, Dow stated in an interview that his motivation in registering tafenoquine was to obtain a US FDA “priority review voucher” (PRV), valued at up to several hundred million dollars. In a 60P media release of 18 December 2017, Dow states “It is our belief our dossier will receive priority review, expediting the review of tafenoquine, and 60P may qualify for a priority review voucher.”
e. Having previously declined to undertake follow up investigation of the long term adverse health effects of tafenoquine on the AMI trial subjects when
they were employed by the US Army, 60P employees continue to cite the
original AMI Study 033 findings in a 2017 “integrated safety analysis” paper
which provides the basis of their regulatory applications.f. The above situation reflects these comments by Professor Aaron Kesselheim
Brief for Lieutenant General (ret.) John Caligari AO, DSC
(of Harvard University) when he said of the FDA PRV system last year: “I think
it’s problematic and potentially dangerous to use this crucial process as a
lever to try to artificially create value for a for-profit company, even for an
area like neglected diseases that desperately needs more attention.”
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
I don’t know how many more ways this can all stink, and it’s also all about the money.
Since 2015 we have made repeated efforts to raise our concerns about the
safety and efficacy of tafenoquine in Australia and internationally, including but not limited to:
a. A Townsville health forum attended by senior ADF health of ficials, medical
experts and a number of the original AMI tafenoquine trial subjects.
b. Numerous meetings with Ministers and senior of ficials from the Departments
of Defence and Veterans Affairs.
c. A written proposal to the Minister for Veterans Affairs to fund a dedicated
program of outreach, rehabilitation and research for ADF veterans adversely
affected by tafenoquine and mefloquine.
d. Meetings with GSK representatives in Australia and the UK.
e. Written complaints to the TGA and the Minister for Healthf. Written complaints to the Australian Federal Police.
Brief for Lieutenant General (ret.) John Caligari AO, DSC
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
The matter has been taken to the federal police. What else can be said?
Despite these efforts, there has been no follow up investigation into the long term adverse health impacts of tafenoquine among the 1,540 AMI trial subjects and
our requests for a dedicated outreach and research program have been repeatedly rejected. During this period, senior ADF medical officials hav repeatedly misled Ministers, Parliamentary committees, the media and the ex service community. We believe that this misinformation has been intended in part to facilitate the successful registration of tafenoquine for the financial gain of 60P.In the event that tafenoquine is granted regulatory approval, we are also
Brief for Lieutenant General (ret.) John Caligari AO, DSC
deeply concerned about the serious distress among the AMI tafenoquine trial
subjects when they learn of the substantial financial gain to 60P after our requests for follow up research and medical have been repeatedly declined. In essence, many of these veterans and their families are begging to charity for health care while 60P stands to profit up to several hundred million dollars from the tafenoquine trials which caused so much harm.
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
Nothing needs to be said here.
Conclusion Given that the above concerns about the safety and efficacy of tafenoquine have thus far been ignored, and health authorities are now considering applications for registration, we are now requesting you to publicly support our calls for a dedicated outreach, research and rehabilitation program those affected. This would ensure not only that the Commonwealth fulfils it’s duty of care to the drug trial veterans and their families, but would also reduce the risk of unnecessary harm to ADF personnel who may be given tafenoquine in future.
Brief for Lieutenant General (ret.) John Caligari AO, DSC
Safety and Efficacy Concerns Regarding the Experimental Antimalarial Drug
Tafenoquine
The man in charge of overseeing the drug trials, Brig. Gen Leonard “Dr. Death” Brennan, once told someone that their efforts to see such a program put into place would end in frustration. This then raises the question of his involvement in this scandal, and now raises the possibility that Brennan could also have some conflicts of interest of his own going on here.
60 Degrees Pharmaceuticals
The lie printed in a news release.
60 Degrees Pharmaceuticals Fast Tracked For Malaria Drug
WASHINGTON, Jan. 4, 2018 /PRNewswire/ — 60 Degrees Pharmaceuticals (60P) has received Fast Track designation from the United States Food and Drug Administration (USFDA) for the investigation of Tafenoquine for prevention of malaria in adults.
60P entered into a cooperative research and development agreement with the U.S. Army Medical Materiel Development Activity (USAMMDA) in 2014 to develop Tafenoquine as a weekly prophylactic drug for the prevention of malaria. Since malaria is the top infectious disease threat to U.S. Military service members overseas, the military maintains a robust anti-malarial drug development effort through internal research and commercial partnerships.
NEWS PROVIDED BY
The NDA submission is a culmination of over 30 years of research and development with the U.S. Army Medical Research and Materiel Command, from the discovery of Tafenoquine at the Walter Reed Army Institute of Research through the current collaboration between 60P and USAMMDA.
