seekingalpha.com: Genzyme and Isis Announce FDA Approval of KYNAMRO™ (mipomersen sodium) Injection for the Treatment of Homozygous Familial Hypercholesterolemia

[PeterMP]

"The market is small? We know that. Yet we did not miss the fact that January 30, 2013, the day Kynamro's was granted approval, will be recorded in the textbooks of pharmaceutical sciences as the day the first systemically administered antisense therapeutic has been approved by the FDA"


http://seekingalpha.com/article/1150...re-for-company
This is potentailly a big deal not because of this particular drug, which has serious side affects and is treating something very rare.

But because it is the first approved drug based on RNAi, which can potentially be used to treat all sorts of things, from genetic disorder, alzheimers, and HIV infection.

http://www.ncbi.nlm.nih.gov/pubmed/21537948
http://www.ncbi.nlm.nih.gov/pubmed/22709537

Potentially, anything where we can say this gene is involved and lowering the amount of its product would help, you could treat.

[Burgold]

That was a tough read. Is it me or was it written in a very vague way especially for something designed to catch an investors eye. I'm not sure what the market is or why this was a particularly unique invention or process.

Mind you, it could be one of those where my social sciences background versus chemistry background is handicapping me, but I wound't mind learning more why this one really caught your eye.

Mind you, the antisense aspect, that the strand could counter program certain genes or at least stop it from continuing a function is interesting.

[China]

I agree with your assessment of the significance and potential importance of RNAi therapeutics.

I also agree with Burgold that the thread title comes across as an ad for Genzyme and Isis, and the official press release is really geared towards investors.

[Corcaigh]

I know the mods like detailed descriptive thread titles, but this may take the cake.

[PeterMP]

I agree with your assessment of the significance and potential importance of RNAi therapeutics.

I also agree with Burgold that the thread title comes across as an ad for Genzyme and Isis, and the official press release is really geared towards investors.

I couldn't find a more general article that discussed it in terms of the real potential long term impact very well. Most are either like this or assume you have foundation to understand RNAi and understand therefore this one is novel.

I thought it was good enough that this clearly stated this is a first.

---------- Post added February-24th-2013 at 02:55 PM ----------

Mind you, it could be one of those where my social sciences background versus chemistry background is handicapping me, but I wound't mind learning more why this one really caught your eye.

The big thing is it is the first. For about decade or so now people have been sayhing we should be able to use these technique/process to treat disease/infection, but this is the first using this process/technique.

This MIGHT end up making antibiotics and vaccines seem unimportant in comparision. Even they were limited to infections. This potentially could be used to treat infections (including viruses for which vaccinations have yet to be produced for or been affective against) and non-infectious diseases.

For several years now I've been teaching this topic and saying this MIGHT happen. Now, it has. In 20 years, it is possible that I will have a group of students and for essentially any viral infection for most of their lives (most of their memory) is going to the doctor and getting an antisense (RNAi) treatment, and I'll be telling them about BEFORE that was possible.

Kind of like now I teach about how things were before we could sequence genomes.

[Warpath11]

Very cool indeed. Though not sure about the ROI on this one for Sanofi/ISIS the patient base is so small and I'm sure the injection will be crazy expensive that you'll have a hard time convincing payers covering any of the cost. Seems like once a week is a bit much they need to figure out how to make the antisense stick around longer...AAV in people anyone LOL not quite ready for that. Not to mention the long term inhibition of ApoB synthesis will more than likely lead to steatosis (fatty liver).

[AsburySkinsFan]

I have no idea what any of this means.

[LD0506]

I have no idea what any of this means.

Glad I'm not the only one, thanks

Είναι όλα τα ελληνικά σε μένα

[PeterMP]

I have no idea what any of this means.

RNAi is a process that your body does naturally as a defense against certain viruses. It was only really understood/discovered in the late 1990s (people working on it in the 1990s were given a Nobel Prize in 2006) and even then in lower organisms and plants.

Using this already biological process, we can trigger the biological system to do certain things by introducing foreign molecules. The big thing is that the RNAi process is general and yet specific. I can specifically trigger a certain response by using a specific molecule using the RNAi system. Through RNAi I can use a slightly different molecule and trigger a different response.

The molecules that I am using to trigger the response are slightly different and that difference gives me specificity, but they are also very related and the same general processes can be used to make them both and they are both acting through the same general process (i.e. the RNAi process).

