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Ok, I thought that by "fails - to reach goal on an ACE" you meant BP was the goal.
ABT’s HCV results from AASLD abs.
One last point in addition to tolerability and convenience could be resistance, although I don't expect a combo containing 3 classes of DAAs to allow a lot of resistance still a nuke containing combo should have an even higher barrier to resistance.
ARBs - I think they are likely similar.
>angitensin + AD
This notion (that angiotensin IV peptides have pro cognitive effect) is supported by observations that inhibition of the renin-angiotensin system by antihypertensive drugs from the ARB or ACE inhibitors classes, exhibit cognitive enhancing effects. Abs. on the issue:
http://www.ncbi.nlm.nih.gov/pubmed/22330821
I think bapineuzumab is out of the game and my guess is ADCS scientists await for the biomarkers data from solanezumab EXPEDITION trials and if correlate with cognitive/functional findings, it will be the one cause as you've said safety is very important here and solanezumab has more safety data which are good.
I'm quite certain BG-12 will have a stronger ramp slope than Gilenya at 12 months, I'm not sure how strong.
Teva believes that it can file on the one year data. Of course, they may be wrong. Any delay that shortens the time between thrice-weekly Copaxone launch and generics entry is going to reduce the transition portion.
Thanks for that post.
Seems that there's a consensus regarding BG-12 becoming the biggest drug in MS in time. Aubagio doesn't look like a great choice considering its limited efficacy and tox and certainly not a 1st line drug. Alemtuzumab's safety issues will very much limit its use.
No mention of Gilenya just next gen S1P1 compounds?
TEVA thrice-weekly Copaxone
One factor I neglected mentioning is BG-12 launch, which could be more impressive than what we've seen with Gilenya, and in this case a 20% switch is too optimistic.
Assuming thrice-weekly Copaxone entry in early 2014 and generic entry in Sep 2015, and not knowing pricing but don't think a big premium, I think a 20% switch is reasonable to expect.
TEVA thrice-weekly Copaxone
Perhaps I should have clarified: time to generic launch is the key imo, because given Teva's aggressive sales promotion I think that even more than 25% of patients might switch to the thrice-weekly Copaxone but as soon as generic(s) enters, conversion will be very little.
I don't expect full transition to the thrice-weekly 40mg formulation and I think that even Teva talked about 25% or so.
Obviously the purpose of the GALA trial was to show that the thrice-weekly 40mg formulation's efficacy and safety are in the same ballpark as the 'known' profile of regular daily Copaxone, with emphasis on the convenience benefit. That's what they need to file. Converting patients is harder but as long as there's no generic version...
How about supply issue? if approved the dose should be several grams per patient per year. That's a lot of human plasma.
Maybe it is sharp-eyed :)
I see that biomarkers data will be presented in October 29th. Thanks Jbog ( #msg-80358484 ).
Lilly didn't present any biomarkers data at the American Neurological Association?
I guess you're right on the "meta-analysis of a subgroup" issue, but perhaps an ADAS-Cog change of >=3 for solanezumab in the prespecified secondary analysis of pooled mild along with MRI and biomarkers, could give them a shot with the FDA considering the highly unmet need and the good safety profile. A 3 point change seems quite hypothetical though...
Per their analysis the “best-case” scenario for change in ADAS-cog for the pooled mild AD subgroups can be from 1.2 to 1.8 points and although stat-sig this change strikes me as clinically insignificant and will surely need another trial as we've said before.
One more reason for recommending Eliquis but not Pradaxa to friends that were on warfarin for atrial fib and were not appropriately balanced or do not tolerate it, is Eliquis's lower renal excretion which is an issue with older patients (as most of Afib patients are).
I find the fact that there are several compounds (peptide/nonpeptide antagonists, RNAi, or anti-CXCR4 mAb*) targeted to block the SDF-1/CXCR4 complex in clinical trials good for BLRX in the sense of validating the MOA.
http://www.ncbi.nlm.nih.gov/pubmed/22376154
* BMS-936564 isn't mentioned in the abs.
In any case these bleeding issues with Pradaxa should help Eliquis in AF.
Pradaxa bleeding risk may be associated with a polymorphic gene
http://www.escardio.org/congresses/esc-2012/congress-reports/Pages/711-1-RELY-Genetics.aspx
PSTI: a third similar case:
http://maya.tase.co.il/bursa/report.asp?report_cd=762135-00&CompCd=1569&Type=Pdf
Mentor made a bid to acquire MRX in 2005 and was itself acquired by JNJ in 2008.
New anticoagulants
MRK's lead BACE inhibitor - MK-8931
Sounds like MRK has big expectations for this candidate. I thought they will do a smaller phase II for safety and biomarkers data only. This big trial should also be powered for efficacy. It isn't in clinicaltials.gov yet, guess it will start later this year.
Not sure this work from deCODE genetics was posted but anyways the protective mutation, or the rare genetic variant (cheers Vin), found in the APP gene bodes well for BACE inhibitors
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline
Jonsson et. al., Nature. 2012 Aug 2;488(7409):96-9.
http://www.ncbi.nlm.nih.gov/pubmed/22801501
Abstract
The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-ß precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease ß-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the ß-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.
Sorry, I wasn't clear. When I wrote that LLY leads the way, I meant in the BACE inhibitors space not all AD field.