Thursday, March 27, 2014

As Ebola Spreads Fear in Western Africa, Pressure Mounts to Deploy RNAi Antiviral

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.

27 comments:

bio said...

These outbreaks are somewhat frequent (annual), this drug has been in the pipeline for 5 years and we have not yet seen use outside of a clinic. It seems less likely that it would be used. However, you're correct in arguing that the case has progressed in both science and transfer in the field. Maybe it could be of use and governments would test it. The flip side, is that it is not FDA validated, so if something goes wrong the potential outcry from African governments as African people are used once again as Guinea pigs for Western medicine would be immense... And if it's only available for healthcare workers that would be equally negative the other direction and favoritism and withholding would come into play. Who knows where it goes and who uses it, but if there is a sizable outbreak, it should be considered.

Anonymous said...

I don't get it! This blog has turned to the bad, dark side...
On the back of these poor Ebola and Marburg patients, your pushing Tekmira. Ethical that is not right. Fornutately the Ebola and Marburg market are tiny tiny. Impact on pps Tekmira is $0.112.
Tekmira and HBV too. Nothing has left the dark of the Tekmira house yet, but you talk like the chief science of Tekmira. You are the dark side of good blogging. Best you put the DISCLAIMER on the top of your HP, not at the bottom!

Anonymous said...

Maybe you were a good scientist, but thats long way since ...
Why are you not working in the RNAi field? Sector is hot, no job there?
You are making living with stocks not with RNAi science.

BIAS BIAS BIAS!

tufulipo said...

While I find the premise of emergency deployment of the TKM Ebola therapy an interesting question, I see no evidence of "pressure" mounting to use it in the recent outbreak (save from TKM investors on message boards).
Perhaps you could cite such evidence to elevate the blog entry above the level of "fomenting", as Cramer would call it.

-bio said...

Really guys? You hit Dirk for not being 100% spot on and you spout this crap? 11.2 cents per share valuation for Ebola/Marburg?

It's a far more solid program than 11.2 cents. The question is when it will be available and how much stockpiling will be involved. Dirk's assessment of timing 2016/2017 and valuation is quite reasonable.

I think everyone needs to get back to reasonable evaluation, emotional tempering on all sides, and rational discussion. But then again, people are only interested making all the profit in 3 days...

While summer is often boring for biotech, I believe everyone in the space will benefit from ARWR pIIa data and get a very solid push. TKM will benefit from the HepB derisking. More than 11.2 cents too...



Richard Lund said...

I support the use of these drugs to help the people who are sick. (seems so obvious, but I guess I grew up in another era or place) This will not be the first time an interest in profits will be involved in medicine.
If the CEO of $TKMR believes that they have a viable drug, let him offer the help. If the governments involved say no, that is their responsibility.
Why not turn a Golden opportunity into a Golden Rule opportunity?

Anonymous said...

Here's some evidence the problem isnt contained...

http://www.reuters.com/article/2014/03/28/guinea-ebola-idUSL5N0MP2UB20140328

if there is a potential cure and there may be foreign physicians there assisting why wouldn't they want want it available to them? Its moronic to say Dirks out to lunch on this topic..

How about we send you there without the antidote and see if that makes sense..

Anonymous said...

The character of a man is invariably revealed when his money is at stake.

I am beyond disgusted to see the depth Dirk Haussecker will stoop, to pump up his investment in TKMR.

The tweets and blog desperately try to sensationalize Ebola, latest equating it to Avian Flu as TKMR pps continues to deflate from his hot air.

Flu affects millions, Ebola hundreds, if that, some years, NIL.

Reading the tweets and re-tweets reveal the misguided hope that TKMR stock will double overnight if panic and fear could be incited.

One can not avoid this eerie feeling that if he could get the virus to spread he would do it to profit.

I have amused myself parodying Dirk Haussecker and his blog else where, but there is nothing to be funny about anymore.

This man is dangerously missing the sense of right and wrong.

- investron

Anonymous said...

Investron, are you kidding me? If I had a product/skill that could save lives and make money, you bet I would be touting it all over the place and given any opportunity extolling it. Thats a good thing. Save lives and make money. Whats wrond with that?

Actually thats what I do, I am an oncologist. Should I not market to my referring doctors of my expertise?

