Is there BH4 supplement/medicine?

[Maz01]

FYO: the reason BH4 is expensive and only available without prescription in small dose tablets is because BH4 was given orphan drug status in 2002, giving specific companies the exclusive right to sell BH4. Biomarin and Merck Serono has this right, and they sell their BH4 (trade name Kuvan) in 100 mg tablets.

But all the other sources of BH4, such as Pteridin-4 from Ecological Formulas, are at low doses (eg 2.5 mg), sold as "homeopathic" formulations.

However, this BH4 orphan drug status is due to expire in June 2015, ending the exclusivity, so the price of BH4 will hopefully drop, and the availability and dosage of BH4 will hopefully increase.

I recently wrote to several supplement manufactures pointing out that BH4 will be classes as a supplement after June 2015, and that they might consider adding this supplement to their range.

Hello,
I'm new here and am having huge health issues that all can be traced back to running out of Bh4 in April 2015... Do you have any idea what's going on with the Bh4 avalibility? I have called my compounding pharmacy and they cannot get it and don't have any idea when or if they ever will.

 

[trsnorth]

BH4 has been a life saver for me. I even went back to work part time until pteridin-4 went out of stock. I had to quit my job. Citrulline malate is ok. I can least function some what and helps with the muscle spasms/pain.

I have a functional medicine doctor who specializes in MTHFR so I have my MTHFR working pretty good but it is not enough to over come my bh4 defeincy. I have a1298c +/+. My CFS is so bad that the cfs protocol doesn't work well without bh4 supplement.

Has anyone heard why bh4 is always running out and takes forever to manufacture more? I understand that more people are trying it.

 

[knackers323]

so the best place to buy it without prescription is.......?

 

[trsnorth]

The best price is Pteridin-4 from Ecological Formulas. Unfortunately it is out of stock. There are rumors that there should be some in december of this year.

 

[knackers323]

thanks @trsnorth I was hoping to find something with a higher dose

 

[trsnorth]

thanks @trsnorth I was hoping to find something with a higher dose

There isn't any without getting a prescription for kuvan. I feel for you. I have the same need. If I have it at a higher dose then I can be employed again.

 

[knackers323]

surely there is a place online that sells it. have you tried a chemical supplier?

 

[malk]

surely there is a place online that sells it. have you tried a chemical supplier?

Sure there is. As it is outlined in this thread there are chemical supplieres. I know of at least two. Schricks and caymanchem.

But there are not recommendable in my opinion (as also discussed here previously) due to several reasons.

One reason seems that high doses may have serious side effects. High doses may interfere with metabolism (I found a study once, but can not find the link anymore), I have listed and compared the offers once more:

Kuvan:
+ Official medical product
+ available
- prescription needed
- expensive if you get along with lower doses, because one tablet is rather high and might be a waste of money if you dump the rest. To my knowledge BH4 oxidises very fast and you can not store (let us say) 3/4th of the tablet savely for the following days (please correct me if i am wrong).
+ apparently stable in the tablet (no cooled shipping required)
+ available in pharmacy (no shipping costs) , at leased supposed to (still seems hard to get).
+ price: Euro 30,- per 100mg - so it is actually the cheapest option!!!

Schricks:
+ available
+ company apparently long on the market, sold tablets bevore others got the exclusive right to do so, so I assume it is save for humans
- not for human use approved (but I guess that is stated mainly for legal reasons, because not allowed to sell it for humans)
- some got serious side effects with higher doses
- not storable: one ampule contains 1.000mg, once opend it will oxidise quickly but you would have to store the rest over weeks - Schricks itself recommends storage at -20degree celcius (an I assume in the sealed ampule???)
- there are smaller ampules 100mg each but they cost way more
- might be blocked by customs when imported from Swiss because it is a drug
- price as per 1000mg ampule: USD 35,- per 100mg PLUS customs and VAT PLUS shipping (cooled & express), so let us assume around 45,- USD without shipping. Which are currently Euro 42,- (depending on exchange rate).
- price as 100mg ampule: USD 121,- PLUS customs, VAT and shipping
+ price as per 5000mg ampule: USD 23,- PLUS customs, VAT and shipping
-/+ price might be negotiable if many people order at once
- has to be shipped cooled and express, which is expensive and would it make difficult to be split and forwarded in case many order together

caymanchem:
- all problems are the same as with Schricks
- price per 100mg: 100mg Euro 194,- since it is within Europe no customs for Europeans but I assume VAT has to be added on top, so I assume 220,-

Ecological Formulas:
+ no prescription needed
+ lower doses (I feel fine with around 2,5mg to 10mg a day)
- has to be shipped & stored cooled. I tried it myself, the cooling package lasts for aroud 10 to 24 hours so you would need express shipping in wintertime to optimise shelf life
- I assume not very stable. One capsule has an antioxidant (Vitamin C), which is good, but no sealing like an ampule, so I assume it will degrade quickly.
- price: 100mg Euro 67,- (at least, depending on supplier)
- out of stock regularely and for a long time

These are my 2cents. Anny corrections and additions are appreciated.

 

[aquariusgirl]

If anyone comes up witha doc who is willing to Rx Kuvan off label pls let me know.

Is it a hard tablet or ocpasule ?

Also how come the manufacturers haven't clued on to this off label use? I know the autism parents are desperate to get their hands on BH4.

 

[knackers323]

@malk are you still seeing good benefits from the bh4?

any ideas why the ecological formulas remains out of stock everywhere?

thanks

 

[malk]

@malk are you still seeing good benefits from the bh4?

Can't say, because out of stock for a while.

