Paula, this is my guess, that Merck is cooking up a carbi/levo product using Depomed's AcuForm technology. Who do I call to check that out? If there is a clinical trial, it has to be registered with the FDA, so I could just check the list of new trial applications or recently approved trials.

My guess is that Merck is keeping what Sinemet (CR in particular) they already have to satisfy the US market where it brings the highest price, and releasing just enough to Canada and the UK, possibly a couple of other smaller markets, to keep the pipeline trickling. This will continue until their new AcuForm carbi/levo is tested (about 2012?). Everyone else will have to catch as catch can.

There; is that paranoid enough?

Robert

If you check out the Depomed link in the above post, then click on "our pipeline" you will see that they began Phase I tests on DM1992, their formulation of carbi/levo using their AcuForm technology. They seemed to stop work on DM1992 about the time Merck licensed AcuForm.

There was also a description of this in a 2009 MJFF news letter I found when I googled Merck and Januvia and AcuForm.

Did Merck make a deal with Depomed to not persue DM1992 so Merck could replace Sinemet CR with the better AcuForm carbi/levo which did outperform generic Sinemet CR in their tests (9 hrs theraputic levels vs 7 hrs for generic CR)?

I hope SOMEONE is working on it!

Good detective work!
There is more info on DM 1992 in the Parkinson's Pipeline project data base.
Go to www.pdpipeline.org. on top menu click on "Database access"
Also on the Scorecard page if you click on the heading "Treatment class", the list will resort. scroll down to "Levodopa", there are a number of companies working on substitutes for Sinemet. Good idea to look for collaborations with Merck.

This was posted Jan 15, 2010, many months after Merck announced global shortage. http://www.apotex.com/global/pubadvi...o_levocarb.pdf

ALL of Canada's production was by Apotex; it ALL shut down, increasing severity of the crisis, but APotex makes generic, and Bristol MS sells sinemet in Canada, Merck does not,

Formerly made in Canada; now Canada has to import, reducing what is left for other countries. Guess that is the price the Canadian Government had to pay to keep supply coming.
What is deal between Merck and Apotex? Both cut production deliberately.

I think you may be correct about this. Merck has a history of trying to control the market . They own the patent for methylfolate, which they used to sell to OTC vitamin houses.
They removed their product from OTC sale for a few years to give a push to RX Deplin and Metanx, and Cerefolin.
I was very vocal about this, and it appeared on the net in other blogs. Soon Merck caved in and now is selling to Solgar at least.
But they are not selling to Folast apparently since that product is under fire for having a racemic mix of methylfolate and not the L- form like Merck's.

There is another company trying to get the FDA to put P5P (an OTC activated B6 on RX only), like Merck tried with methlfolate.
Here is a link to the FDA letter to the public about that one:
http://neurotalk.psychcentral.com/sh...ight=pyridoxal

Never underestimate Big Pharma.

Also BTW the generic levodopa/carbi long acting has always been rather poor in its delivery. It has been recalled in the past.
It is also possible it is going to be removed for that reason, and the manufacturer was given warning etc. But I too agree that it is probably a manipulation by Merck.

When drugs appear in other countries, they are often licensed from a parent maker... they do not necessarily "make" a product. Many generic houses put their name on things, but inside the bottle, the imprint of the tablet/cap is of another company. The softgel dosage forms often go back to one manufacturer, for example:
http://www.pharmcast.com/BuyersGuide...nerComInfo.htm

Bristol Myers Squibb is a very complex merged company.
It is the FDA holder of patent for Sinemet extended release currently according to the FDA Orange Book.
(this drug used to be made by Endo-Dupont).
Sinement has passed thru many hands in its history.

Today, patents are sold to other companies all the time. It is very hard to even understand these movements anymore!
Levothyroxine has been thru 3 major makers, including the current Abbott.

You can spend hours on the net trying to find out who really makes the generic version of Sinemet.

What may be happening here, is that the original owner of the patent to MAKE the initial powder form for either levodopa or carbidopa is not selling to Apotex anymore. I suspect Apotex buys the product from Merck, or BMS.
Since Apotex is not talking.... it must be something that would upset people. IMO.
http://www.ctv.ca/servlet/ArticleNew...128?hub=Canada

An example of generic supply of original powder...
Soma, the muscle relaxer is the brand name owned by Carter/Wallace which became Medpointe which is now called Meda. They are the only maker of the raw product, and sell this powder to generic companies.
This is probably one reason they stay in business so long, with no really other drugs to sell, or things in their pipeline. They are a very odd example of supply and demand! (at least this was true up to the last few years --when I found this out-- for all I know they have sold that patent to someone else!)

Some generic companies DO buy the patent to making the raw drug..Mylan has been known to do this. They then jack the price up like 1000% to cash in on that exclusivity!

Looking at the Orange Book at FDA.gov reveals who can sell extended release Levo/carbi in US.

This is really a complicated business issue. Much seems to be information not available to the public easily.

Robert - to quote the title of Andy Grove's book:

"Only the Paranoid Survive."

thank you ,
paula

Mrs. D. said:
Since Apotex is not talking.... it must be something that would upset people. IMO.

Will 2849 said: My personal opinion is also that I think it unlikely that Merck decided to create a shortage just to boost the demand (and their potential for profit) for Sinemet. My personal opinion is that there was most likely another reason for Merck's decision and I would like to know what that reason is… While I would suspect that I would be supportive of Merck's decision to alter their supply chain like this, Merck may believe that it is in a situation where they would be better off keeping their reasons to themselves.