Please spare us your bs philosophical "character of a man", nonsense.

You are the guy in arwr right? dude just buy both and get over it. Even dirk is holding arwr Im sure for the upcoming news in it.

Oncdoc

Anonymous said...

Investron, are you kidding me? If I had a product/skill that could save lives and make money, you bet I would be touting it all over the place and given any opportunity extolling it. Thats a good thing. Save lives and make money. Whats wrong with that? Dont doctors do that? Go after them to for marketing.


Please spare us your bs philosophical "character of a man", nonsense.

You are the guy in arwr right? dude just buy both and get over it. Even dirk is holding arwr? maybe ? for the upcoming news in it.

Latebloomer said...

Dirk knows that I'm very critical of his two recent posts on ARWR, and he's allowed me my say in the comments of those posts. And, in fact, while I was just recently invested in both ARWR and TKMR, this past week I consolidated my RNAi investment behind ARWR because I think what's coming this summer is so important for the company.

But as far as what's happening with Ebola at this time, and with what Tekmira can potentially do about it via their RNAi solution, which has come so far after a lot of work over several years, I'm all for it being deployed under some sort of "compassionate use" application. It's now even had at least some amount of time testing for safety in healthy humans, which may be as far as anything promising for Ebola has gotten to date.

And if Tekmira the company and its investors benefit from that deployment, I don't think that ultimately hurts me as an ARWR investor. It may even benefit me due to the attention it may bring to RNAi, giving further important proof of concept to it, not so unlike ARWR's report this summer regarding its initial clinical results for HBV will likely also be beneficial to Tekmira investors and others in the RNAi space, and especially others going after s-antigen KD. But if Tekmira's treatment for Ebola is deployed to help in this outbreak, and it does somehow hurt me in my investment with ARWR? Well, so be it.

Heck, a lot of us, involved in one or both companies, have been happily discussing the marketing potential for something that could have a very important new impact on HBV, while in the same moment, also being excited about what it could do for patients. I don't see this as any different.

I think Tekmira and its treatment for Ebola could make a tremendous difference to those suffering from this awful outbreak, including the fear that this is generating. And the longer the delay in getting the go- ahead, if it is to come, then the longer it will be before the manufacturing gets started and the treatment deployed.

I'm very interested in this story (for all sorts of reasons, some of them selfish, some of them not) and want to be kept abreast of it.

Linda

Anonymous said...

No one should take Investron seriously. He is the ARWR propagandist in chief over at the Yahoo message. Truth and fact come under equal assault in furtherance of his pro-ARWR agenda. And I am an ARWR shareholder.

Investron's only problem with Dirk is that Dirk is not furiously pumping ARWR.

-bio said...

http://www.voanews.com/content/development-of-antibodies-rushed-to-treat-ebola-outbreak-in-guinea/1880886.html

Looks like Monoclonal antibodies are already in Guinea to help the people there. Interesting to see how this develops.

Dirk Haussecker said...

-bio: If they send antibodies, they send TKM-Ebola (the most advanced and validated) there, too. This would explain why there seems to be apparent stoppage of the phase I TKM-Ebola trial as the trial recruitment link on the ICON website has disappeared.

The trial would probably be stopped as the limited phase I supplies of TKM-EBOLA would dictate that they'd be better spent on actually infected persons instead on healthy volunteers.

Also odd is that according to the old ICON link they added a 5th cohort to the single-ascending dose part. Only 4 had been planned. I initially thought that maybe due to a good safety profile they wanted to test an even higher dose than the top dose originally planned...In retrospect, has this been an emergency cohort they wanted tested before sending over the supplies to Guinea.

Tufulipo...if you have the most advanced treatment for Ebola and people in Guinea are dying in what may be the biggest outbreak in a decade or in recorded history...that's no pressure to send? Please...

Anonymous said...

Guys, whether or not TKMR is actually at this time sending EBOLA therapy over, must say, Im proud to be in a company that if not today, will, very soon (God willing), have treatments that will save lives. Finally we have companies targeting diseases such as Hep B and Ebola that are much much more prevalent in third world companies regardless of immediate lack of financial gains. Seems like this trend that ARWR started is catching on. Establish your platform and then go for the bread and butter USA stuff. ie, solid tumors, hyperlipidemia, Diabetes Mellitis etc. Ie, Bat wings for now and Hot dogs later.