Right now, most drugs are pretty specific in terms of their structure (and therefore how they are made), and their function (what they interact with on the biological level), which means they have specific ways to make them and in order to treat the disease I have to find something specific that will interact with the system causing the disease.

People have been using RNAi for quite a while to study the biological system (e.g. if using RNAi I cause the organism to do X (where X is happening at the molecular level), what is the broader impact on the organismal level).

This is the first drug approved that works by triggering the RNAi system to cause a biological impact in humans.

I'm not sure if that explanation will help or hurt.

The key is it is easy to imagine that a lot of other diseases will be treated using this same general approach/technology, and this is the first.

(It is easy to imagine that it will, but there it might not. There are some real hurdles still too over come.)

---------- Post added February-25th-2013 at 09:46 AM ----------

Very cool indeed. Though not sure about the ROI on this one for Sanofi/ISIS the patient base is so small and I'm sure the injection will be crazy expensive that you'll have a hard time convincing payers covering any of the cost. Seems like once a week is a bit much they need to figure out how to make the antisense stick around longer...AAV in people anyone LOL not quite ready for that. Not to mention the long term inhibition of ApoB synthesis will more than likely lead to steatosis (fatty liver).

I know in other cases there is some work with intranasal introduction of the antisense molecules in mice that looks promising. I don't know if there are drugs going through clinical trials based on the same idea. I think it also might depend on what tissue you are trying to affect. It seems to me that affecting the liver intranasally might be hard.

[Warpath11]

I know in other cases there is some work with intranasal introduction of the antisense molecules in mice that looks promising. I don't know if there are drugs going through clinical trials based on the same idea. I think it also might depend on what tissue you are trying to affect. It seems to me that affecting the liver intranasally might be hard.

Yeah targeting that therapeutic to the liver after inhalation seems like a long-shot at this point. The best way to get it to the liver, long term is to use AAV, though even that is well beyond of what you can do to humans. AAVs have shown lasting effects in pre-clinical models upto an including non-human primates. So there is promise there but obviously still far off.

[PeterMP]

Yeah targeting that therapeutic to the liver after inhalation seems like a long-shot at this point. The best way to get it to the liver, long term is to use AAV, though even that is well beyond of what you can do to humans. AAVs have shown lasting effects in pre-clinical models upto an including non-human primates. So there is promise there but obviously still far off.

I think there are even some AAV (adeno-associated virus for anybody that is curious (I had to look up the abbreviation myslef)) going through the FDA process in humans, but I think that is mostly classical gene therapy stuff.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829748/

I don't know of a case where the AAV is being combined with RNAi in humans, and I'm not sure how long lasting it is (doesn't depend on the cells replication rate).

Personally, I would be worried that there is an RNAi based on induction of gene silencing in humans or long term the RNAi is going to cause some other affect (unless there is a method to turn the AAV off or "pop it out" of the cells).

[Warpath11]

I think there are even some AAV (adeno-associated virus for anybody that is curious (I had to look up the abbreviation myslef)) going through the FDA process in humans, but I think that is mostly classical gene therapy stuff.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829748/

I don't know of a case where the AAV is being combined with RNAi in humans.

Personally, I would be worried that there is an RNAi based on induction of gene silencing in humans or long term the RNAi is going to cause some other affect (unless there is a method to turn the AAV off or "pop it out").

Yeah you are correct most of the work around AAVs is used to 'over-express' a target gene but in the future there are talks of it potentially delivering RNAi (obviously in a more controlled manner), like I said earlier, it is way far off in the future but the use of AAV to over-express proteins, particularly in the liver, pre-clinically, has been used for many years now with very good success.

[Prosperity]

Cool, btw is RNAi the only way the body defends against viruses?

[PeterMP]

Cool, btw is RNAi the only way the body defends against viruses?

No, you can trigger a classical immune response to viruses, which is why vaccines work.

[AsburySkinsFan]

RNAi is a process that your body does naturally as a defense against certain viruses. It was only really understood/discovered in the late 1990s (people working on it in the 1990s were given a Nobel Prize in 2006) and even then in lower organisms and plants.

...long story short...

Ok, I semi understand that what they are doing is introducing a molecule (into what?) which then triggers a specific response from the body's (immune system??) in order to defend against disease.
How is this different than a vaccine? I know that vaccines use a germ (or replica) that tricks the body into producing defenses against the live/real version so when the live/real version is encountered the body already has a defense ready for it.