Biovista and CAA identify candidate drug for repurposing

[alex3619]

As I said before Firestormm, there is a move amongst big pharma to reformulate drugs .. new doses, combos etc. Though the drugs are old, this qualifies for a new patent, and hence new profits. That appears to be what they are doing here. It also enables them to put a premium price on the "new" drug.

 

[WillowJ]

At first this sounded like a (relatively quick?) repurposing, which was really exciting. Now i see that it will probably be a bit harder. IND sounds like it would take several years, and patenting sounds like it would create a brand-name drug which might put it out of reach to some. I guess the formularies would have to list it as a "preferred" brand since there are no treatments on file for this diagnosis, but that is still more expensive, sometimes $70 for a 30-day supply or 50% of cost.

All the same, it's great to have something in the pipeline! We have been looking for this for a long time.

 

[Firestormm]

As I said before Firestormm, there is a move amongst big pharma to reformulate drugs .. new doses, combos etc. Though the drugs are old, this qualifies for a new patent, and hence new profits. That appears to be what they are doing here. It also enables them to put a premium price on the "new" drug.

At first this sounded like a (relatively quick?) repurposing, which was really exciting. Now i see that it will probably be a bit harder. IND sounds like it would take several years, and patenting sounds like it would create a brand-name drug which might put it out of reach to some. I guess the formularies would have to list it as a "preferred" brand since there are no treatments on file for this diagnosis, but that is still more expensive, sometimes $70 for a 30-day supply or 50% of cost.

All the same, it's great to have something in the pipeline! We have been looking for this for a long time.

OK. So I am here busy trying to translate the translation of Day Two Video 3 from the FDA thingy in April. This question posed by Vernon and answered by Munos appeared most appropriate in answer to your question, Willow, about timelines:

Suzanne Vernon: I have a question for Bernard. I think that you alluded in your presentation to the fact that CFS appears to be on the right track as far as being able to be innovative and expedited in a disruptive way [*]. What kind of time frame would you put on us being a Chordoma or an MMRF or one of those organizations that clearly is innovative and doing good things?

Bernard Munos: I can give you a couple of rough sums [estimates?] there. If you go and try to develop a drug the traditional way, you are talking about a 10 to 15-year timeline, which is probably more than the patients in this room would like to see.

If you go the drug repurposing route the hope is there is that you can bring innovation to a patient within five years.

This can be speeded up if patients do join hands and collaborate and work together to help make it happen.

You've got physicians, scientists out there waiting to help literally; they just don't have the tools and they don’t have the data. I was thinking last night, that in any disease, natural studying involving a thousand patients would be a godsend, would be something that is hard to fathom [imagine], but, needless to say enormously helpful to scientists.

The technology is available today and would probably allow thousands of CFS patients to enroll and collect the data within the next few months and make it available to the scientists. So I really think whatever timeline I can talk about, it's too long, but they can be shortened dramatically by getting serious about it and I know you're serious about it but I think you need to connect maybe better than you are right now.

Go to patients like me [and compare them to] those in the CFS community: there are hundreds of people like me and I think we have a million people with CFS in this country. There are many that could contribute but are not contributing for various reasons although, perhaps, simply because they are not aware of the possibilities. That's what we need to get better at. But I think if we do, we'll see those timelines shrink.

[Firestormm says: I didn't understand her use of 'disruptive' here. Any help would be appreciated. Thanks ]

 

[Nielk]

From my understanding of listening to the FDA presentation by Vernon, it seems that these two drugs are existing drugs which are being considered being used in combination.
It doesn't seem like they are reinventing the wheel here. They just took ALL the data that is out there, online and from physicians who are currently treating ME/CFS patients. They then came up with two drugs that have shown the greatest success in symptom management. They now want to try these drugs in combination as an effective treatment for ME/CFS.

By the way, I am really confused as to how they arrive at the estimate of one million patients in the US? Where are they? It is obvious that most of them are hiding and if they are, how do we know that they exist?

 

[alex3619]

The estimate of US patients at one million is the lower end, with the higher (and mure dubious) at 4 million. However its also estimated that a high percentage are undiagnosed. This is from various surveillance data, and I don't know how accurate it is. Personally I think the prevalence is between 0.2% and 0.4%, but that data is really old now, and if there is a growth curve it could be much higher and have been missed. We really need a diagnostic biomarker then a decent prevalence study.

Don't forget a percentage, and possibly a high percentage, of CFS patients will be misdiagnosed, and many will later lose the diagnosis accordingly.