Oncdoc

Anonymous said...

Dirk, you should branch out to related areas such as immunotherapy vaccines and adult stem cell drugs. Companies like TapImmune and privately held Regen Biopharma look very promising. RNAi is not the only new drug class emerging.

tufulipo said...

Dirk, I totally would like to see the TKM Ebola therapy get tested and succeed in the field. I simply am not convinced that the powers that be are prepared to bend their protocols to allow it. The announced spread to Liberia does increase that possibility, I agree. But in a game that appears to be, to date, all speculation from afar, somebody needs to play the skeptic. The chance that the world will align the self interest of western investors with the salvation of sick Africans is always a long shot.

Dirk Haussecker said...

'The chance that the world will align the self interest of western investors with the salvation of sick Africans is always a long shot.'

The premise for most skeptics appears to be that since it could/would benefit investors, it won't happen. My premise is that the authorities deciding which steps to take don't weigh that too heavily, if at all. Aren't you in RNAi Therapeutics to do well while doing good?

tufulipo said...

>>Aren't you in RNAi Therapeutics to do well while doing good?>>
Is it your experience that "good" and "profitable" often wind up standing together under the same goalpost? In Africa especially, the historical opposition of these two is rather blatant. 'What I wish for' has no standing in these proceedings.

Anonymous said...

Don't wish to belittle the plight of Ebola victims but where is RNAi at re Alzheimers? This carries a massive liability in western economies. Way more than HIV, HBV, HCV or anything else.
None of the leaders have declared a program for it despite it being a gene based disease.
Must be the one being developed in secrecy and this TKMR v ARWR debate is the straw man debate.

tufulipo said...

Hope you're not misinterpreting me as an armchair ethicist, opposed to making profits. My point is simply that laying out only positive interpretations from a muddle of data in Africa is misleading.
eg...
> TKM Ebola Rx the reason 8 cases in Conakry have only resulted in minimal deaths so far
>shipping product to Africa is the explanation for the sudden disappearance of a cohort (on a website) in the safety trial
>another company's announcement it is shipping unapproved product to Africa is evidence TKM is also shipping

It doesn't take much sophistication of imagination to name a host of other explanations for these phenomenon. Not all so rosy.

We would all like to see TKM Ebola mop up that contagion. Betting it will even get the chance is another thing altogether.

Dirk Haussecker said...

Tufulipo...as you know, I love to speculate. In fact, speculation and the ability to think of things never seen before is what is pushing science forward and make investors successful. This is a small world. If there is an Ebola outbreak anywhere in the world, Tekmira will be part of the response in one way or another. In fact, Tekmira not being consulted in the current outbreak is far more unlikely than speculating that they are.

TKM-EBOLA is probably the drug candidate in which most has been invested and you believe it is not being seriously considered?

Anonymous said...

The problem is getting worse.. health care professional are fleeing hospitals when patients are being admitted.. http://www.malijet.com/actualite_internationale/97683-guin%C3%A9e-dinguiraye-les-m%C3%A9decins-fuient-l%E2%80%99h%C3%B4pital-%C3%A0-cause-d%E2%80%99un-mal.html

Anonymous said...

Dirk Haussecker, you should be ashamed of yourself! Using the politics of Africa and the plight of their peoples for your self promotion. Just another spectacular endorsement of your ethics or lack thereof.

Terry Chrisomalis said...

Tekmira is a good company with a good delivery technology, but investors should check out RXII (Rxi Pharmaceuticals) has combined RNAi together with antisense technologies best of both worlds and combined it into a drug compound with no delivery vehicle at all. You can learn more about Tekmira and Rxi Pharmaceuticals at my website http://www.biotechpicklist.com/

Anonymous said...

What surprises can we expect from the AACR conference over the next few days re RNAi efficacy?
Lets hope this is where the straw men with their straw man arguments end the charade and put up something of real meaning other than the dissection of a price movement in any one company.

Anonymous said...

Dirk, am dieing to know (but not of any viral borne disease) why it is, when I look through all those years of posts you have made, barely any of them confront the biggest scourges of civilized western society. They being AD and cancer.

Are you missing something in covering this field? Or are we seeing a price?

The price of selling scientific and personal integrity.

Still long MRNA?

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