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Biotech / Medical : Celgene-CELG -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (285)	2/16/1999 12:58:00 PM
From: Biomaven	Respond to of 804

Rick, I assume that what they mean is that, for a given dose, the side effects are similar (like albuterol/levalbuterol). However, you would be giving a lower dose than w/ the racemate, so overall side effects should be lower. Remember this was a pretty small trial (around 30 people), and so they can't be expected to be able to claim too much from it. I'm sure Miljenko will have something more informative to say. Here's the announcement from Biovail: d-MPH is the pure and active form of the marketed raecemic version of methylphenidate, offering advantages such as reduced doses, diminished metabolic load and the possibilities of significant reductions in adverse effects and abuse potential that tend to be associated with the use of the raecemic form. Chiro from their small published study (12 patients) also claim only dosing advantages. Here's what Chiro has to say about patents: This product is protected by an estate of nine internationally filed formulation, use, process and composition of matter patents, seven of which have been published, so that the Chiroscience R&D/Medeva collaboration is in an excellent competitive position. Patent position is quite murky - there's also the FDA regulation giving a few years of exclusivity to single-isomer improvements to factor into the equation. Peter

To: scaram(o)uche who wrote (285)	2/16/1999 9:52:00 PM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 804

Rick, Peter and others: First few words on racemic methylphenidate (racemic Ritalin) pharmacology and side effects. (+)-R is ~10 times more active than (-)- R. Also, (-)-R has week anti-obesity property, loss of appetite, something to do with seratonine level??? Their main metabolite is acid, hydrolyzed methyl ester, and rate for this clearance is higher for (-)-R than (+)-R. So, if racemate is administrated and higher more frequent doses is needed buildup of the main metabolite do increase. This metabolite interact with several drugs (reduce their effects or inhibit their metabolisms). For instance hypotensive, anticoagulants, anticonvulsants, antidepressant,... Today total Ritalin prescription is ~equally distributed between children and adults (as ADD and Narcolepsy, as well as in combination with other CNS drugs for some disorders). Regular R therapeutic effects last ~4 hr, while SR formulation max 8 hr. It is not recommended for late afternoon or night administration because may effects sleep mode. <<its side effect profile was comparable to its racemate >> No additional adverse reaction because of the increased (+)-R plasma level. When CNS drug is issue, always keep in mind that each enatiomer may be responsible for different benefit as well as different side effects, which can become evident only after chiral drug is administrated. <<Why test a product where there is no clinical benefit?>> No additional side effects, clinical benefit (increased positive and/or reduced negative) has to be confirmed/determined. <<Boy, this release really threw me off..... I must have missed some important stuff...... why is it necessary to run separate trials in Canada? When did the pivotal trial start in the U.S.? >> If they want to file NDA in Canada, first they have to file IND for ICE. Trial in Canada ( I do not know which type it is, but will guess that it may be PII/III; two-three different doses) will complement ongoing trials in US, for US and Canada NDA. Also, I guess, Biovail will be financial sponsor for trial. So, by one shot in Canada they are killing two rabbits. Al in all, Biovail statement (thanks Peter): << d-MPH is the pure and active form of the marketed raecemic version of methylphenidate, offering advantages such as reduced doses, diminished metabolic load and the possibilities of significant reductions in adverse effects and abuse potential that tend to be associated with the use of the raecemic form. >> is probably too strong at this point. However, I think that (+)-R (more pronounced as pulse-release formulation) is probably correct answer for future. Today major R prescriptions are immediate release, not SR-formulation, so (+)-R will have its place in market, if trials hold. Hope this help. Miljenko PS: I too am focused on T and SelCIDs (bit more on SelCIDs), but bit of progress news never hurt.