Since taking over as the product manager for our lead antimalarial drugs we’ve continued to work closely together on tafenoquine’s development program, with key attention being paid to how best to adequately and accurately address and potential central nervous system (CNS) toxicity liabilities that it may have.Colonel Bryan Smith, “Colonel Jennifer Caci USASOC request,” USAMMDA leaked email, February 10, 2014
LAST week we revealed how a recently retired U.S. Army Colonel – Dr Bryan Smith – raised serious concerns about the safety and efficacy of tafenoquine in a series of papers published in scientific journals from 2013 to 2015, before landing the Washington DC-based company 60 Degrees Pharmaceuticals an exclusive $18+ million government contract for the drug’s continued development.
Today we continue the story by revealing a series of leaked emails from Colonel Smith and his current boss Dr Geoff Dow – the CEO of 60 Degrees Pharmaceuticals – showing how Smith stonewalled a crucial follow-up safety study on injured Australian Army drug trial subjects, presumably to facilitate the drug’s FDA approval.
Tafenoquine is from a class of 8-aminoquinoline antimalarials which were 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. Eight years after tafenoquine had been tested on 1,540 Australian soldiers deployed on peacekeeping operations in Bougainville and East Timor, laboratory studies at the Walter Reed Army Institute of Research (WRAIR) found that tafenoquine “is the only antimalarial more neurotoxic than mefloquine.”
One senior Australian soldier who was subjected to the trials said to a 2018 government inquiry that “the fraud and corruption involved in these drug trials is huge.” In one of more than 100 written submissions to the inquiry, the daughter of another soldier subjected to the same trial wrote:
I will never get my father back … He was mistreated and used as a guinea pig along with many other people who served our country.
In 2014, Colonel Smith was the product manager for tafenoquine at the U.S. Army Medical Materiel Development Activity (USAMMDA) in Fort Derrick MD. USAMMDA is the organization which commercializes medical products developed by the Army, ensuring they are safe and effective prior to regulatory approval by the Food and Drug Administration (FDA).
A series of emails obtained from a source at USAMMDA now show that Colonel Smith was approached by military colleagues concerned about tafenoquine’s safety, to approve a follow-up study on a group of the Australian soldiers subjected to the notorious Australian Army drug trials at the turn of the century. The report of “Study 033”, which involved 492 tafenoquine subjects and 162 mefloquine subjects, published in 2010 almost a decade after the trial, had found:
In total, 64 (13.0%) tafenoquine subjects and 23 (14.2%) mefloquine subjects reported neuropsychiatric adverse events, the most common being vertigo, dizziness and various sleep disorders.
On February 10, 2014, Colonel Smith emailed retired U.S. Navy Commander Bill Manofsky, seeking his advice on how best to approach the continued development of tafenoquine “in a much more open, transparent and thorough way than was done during mefloquine’s development.”
In the same email, Colonel Smith wrote:
Weve also had a number of recent interactions with mutual colleagues in the Special Operations community, including with Colonel [Jennifer] Caci as we product developers continually attempt to support their medical and materiel needs.
Several months earlier, in September 2013, Colonel Caci – a senior medical officer at U.S. Army Special Operations Command (USASOC) – had drafted the order banning mefloquine from use in that command and establishing dedicated follow up care for those affected by the drug’s neurotoxic effects. This followed the FDA’s 2013 “black box” warning, which stated mefloquine can cause “lasting or permanent” neurological damage.
Three days before Colonel Smith’s email to Commander Manofsky, Dr Geoff Dow had also emailed Commander Manofsky and Colonel Caci regarding concerns over the drug’s safety. In his email of February 7, 2014, Dr Dow wrote in part:
None of us engaged on tafenoquine wish to repeat the mistakes of the past or to move a drug forward that harms soldiers.
As CEO of 60 Degrees Pharmaceuticals (60P), a company he established in 2010 after having worked as a U.S. Army employee at WRAIR, in 2014 he was engaged by USAMMDA as a contractor for the development of tafenoquine. According to information removed from the company’s website in 2018, 60P has received more than $18 million from the U.S. Army for the continued development of this drug.
These funds included payments for the work undertaken by Dr Dow as part of the 2014 Cooperative Research and Development Agreement (CRADA) between 60P and USAMMDA, which awarded 60P an exclusive license for the drug on the proviso that the company work with USAMMDA to have the drug approved by the FDA and the Australian Therapeutic Goods Administration (TGA).
For additional background, having obtained this license and funding from the U.S. Army, in 2015 Dr Dow stated in an interview with CEO-CFO Magazine that his motivation in seeking tafenoquine’s registration with the FDA was to obtain a “priority review voucher” valued at up to $350 million dollars:
Those vouchers can be sold to another company that allows fast track review at the FDA of an unrelated therapeutic. They are freely salable on the open market. The most recent sale was for three hundred and fifty million by United Therapeutics to Abbvie. Three out of four of our products are eligible for the PRV and it is a financial incentive independent of your actual development program or the therapeutic you are moving forward. Therefore, that definitely has interest for individual investors, but also big pharma who have an interest in molecules that happen to be in your portfolio.
Going back to his email of February 7, 2014, Dr Dow explained that he and Colonel Smith had previously worked together on quinoline drug development at WRAIR. During the mid 2000s, Dr Dow had in fact conducted some of the key studies on which proved that mefloquine is neurotoxic. Dow’s email went on to state to Commander Manofsky that Colonel Smith and Colonel Caci “will be reaching out to you” to discuss “the patient safety and product development risks associated with” tafenoquine. Mentioning the results of the 2009 WRAIR study which found tafenoquine to be “the only antimalarial drug more neurotoxic than mefloquine”, Dow continued:
Scientifically, it would be a mistake to over-interpret [the WRAIR results] and to rush to judgement on a solution that may not achieve the solution we are all trying to seek.
With up to $350 million at stake for Dr Dow’s investors, what’s debatable is whether the “solution” he was trying to seek was, or is, indeed the same “solution” in the interests of those whose health might be placed at risk by this dangerous drug, when safer alternatives were, and are, already available on the market.
During the months that followed those two February 2014 emails from Dr Dow and Colonel Smith, what we can also reveal is that Commander Manofsky and Colonel Caci had arranged for a follow-up study on the Australian tafenoquine subjects to be undertaken by U.S. Navy Captain (Dr) Michael Hoffer, a specialist vestibular physician. The proposed study was to examine any long term damage to the vestibular system among the 1,540 subjects, including the 492 tafenoquine subjects of Study 033, which later provided the basis for Dr Dow’s application to the FDA via this 2017 “integrated safety analysis.”
On August 15, Commander Manofsky wrote:
Just wanting to see if you connected with Dr Hoffer at Balboa regarding possible vestibular analysis of the tafenoquine test subjects in East Timor.
Three days later, the reply from Colonel Smith was, “We obviously won’t be getting anything off the ground,” based on the pretext Captain Hoffer was on leave.
Over the coming weeks, we will continue to reveal and analyse key documents from the Tafenoquine Dossier such as these, including the 2014 60P-USAMMDA CRADA. We will also reveal similar parallel efforts by Australian tafenoquine veterans being stonewalled by their government officials after repeatedly requesting similar follow up studies. What is becoming clear is that these efforts were repeatedly thwarted, with up to $350 million at stake for the pharmaceutical industry and their cronies in key government appointments, as they facilitated the approval of a dangerous drug by the FDA and the TGA.
Editors note: We have approached the current USAMMDA commander, Colonel Gina G. Adam, for comment on the emails and welcome any future response.