 

[trsnorth]

I will mention Kuvan comes in a 100mg powder to be mixed with water or juice. This was developed for childern with pku. Kuvan is stable in the refrigerator after mixing in liquid. You use a non needle syringe to measure out the amount needed.

Remember Kuvan is synthetic for better stability for production AND patents. I wouldn't take Kuvan by body weight as they did in the trails.

I personally start with 3mg twice a day and go from there. I know I need about7 to 10mg of BH4 (pteridin-4) a day to feel normal.

The problem is how equilivent is natural vs synthetic.

 

[malk]

Thanks for your clarification. Didn't know that it is stable in the fridge. How do you know? By trying? Because Kuvan manufacturer seems very secretive.

Also I have read often that it is synthetic produced but does that mean it is different to the natural product? I can't find any solid explanation.

 

[trsnorth]

The company making Kuvan is walking a fine line with FDA. They will never verbally give info beyond the use for pku BUT they are happy to send info on the product and research done in other countries legally.

Finally I uploaded them. This is what they sent to my doctor. I had to go to my computer instead of my android tablet to get it to work.

The biggest mistake I can see with the trail test using Kuvan for people with MTHFR/A1298C +/+ is they didn't look at the big picture. I was fortunate that BH4 was a huge impact in my life the first time I taken it while my doc was working on my CBS +/- down and up stream plus rebalancing my zinc and copper ratio. I feel MTHFR must be addressed where need be before given Kuvan by body weight. (rolls eyes). The advise I can give you is to use the powder from of Kuvan so you can dilute it to a lower dose than they did in the trails. I am thinking getting the prescription from my functional medicine doc and start with 2.5mg twice a day and work up from there.

Remember you need vitamin C with it. I would suggest Liposomal vitamin C. It explodes in my body every time I take it in a positive manner. It was going to say how expensive it is but it looks like it went from $80 to $30 per bottle The bottle has 30 servings. I learned I would be doing better energy wise if I could take it 3 times a day and then drop it down to twice a day after a couple months.

Good luck and enjoy a nap
Red

 

[malk]

Many thanks, I will read through the documents

 

[kyzcreig]

@Hip

It's 2016, does that mean BH4's orphan drug status has expired - where can we check that? What stops another company from sponsoring it again?

 

[Hip]

It's 2016, does that mean BH4's orphan drug status has expired - where can we check that? What stops another company from sponsoring it again?

I presume so, but you'd need to check with the FDA, who are the organization that approves orphan drug status.

I wrote to a number of supplement companies explaining to them that the orphan drug status was about to expire, and asked whether they would consider bringing out a BH4 supplement, but none replied to me. One of the difficulties is that BH4 has to be refrigerated at all times.

 

[kyzcreig]

I presume so, but you'd need to check with the FDA, who are the organization that approves orphan drug status.

I wrote to a number of supplement companies explaining to them that the orphan drug status was about to expire, and asked whether they would consider bringing out a BH4 supplement, but none replied to me. One of the difficulties is that BH4 has to be refrigerated at all times.

Here's the latest news I found on the subject:
http://www.nasdaq.com/article/biomarin-dr-reddys-agree-to-settle-kuvan-patent-litigation-cm522128

I've just emailed the FDA so we'll see. I'd like to buy it from that Swiss lab. Worst case I can have my European cousins mail it to me.

I would consider making my own supplement if the patent has expired. Or maybe just making it available here if there's enough interest. Ecological formulas is unfortunately always on backorder.

 

[Hip]

Here's the latest news I found on the subject:
http://www.nasdaq.com/article/biomarin-dr-reddys-agree-to-settle-kuvan-patent-litigation-cm522128

From that article:

BioMarin expects net sales of Kuvan in the range $210 million - $230 million in 2015.

BioMarin are certainly making a tidy sum of money from their exclusivity on BH4.

I've just emailed the FDA so we'll see.

I'd be interested in hearing their response.

I would consider making my own supplement if the patent has expired.

How would go about doing that? As far as I am aware, you can legally do that anyway: I don't think a patent legally stops anyone from making a product, just stops them selling and profiting from it.

 

[kyzcreig]

I know right, they didn't even invent anything. One of their guys read about KPU then they claimed BH4 and marketed it like mad.

Ok I received a reply from the FDA saying the orphan exclusivity was up:

Dear Alex,

According to our Orange Book Database, sapropterin has been issued the following exclusivities with the corresponding expiration dates:

Orphan drug exclusivity - Dec 13, 2014

New Patient Population exclusivity – Apr 23, 2017

Pediatric exclusivity – Jun 13, 2015

Pediatric exclusivity - Oct 23, 2017

You may find this information by visiting http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm, searching for the drug (sapropterin), clicking on the application number, and then clicking on ‘View Patent and Exclusivity Info.”

Best regards,
RL
Drug Information Specialist
Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration

This communication is consistent with 21 CFR 10.85(k) and constitutes an informal communication that represents our best judgment at this time but does not constitute an advisory opinion, does not necessarily represent the formal position of the FDA, and does not bind or otherwise obligate or commit the agency to the views expressed.

Here is the patient and exclusivity info, you can see the 4 exclusivities he mentioned at the bottom.
http://www.accessdata.fda.gov/scrip...fm?Appl_No=022181&Product_No=001&table1=OB_Rx

Now pediatric exclusivity only applies to children. And I'm not sure what New Patient Population exclusivity is exactly. From what I could tell it applies to clinical investigation and application of the drug into patients of other illnesses.

I think I'd just sell it on the internet e.g. Amazon.com and see what happens. If they send me a cease and desist then I'd stop. Or maybe not. I have a lot of lawyers in my family.