Stealth PD researcher named “Anuket” http://anukets-crusade.blogspot.com/ pointed out that, throughout the on-going controversy and lawsuits about Mirapex and other agonists causing compulsive gambling and hypersexuality, it was always the agonists at fault, never levodopa itself.

Then, with no publicity and not a trace of scientific evidence (unless they are hiding the evidence), in late 2008, the Sinemet product insert suddenly was changed, to say that sinemet causes the same problems of compulsive behavior. Almost word-for-word the same warning as for the agonists.

And the product warning contained a new, ominous paragraph that I don’t remember being there before:
Melanoma
Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, is unclear.

Sinemet Product insert:

http://www.accessdata.fda.gov/drugsa...555s069lbl.pdf

So, is this a case of: “We warned you, but you went to see your doctor, who prescribed you these horrible drugs that we, Big Pharma, were trying to take off the market, but we had no choice but to fill the prescriptions.”
It is amazing that we have to try to guess the truth. My Toyota got recalled and the Prez. of Toyota was dragged through the grinder in Washington. But my drugs disappear and there is a conspiracy of deception to hide the truth.

I think the carbidopa portion of the Sinemet mix, is problematic in other ways too.

Carbidopa (which is sold in Europe to enhance 5-HTP levels in the blood) can cause a scleroderma type illness when used that way or with tryptophan. This is a skin condition as well.

The melanoma connection is found on various drug information sites like this one:
from http://www.drugs.com/pro/carbidopa-a...a-tablets.html

Whether this is because of poor Vit D status or the drugs, I don't think anyone knows for sure. But melanoma is turning up in very young otherwise healthy people, in their 20's even! So it is a multifactorial issue at this time IMO.

I enquired at the highest level I could here in the UK and this is the response I got:

"The problems have arisen due to changes in the source of supply of the active ingredient. As you may be aware, pharmaceutical production is complex and highly regulated, and companies need to generate supporting data in order to obtain approval from the Licensing Authorities for any such changes. This can be a lengthy procedure.

MSD have assured us that they are doing all they can to make sure that there is a return to normal supply as soon as possible. In the meantime they are managing their global supply carefully taking a number of factors into consideration. Priority is being given to maintaining continuity of supply in those countries where there is no generic alternative, so that patients can continue their treatment.

All presentations of Sinemet are currently available in the UK, although it is possible that disruptions to supply may occur in the coming months. The manufacturer of generic co-careldopa tablets has confirmed that it has adequate supplies of this product in stock.

On a more general note, we share your concern about shortages of medicines. These can occur for a number of reasons; as well as difficulties in obtaining raw materials, companies can experience regulatory problems or unexpected manufacturing difficulties leading to batch failures. The Department of Health and the Pharmaceutical Industry have produced joint "best practice" guidelines which are designed to help minimise the impact of medicine shortages on patient care. The guidelines give advice to companies on the management of shortages and encourage early exchange of information with the Department. This allows consideration of the options that are available to help ensure that patients continue to get the medicines they need."


There is only one other body to approach at this level, which I have done already, but not yet received a reply, and that is the All-Party Parliamentary Group on Parkinson's. If the possible shortages mentioned do materialize later this year or in 2011, having made initial enquires, I will be in a position to request that the matter is raised in Parliament as a matter of urgency.

While the above does not explain WHY Merck has had to change it's source of supply it does shed some light on what is happening in the UK, and how Merck is adjusting supplies, especially the situation in Canada and Australia.

I am very interested in RLSmi's information on Acuform, it figures on the website that was launched when Merck went through it's recent merger with Schering Plough, and the further info on DM1992 looks to back that up. I was very interested to see that Sinemet was not listed as one of it's products. This would also indicate that there is some change in their agenda.


Also very interested in Mrs D's statement,

"the generic levodopa/carbi long acting has always been rather poor in its delivery. It has been recalled in the past.
It is also possible it is going to be removed for that reason, and the manufacturer was given warning etc."

The fact that the generic is/has been poor in delivery needs to be communicated to professional health bodies, as a matter of concern.

There is also a variation in affect between licensed branded Sinemet, The Merck version is noticeably different to the Bristol-Myers-Squibb. It is unclear whether this is a difference in matrix, affecting availability, or a difference in quality of the active ingredient. The key to this is that the patient CAN tell the difference.

Information on differences in different formulation should also be made available to patients if there are any questions about their treatment that might relate to dosage and fluctuations that could be traced to this issue. (An example of this would be a note to prescribing doctors in the British Formulary, or other national drug directories.)

Untangling the production/supply/distribution lines globally is a large job, not one that is likely to all show on the internet. However this is an essential drug, and it would do well to find out whether it is listed as such on national drugs registries, and if the generics are listed along side branded sinemet. If so then a consistency of product should also be expected.

In terms of new formulations of slower release, longer acting dopa, it seems to me that is a cosmetic tinkering with formulation so that a product can be marketed more effectively. It does not actually offer the patient anything that different, and may even be detrimental, witness the amount of people for whom CR does not work effective, or stalevo is unmanageable, and who in the end revert to plain old sinemet.

I find the research on exercise and PD of much greater interest, and potential benefit than acuform.

Lindy