Fukuda criteria data is not likely to be that accurate either.

These are all guesses, unfortunately, as I don't think any of the surveillance data is that reliable.

 

[jspotila]

Thanks Jenny I still don't understand however. When Vernon made her presentation she was talking about existing drugs being repositioned. I had assumed from this that there was no 'new drug' (IND). Sure the two drugs concerned might go through a 'rebranding' exercise as their original purpose will presumably change (though perhaps not), but their target audience presumably has changed.

Anyway, their trawling of the existing literature, the databases, and the survey revealed drugs that were seemingly effective at helping to manage one or two symptoms - we could be talking headache and muscle pain or something. So again I can't understand this 'secrecy'.

It's my understanding at fault here. I'm not suggesting any of this is intentional on their part.

Thanks again.

My (imperfect) understanding is that because these two drugs have not been tested in combination before, that makes it an IND. Hence the need for proof of concept and the upfront secrecy until the IND application is approved (for a clinical trial to go forward).

My understanding is also that the hope is that this repurposing can be accomplished in LESS than five years. However, that depends on how the trials go, of course. But the goal is to move through this process in significantly less than five years.

 

[jspotila]

By the way, I am really confused as to how they arrive at the estimate of one million patients in the US? Where are they? It is obvious that most of them are hiding and if they are, how do we know that they exist?

The 1 million number comes from a Lenny Jason study using Fukuda criteria. The 4 million number comes from a CDC study that used the empiric criteria, and that's why many people think that number is too high. But prevalence studies have been all over the place. The recent Vincent prevalence study was less than 1 million.

The other issue is the percentage of those who have been diagnosed. The general sense is that less than 20% of people with CFS have been diagnosed with it. That means we have 200,000 or less diagnosed out of that 1 million number.

I'm not aware of any prevalence studies using the Canadian or ICC. Anyone?

 

[Firestormm]

The 1 million number comes from a Lenny Jason study using Fukuda criteria. The 4 million number comes from a CDC study that used the empiric criteria, and that's why many people think that number is too high. But prevalence studies have been all over the place. The recent Vincent prevalence study was less than 1 million.

The other issue is the percentage of those who have been diagnosed. The general sense is that less than 20% of people with CFS have been diagnosed with it. That means we have 200,000 or less diagnosed out of that 1 million number.

I'm not aware of any prevalence studies using the Canadian or ICC. Anyone?

Exactly the same situation as we have over here across the pond. Pain in the arse - for everybody! At least it's been acknowledged over here now (see other thread about UK MRC Collaborative).

Never the twain shall meet? I couldn't possibly say. Perhaps we'll get there; but trying to base a 'networking' campaign on contacting a million patients is highly unlikely to succeed I would suggest.

One only has to consider the membership of the national ME charities. If we assumed there were some 250,000 affected by ME in the UK (which is a guess at best in my opinion though some estimates are well in excess of even this); membership wouldn't amount to 5% of this I would estimate.

A reasonable goal might be to try and contact - bring on board - say 50% of this combined membership with any BioBank or patient registration campaign perhaps. One has to be realistic. Ambitious, yes, but realistic.

On second thoughts perhaps I'm overly pessimistic. There was a national campaign of a patient registration project - major money - by the MS Society and I think Liverpool University. Serious effort. Lovely, shining, database.

They were chasing me the other day because I hadn't visited their site for over a year! And I don't have MS. People have to be motivated to sign-up to a venture especially one - I would argue - that is being run by an organisation that perhaps they don't directly have any any contact or feel a desire to support.

They need to have the time. And these are after all patients

Sorry. Am rambling. As was once my want

 

[urbantravels]

In answer to the question about "disruptive", it's a reference to "disruptive innovation," and it's meant to be positive. However I'm afraid it's become a bit of a buzzword and is sometimes used too broadly, meaning just "innovation" or "rapid innovation" or "innovation we like." See the Wikipedia article on disruptive innovation:

http://en.wikipedia.org/wiki/Disruptive_innovation

Well, you don't have to wade through the whole article, just the first couple of paragraphs.

 

[WillowJ]

thank you, Firestormm

but what are we supposed to sign up for?

 

[Firestormm]

In answer to the question about "disruptive", it's a reference to "disruptive innovation," and it's meant to be positive. However I'm afraid it's become a bit of a buzzword and is sometimes used too broadly, meaning just "innovation" or "rapid innovation" or "innovation we like." See the Wikipedia article on disruptive innovation:

http://en.wikipedia.org/wiki/Disruptive_innovation

Well, you don't have to wade through the whole article, just the first couple of paragraphs.

