A day or so following reassurances by the Guinean authorities that
the Ebola virus outbreak had been contained and was under control, news
is making the rounds of confirmed lethal cases in Conakry, the 2 million capital
city of the country, and in neighboring countries in Western Africa. With the death toll rising, the disease
spreading internationally, and the virus paralyzing affected areas, pressure is mounting to
call in an RNAi Therapeutic which has proven to be effective in the most
stringent efficacy models possible. 66
are thought to have died from the disease by now, at least 4 of which are healthcare workers.
The therapeutic, developed by Tekmira Pharmaceuticals and
funded by a $140M contract from the US Department of Defense, has shown 100% post-exposure
survival in monkeys infected with the otherwise highly (90%) lethal Zaire
strain of the virus. This is the same
virus ravaging through Western Africa right now. Because of this, the Ebola therapeutic which
targets two viral sequences simultaneously and which entered phase I in-man
studies earlier this year, there is a very high likelihood that TKM-Ebola will
be applicable in this situation.
Only days ago, TKM-Ebola was bestowed fast-track status by the FDA.
Under normal circumstances, licensure of TKM-Ebola would
follow the Animal Rule. According to the
Animal Rule, treatments for diseases for which it is either impractical or
unethical to conduct efficacy studies, can be approved by the US FDA if
sufficient efficacy can be demonstrated in stringent animal models (monkeys
here) and human safety at corresponding dose levels. Ebola obviously is a candidate for the Animal
Rule since experimental infections of humans cannot be done ethically and
natural outbreaks are so rare and unpredictable.
Following the demonstrations of animal efficacy, the
ongoing single- and multi-dose ascending phase I in-man study for which the
single-dose phase appears to have already concluded is designed to confirm such
safety. To make sure that the findings
are robust, this is typically followed by larger animal efficacy and human
safety studies. At this point (~2016/7),
the FDA would make its decision regarding licensure which would lead to stockpiling
orders from the US government for preparedness against bioterrorist attacks.
Arguments for deployment of TKM-Ebola in Western Africa
Although TKM-Ebola has not completed the formal requirements
under the Animal Rule, it is fair to assume that TKM-Ebola, the most advanced Ebola
anti-viral in development, will do more good than harm in a disease without alternatives besides supportive care. With a lethality of 80-90%, I would certainly
take my chances.
A deployment would serve at least two purposes. Firstly, it would give us a chance to confirm
the effectiveness of the RNAi Therapeutic in actual humans. In addition to the scientific value, if I were the US government, I would be eager to take advantage of the unique
opportunity at testing efficacy before spending billions on an agent for which there is only
theoretical human efficacy.
Secondly, having TKM-Ebola as a standby in hospitals would
help restore some calm and confidence, especially among the healthcare workers which
need to contain the outbreak. It is also
most likely that from a logistics point-of-view, this is the population where
TKM-Ebola would be most effective as it is here where the disease can be
detected and drug administered early enough for the treatment to be effective (within 2 to 3 days
following exposure).
In order for TKM-Ebola to have maximal impact,
manufacturing would have to be scaled up (I estimate ~2 months for the
production of large lots) and the logistics around diagnostics and treatment
administration put in place. Nobody
knows whether the current outbreak will spread further, but it is better
to be prepared in case it does. As the suspected Canadian case this week illustrated, Ebola is now just a plane ride away from
us.
Watch out for the
April 1 presentation by Dr. Ian MacLachlan from Tekmira on the latest data for
TKM-Ebola which will be in front of a sell-out crowd at the FILO 2014
conference in Galveston, Texas.
