There could not have been a worse timing for the
Clinical Halt imposed on Tekmira’s RNAi candidate for the treatment of Ebola viral
infection, TKM-EBOLA. Just as the disease is
reaching epidemic proportions in Western Africa (>500 dead), the world’s
leading drug candidate for this infection with validation in the most stringent monkey models got
stopped in its tracks following concerns by the US FDA regarding its
immunostimulatory potential that was evidenced in the single-ascending dose
part of the study (discussed
here).
Efficacy in monkeys is the best you can hope for in the
absence of an actual outbreak such as the current one,
so I was hopeful that
TKM-EBOLA could become part of the solution, especially by providing an
incentive for patients to identify themselves and come to the treatment
centers. It is the prospect of dying
surrounded by people in space suits instead of loved ones, and even worse the
prospect of being infected by Ebola in the first place from fellow ‘inmates’ if
you have been misdiagnosed that keeps people away from the hospitals. This appears to have been key to the continued spread in addition to cultural practices such as kissing the dead as the WHO likes to emphasize (in my opinion, the condescending attitude by the behind-the-curve, out-of-touch
WHO has been the 3rd key factor).
I suggest to mobilize
the financial resources to fly in the latest medical equipment and offer
patients to be treated with something that might help them survive.
Instead, immune-related side effects such as flu-like
symptoms in healthy volunteers made the FDA ask Tekmira to provide additional
data and explanations to justify proceeding to the multi-dose ascending part of
the study conducted under the Animal Rule regulatory pathway.
In a way, this development might be considered support for
those that have said that it is too early to treat
patients with TKM-EBOLA, or any other experimental treatment for that matter. On the other hand, you could
also argue that this only shows that it is unethical to test it in human
volunteers where the tolerance for side effects is much less than in somebody with a ~70% risk of dying from an infection otherwise.
Just look at the cancer drug development field, and at least in RNAi
Therapeutics, I have never seen them tested in healthy volunteers even in phase
I, but straight in cancer patients that have little to lose.
In fact, the immune stimulation could be the price to pay
for a cure as it might be part of the mechanism of action of TKM-EBOLA either
by shutting down viral protein translation and/or by interfering with the
virally-induced cytokine storm itself.
These scientific issues, also as it relates to Tekmira’s platform in
general, will be discussed in a follow-up post.
Test of Tekmira's credibility
I would like to close with some remarks on the credibility
of Tekmira’s management.
Management did
in fact
disclose the risk that there might be delays with the phase I study following
results from the single-dose part of the study when it said there would be FDA review ahead of the multi-dose part of the study: '
Interim safety data submitted to the FDA for review May 7, 2014.'
Although this could be read as part of the
normal regulatory process, the fact that they disclosed it made me believe that
this was a real possibility. The
positive spin on the data obviously falls under the Safe Harbor of ‘
forward-looking statements’ and no foul play here.
In fact, many biotechs would not even have disclosed the FDA review.
On the other hand, many investors went along with the positive
sentiments by management and will feel disappointed now. In order to redeem themselves to this
constituency, management will now have to prove that they were already prepared
for this event and that they can speedily answer the questions and provide the
requested data so that the trial may resume asap and that TKM-EBOLA may be
offered to those in Western Africa now that it can be considered that the drug
has been fully vetted for safety.
6 comments:
As always much appreciated that you continue to educate.. keep up the great work dirk.
A little while ago the CEO of BLT made a presentation to AZ selling their wares. In it, it was stated their ddRNAi technology was being used by Tekmira along with several others.
Now TKMR's Ebola program gets halted.
Not a good look for TKMR. Or BLT. Or any of the other companies named in the AZ presentation. And kind of rings the death knell for ddRNAi as a platform technology.
Wouldn't be surprised if the Calimmune trial meets the dame fate. Or the BLT HCV trial.
Which makes the recent TV appearance of the BLT CEO and his claims all the more bewildering.
Where does that leave ssRNAi? Maybe it really is "da bomb"
Dirk, I know you've spoken highly of ssRNAi previously, and of ISIS. Now you're saying TKMR is a no go except if you're long.
Does that mean ISIS is a buy in your opinion? Or ALNY because they're about to deal with ISIS and you're on their payroll.
Don't be so quick to write off BLT. They're in trials now and will be able to put Dirk's "no lab" issues to bed once n for all very soon.
I think previous poster is wrong about ISIS developing ssRNAi. That's what RGLS was set up for.
Wouldn't be surprised if BLT buys them out same way they did Tacere.lol
Is RGLS the proprietary holder of ssRNAI? Sounds like that's what previous poster is saying.
Dirk, I'm sure you've said ssRNAi is proprietary to RGLS. Is this true?
If anyone will know it will be you.
Pardon me, but wasn't the study done in healthy patients? Therefore, there was no "virally induced" cytokine storm, but is due to the presence ofxenobiotic material. Then again, whether cytokine stimulation will have any good/bad effects remain to be seen. This was discussed in the 2010 article. And isn't the MOA of rnai fairly well understood? Does the immune system play a role? In rnai therapy? How much?
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