A recent analysis of five clinical trials to assess the safety and tolerability of Tafenoquine has been published in Travel Medicine and Infectious Disease, a peer reviewed journal. The authors concluded that Tafenoquine appeared to be safe and well tolerated when the anticipated clinical regimen (ACR) was administered.
In all five studies, the majority of adverse events (AEs) were mild or considered unrelated to the study drug. For the full article, “Tafenoquine for malaria prophylaxis in adults: An integrated safety analysis,” by Moreno et al., 2017, please go to: http://www.travelmedicinejournal.com/article/S1477-8939(17)30079-0/fulltext
60 Degrees Pharmaceuticals Jan 04, 2018, 09:45 ET
There are some serious questions as to the ethics and legalities of the trials performed in Bougaineville and Timor Leste, study 033 in particular. It it this data that was used on the application to the FDA for fast track approval last year, which it received on July 20th, 2018 under the brand name Krinfantel. No mention was ever made of any of the adverse events that were reported, and the drug was made out to be reasonably safe.
A Letter to the Senate Foreign Affairs, Defence and Trade References Committee
This letter was sent by Karl Herz, Managing Director of a company called Biocelect Pty Ltd.
About Biocelect
Biocelect is a Sydney-based company that sources, in-licences and commercialises biopharmaceutical products for Australia, New Zealand and the South Pacific that address unmet medical needs of patients. In Australia, Biocelect has just registered its first specialty prescription product, KODATEF (tafenoquine), the first new drug molecule for malaria prevention in 20 years. Biocelect launched KODATEF (tafenoquine) in early 2019.
Thank you for the opportunity to provide evidence to the committee on 8 November 2018. I would like to provide some additional information to further clarify one area of my evidence on page 17 of the transcript and the sentence is highlighted below: Mr Herz: Biocelect would like to thank the committee for the opportunity to appear before you today. As an individual I feel and as an organisation we feel for the plight of the veterans and what they are experiencing and hope that they receive all the help that they need. During the hearings, I have observed the overwhelming amount of information presented to the committee from various sources. Whilst the veterans’ stories are harrowing, we believe that we need to respect the findings of the various regulators and their experts. We have been working with 60 Degrees Pharmaceuticals since 2013 on the commercialisation of tafenoquine, and we made a decision to license tafenoquine for malaria prevention for Australia and other countries in the region, the first new product in 20 years for malaria prevention in Australia.
Karl Herz, B. App. Sc. (Biomedicine) Managing Director Biocelect Pty Ltd
http://www.biointelect.com/our-people/
Knight Therapeutics
Canadian connection.
https://60degreespharma.com/investors/
HISTORY
2010: 60P established
2012: Secured $2 million in initial funding
2013: Established an Australian subsidiary to support global research projects
2014: Commercialization of tafenoquine for malaria prophylaxis initiated with U.S. Army
2016: Knight Pharmaceuticals provided $4 million in financing to support the 60P tafenoquine program
2017: 60P filed IND for tafenoquine with a target indication for the prevention of malaria
Overview Knight Therapeutics Inc. (TSX:GUD) is a publicly-traded, specialty pharmaceutical company focused on acquiring, in-licensing, out-licensing, marketing and distributing innovative prescription pharmaceuticals, consumer health products and medical devices in Canada and select international markets. In addition, Knight invests in or finances other life sciences companies with the goal of securing product distribution rights. Knight has acquired or in-licensed a portfolio of over 20 products that are marketed, under regulatory review or in various stages of development. Knight is headquartered in Montreal, Quebec, Canada and has over 45 employees.
https://www.gud-knight.com/overview/
Knight Therapeutics CEO: I made a mistake in selecting my partner
Jonathan Goodman, well known player in the Canadian pharmaceutical industry, has had a rocky last couple of quarters, and this news may not improve the overall outlook.
If tafenoquine is pulled from the market, Goodman and his company could be out $4 million. Ironically enough, the trouble Goodman seemed to be having stemmed from the fact that he wasn’t being enough of a risk-taker. Goodman may have risked it all on tafenoquine.
Investigation only just begun.
There is still a lot of investigating to be done, but one thing is abundantly clear to me, I’m not the only one that should be doing this. At this point there should be enough to warrant a commission of inquiry as well as investigations and hearings by the senate, the judiciary, and law enforcement.
Let me also be clear that all of the people implicated in this affair who were ADF personnel are senior or general officers. There is no evidence of complicity on knowingly doing wrong on the part of any junior officers or NCO’s of any rank. It is a pervsive cancer that appears to have run rampant through the upper echelons of the ADF, and as the investigations move forward the true scale of this scandal will become overwhelmingly apparent.
For now though, the investigation goes on.
The Advocate-Equalizer 
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