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More informabout Xadago (safinamide)

7 posts in this topic

About Xadago (safinamide)

Safinamide is a new chemical entity with a unique mode of action, including selective and reversible MAO-B-inhibition and blocking of voltage dependent sodium channels, which leads to modulation of abnormal glutamate release. Clinical trials have established its efficacy in controlling motor symptoms and motor complications in the short term, maintaining this effect over 2 years. Results from 24 month double-blind controlled studies suggest that safinamide shows statistically significant effects on motor fluctuations (ON/OFF time) without increasing the risk of developing troublesome dyskinesia. This effect may be related to its dual mechanism acting on both the dopaminergic and the glutamatergic pathways. Safinamide is a once-daily dose and has no diet restrictions due to its high MAO-B/MAO-A selectivity. Zambon has the rights to develop and commercialize Xadago® globally, excluding Japan and other key territories where Meiji Seika has the rights to develop and commercialize the compound. The rights to develop and commercialize Xadago® in the USA have been granted to US WorldMeds, by Zambon

*Information provided by the FDA Website

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Thanks for the information about Xadago.  It sounds like it has potential that could reduce dyskinesias and providing a longer "on" time.  It seems to be a beneficial drug for the Parkinson's population that needs the Sinemet on a frequent basis that induces dyskinesia.  My husband was in that population.  He was also on Amantadine that reduced his tremors until that no longer was effective.  He has now had the DBS surgery which is a great blessing and given him the gift of quality of life.  I know many Parkinson's patients who don't qualify for the DBS surgery and continue to suffer from tremors and dyskinesias.  Do you see this drug as being an especially helpful therapy for these patients and also when my husband's DBS benefit is reduced due to the progression of the Parkinson's?  Is this drug even on the market yet?  If it is, do I dare ask how expensive it is?  Thanks!

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How does the mechanism of action of Xadago compare to how Azilect works?  Does Azilect modulate glutamate release as well or does it work some other way?  One reason I'm wondering is that I was unable to take Azilect as it aggravated my migraines.  However, I do take topamax for migraines which I thought affected/calmed down glutamate in some way. So I'm hoping I may be able to tolerate this new drug if the mechanism of action modulates glutamate and therefore might not aggravate my migraines.  (The chemistry is really over my head but I sure would like another option!). Thank you!

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Carruthers,

This medication was just approved by the FDA and is not on the market in the United States. It have been available in several parts of Europe and the U.K. for the past several years. It is known by it's generic name "Safinamide."

This medication can be beneficial for Parkinson's patients who have or whom have not had DBS surgery and are on a carbidopa/levodopa therapy, which is required at this point for the use of Xadago. If at this point your husband is currently taking a carbidopa/levodopa therapy and having issues with "off" time and lack of "on" times, this may be a possible additive to his medication regime when it becomes available.

I hope this helps and keep me posted.

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Market,

Unfortunately the Mechanism of Action (MOA) of Topamax on migraines is not fully understood and was basically noticed when studied on seizure activity. It is known that Topamax stabilizes electrical nerve acticity by modulating two neurotransmitters. In seizure activity it is seen that the neurotransmitter GABA (which is a calming neurotransmitter) is decreased and Dopamine and Glutamate (which are excitatory neurotransmitters) where low. Topamx stabilizes this situation by mudulating the GABA, Dopamine, and Gluamate back to the "normal" levels. It is theorized that this Glutamate antagonistic (blocking) activity may the reason Topamax works on migraines.

When it comes to the difference between Azilect and Xadago  it is a very in depth and somewhat difficult to explain, but I will attempt to. I will show their individual effects and actions in quick bullet point form so you can see the difference instead of me trying to explain it.

Azilect:

Monotherapy: Can be used alone or with other PD medications.

Selective MAO-B Inhibitor (Monoamine Oxidase B Inhibitor)- Monoamine Oxidase Enzyme breaks down Dopamine.

*IRREVERSIBLE MAO-B Inhibitor.

Mechanism of action primarily to increase Dopamine in the nervous system of the brain.

Indicated uses: Reduce PD symptoms of stiffness, poor muscle control, tremors, and spasms.

May have Neuroprotective properties.

Xadago (Safinamide):

Adjunct Therapy: At this point should ONLY be used in conjunction with Carbidopa/Levodopa therapy.

Selective MAO-B Inhibitor (Monoamine Oxidase B Inhibitor)- Monoamine Oxiidase breaks down Dopamine.

*REVERSIBLE MAO-B Inhibitor.

Duel mechanism of action to increase Dopamine AND stimulate Glutamate release. 

Indicated uses: Reduction of "off" times in patients with PD.

May have Neuroprotective properties.

As you can see above the two major differences are (1) Reversability and (2) Glutamate release. I will do my best to describe the differences here.

Irreversible .vs. Reversible:

Irreversible: MAO Inhibitors such as Azilect (rsagaline) connect to the Monoamine Oxidase Enzyme with a bond that is not able to be broken. This means that the combined product (Azilect + Enzyme) is irreversvible and is not able to do anything. This non-functioning product (and enzyme) activity is blocked until another enzyme is produced.

Reversible: MAO Inhibitors such as Xadago (safinamide) connect to the Monoamine Oxidase Enzyme with a bond that is able to be broken. This means that the combined product (Xadago + Enzyme) is reversible and able to be separated so that the enzyme can break the product into their individual pieces and the enzyme can breakdown the individual active piece (in this case Xadago) so it may continue it's activity.

Glutamate Release:

As stated above, Xadago has the added mechanism of Glutamate release. Some Dopamine receptors aid in Glutimate release while others decrease it. This all depends on where in the brain theses receptors. In the Substancia Nigra, where the Dopamine issue is in PD, Glutamate stimulis coming from other parts of the brain trigger a dopamine response. The Sunstancia Nigra is in the Basal Ganglia and the stimulus of this release is directly responsible for muscle tone and muscle movement. This Glutamate released in this area will then help with maintaining muscle tone and movement without the use of Dopamine.

I guess to answer your question that "if you had a reaction to Azilect will you have one to Xadago," is it is mare than likely that you will have the same reaction. Since I have not seen all the available data on the case studies, that is my best educated guess.

People say,"A picture is worth a thousand words." Some people prefer the picture. I, on the other hand, prefer the thousand words.

I hope this helps and keep and keep me posted.

 

 

 

 

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Noah,

If you red my response to Market above that should hopefully answer your question. A quick answer is that is that "yes" the are both MAO-B inhibitors, but Xadago has an extra Mechanism of Action. Azilect Can be used alone or in combination with other PD medications to releive a variety of symptoms. Xadago is not used as monotherapy, and must be used in conjunction with Carbidopa/Levodopa therapy. It is only, as of today, to be used to help decrease the "off" time in individual's with PD.

I hope this helps.

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