Much obliged, urban

 

[Firestormm]

thank you, Firestormm

but what are we supposed to sign up for?

I would imagine it's 'the' or 'a' patient registry, or 'the' or 'a' BioBank, Willow. What would then be a next step would be for the various nation's initiatives to link-up internationally; and make this data far more useful to any poor scientist willing to wade through it all.

We have initiatives in the UK and you have yours with CFIDS in the USA. There are probably others either running or proposed elsewhere. If organisations behind these initiatives could meet on an international footing, and ensure their projects are capable of 'linking-up' internationally; then this would meet one of Dr Munos' other suggestions.

However, I still think that CFIDS have it right. It will be the support organisations that take these initiatives to the next level i.e. by linking up with someone like Bio vista. I don't quite imagine - as Dr Munos implies - any scientist will be willing/able to wade through raw data.

It seems more likely that any data will need processing before it can be taken on by an independent scientist. Also the means of collection needs careful consideration. If it's blood data i.e. biological - well that's one thing, if it's data taken from trawls of the scientific literature or clinician/patient surveys - well that's quite another.

Data is data but it doesn't mean it is always useful and someone has to decide what is and what isn't going to be useful data. Dr Munos was also talking about patients using/wearing 'Fit Bits' that will collect 'exertion' data - which is fine but much thought would need to be given as to how this data is collected and processed.

Someone - CFIDS is the more likely candidate I guess - will need yet another databank to collect data that is so arbitrary and possibly 'random' as might be implied by multiple (possibly hundred's of thousands, even millions) of uploads of personal exertion-data. It might prove useful to some scientist somewhere/sometime - but will require much careful thought beforehand.

 

[Nielk]

The FitBit which Dr. Munos talked about is actually a great tool to amass information. When I took part in the Mt. Sinai study a couple of months ago, I had to wear one the entire 4 days of the study. It tracks all activity like steps, distance, stairs climbed as well as sleep cycles. It then syncs all this information wirelessly to the FitBit website so that one can see real time progress.

 

[WillowJ]

anyway, it's good to have a medicine in the works. even if it's only for symptoms, having something registered for us will help.

 

[Firestormm]

anyway, it's good to have a medicine in the works. even if it's only for symptoms, having something registered for us will help.

Yep. A drug that is specifically licensed for ME would be a first. Gotta hope the buggar works in the way it is said to. First time that I am aware of in which patients and clinicians have driven drug selection based on their own experiences.

Wonder how much it will all cost - to go through all of this process of repurposing? I guess the pharma actually foots the bill if it is shown to be a worthy project for them.

In the meantime - the FDA or CFIDS - do you think they carry the cost?

 

[Nielk]

We can probably figure it out which two drugs would most patients or clinicians say are helpful? I can't be any supplement. It has to be two drugs that are currently being used by ME/CFS patients.

 

[jspotila]

I'm actually not certain the drugs are currently being used by ME/CFS patients. I don't recall that from any of the communications around the study.

In terms of footing the bill, the Association funded the study that identified these targets. I don't know who is footing the bill for the first trial - maybe Biovista and Association combined?

 

[WillowJ]

there were some drugs mentioned in the Chu/Jason survey, but I think the announcement also mentioned "trawling the literature". that is pretty diverse, so it's probably hard to guess.

hopefully they are also going off of testimony submitted to the meeting from doctors, patients, and surveys, and looking at biopathology.

 

[taniaaust1]

anyway, it's good to have a medicine in the works. even if it's only for symptoms, having something registered for us will help.

Your post which mentions "symptoms" has got me thinking more... I really want to know which ME/CFS symptoms the two drugs they have found acts on or whether they have found two drugs which work on the whole symptom complex including the post exertional PENE (their are very few drugs I can think of which could help at all with that as to do that one has to treat cause some rather then apply drugs which are only acting as like bandaides).

It would be great if someone can tell us that even if they cant currently tell us which drugs they are.
.............

Having something registered for us can only help us if we actually have that symptom(s) the drug is targeting ourselves, if the drugs they have found are antidepressants only really helping those of us who are depressed, registering those for ME/CFS patients could make things far worst as it will cause other symptoms to even be more overlooked. or a stimulant drug which is paying no attention to many of us getting post exertional symptoms and more symptoms on exercise and not just "fatigue" may also not work in the favour of many of us.

 

[Nielk]

This is from the FDA webcast of Dr. Vernon speaking about the two drugs that are being repurposed.