There are major differences between JELIS and Amarins Reduce It trial
In JELIS ..69% of the patients were postmenopausal Japanese women ...a group known for long life expectancy . In JELIS itself only 15% had diabetes and 20% had coronary artery disease
These , by and large , were not high risk patients
When you dig into the study you find areas that may be applicable to Reduce It ...as example the results from the 3,664 patients with a history of Coronary Artery disease ... 19% significant reduction in major coronary events using EPA , compared to control .
And for further detailed analysis of the patients in JELIS that are most like the patients in Reduce It ..of course you'll read " Secondary Prevention Analysis from JELIS " and report back ...followed by an analysis of the benefit in the sub group with high TG and low HDL ( typical of diabetics )
JELIS was NOT a study of high risk people ...only 20% had CAD
Reduce It IS a study of high risk patients , likely to have a CV event with 5 yrs...thus its is the high risk sub groups within JELIS that offer indications on what to expect in Reduce It
There are interesting consideration around RI interim results .
On one side you have the group that feels that once you have lowered LDL to 100 or lower on strong Satins like Crestor ...you have seen most of the benefit you are going to get ..that the . ".its all about LDL and the lower the better " crowd .
On the other side you have those that point out that in JELIS you saw benefit, regardless of the LDL level , that lower APOC3 levels ( NEJM articles ) =lower CV events ( and Vascepa lowers APOC3 by about 20% ) , AND higher blood serum levels of EPA make coronary artery plaque less prone to rupture etc etc
So we believe Vascepa has some benefit ....the Billion $ question is whether the benefit is good enough to halt the trial at interim
Secondary Prevention Analysis of JELIS
" Among the 1,050 patients with prior MI , the incidence of MCE in the EPA group ( 15% ) was significantly lower then that in the control group ( 20.1% adjusted HR 0.73 , P=.0333. NNT =19 ) "
The JELIS investigators ran the stats , Ischemic Heart Disease Journal accepted them as being reliable ...if you have a problem with it , suggest you take it up with them .
NOTE ...most in Reduce It will have had 1 heart attack or angioplasty / stent procedure
They will however have far low LDL then in JELIS .....In the 1,050 patients cited above , LDL levels were around 180 ...in RI , LDL levels have to be under 100
Thanks for all your work with the staff at the House Appropriations Committee.
Vascepa is as safe as placebo .
Everyone at risk of a CV event , should have easy and affordable access to Vascepa , while we await the Reduce It data
How do you verify what you see on flickr is not fake .
I am required to produce my ID going into the lab and again to the nurse before the blood draw.
When I pick up Vascepa from Walgreens I am again required to show my ID
But you seem willing to accept anything ...no ID required ?
How do you know its my lipid panel and Vascepa script ....only if you have an independent person like a Notary see my ID and match it to my Kaiser records
All you have to do is pick a Notary in the Marina area of SF , pay for their time , and have them agree to post their contact info so everyone can verify their findings.
There are millions of people in the US with Coronary Artery Disease ....that at least one of us should actually be prescribed Vascepa , in addition to the Satins we are on ...seems be be beyond your level of comprehension !
The target population for Reduce It are those they feel likely to have a CV event within 5yrs of starting the trial ...and who meet all the entry qualifications .
So , the most likely to event within 5 yrs are in descending order
1 ) those who have already had one MI ( heart attack )
2) Those who have confirmed angina and requiring angioplasty and stenting
3) Those over 60 who are diabetic , have a family history of CV events , have lipid disorders such as high TG with low HDL ( axis disorder ) etc
These are the patients that will benefit the most if Vascepa reduces CV events in a mostly US population.
That is why they are selected ...provided they meet the entry criteria ...LDL under 100 , TG over 200 despite optimal Satin therapy etc
The GISSI trials ..chk GISSI Prevenzione and JELIS influenced the trial design as they identified those most likely to benefit from adding DHA/EPA or EPA to existing meds
Golong ...I think you are mis reading this data
There are 2 phases to these trial
ZS Pharma Nov17th
ZSPH ...first ran an open label acute phase trial ...serum potassium was 5.6 at baseline ( note those with potassium over 6 had a drop of 1.5 mEg/l at 48 hrs ...impressive )
Those patients that achieved drops down to 3.5 to 5.0 ...were randomized into a double blind trial ...this is the maintenance phase ....
Normal potassium levels are between 3.5 -5.0
You state " again the bar for ZSPH was much lower " . that was on Nov 21st ...suggest you chk the data from ZSPH on NOV 17th again .
I think the trials are fairly similar
Golong ..suggest you do a carefull read of the NEJM reports ...re ZS-9 " Mean potassium decreased from 5.3 "... Where did you get the " lower bar potassium rates " from re. ZSPH ....mean at baseline was 5.3 ...similar to RLYP 5.1 to less then 6.5 ...not seeing a mean ......the bar for ZSPH was not much lower then RLYP from the way I read it
Hi Cy ...Ahh yes ...you work up on the hill ...spent a lot of time in the Lipid clinic there.
Re scale of variation ...do you mean the confidence interval ?
Re 8,000 subjects and 6 yrs ...important for the Power of the trial
My lay mans understanding of bio stats is some what like this .
We know that if we flip a coin 8,000 times we should get heads for about 50% of the time , and tails 50% of the time
However if we only flip the coin 10 times ...very likely we will not get a 50/50 break down ...more like a 60/40 breakdown
So if we flip it 4,800 times are we at 49 % / 51 % breakdown ...so we have high enough confidence that we are within 1% of 50/50 without having to flip the coin the entire 8,000 times
What this means for RI ..is that if we have the stats HDgabor mentioned ...at interim ...Scripts for Vascepa should jump while we await the final fine details you would like to see .
The trial would continue ...just everyone on V
Harmonize P3 results ....median time to normkalemia was 2.2 hrs with 84% of patients achieving normakalemia within 24 hrs and 98 % within 48hrs
How does Patiromer compare to that ?
Most common side adverse events during the acute phase of treatment was diarrhea ...1.2% as well as constipation , dizziness and nausea ...all 0.8%
How does Patiromer compare for the Acute phase ?
For the 28 day Double Blind randomized study ( Double blinded -the gold standard of clinical trials )
ZS-9 " appears to be well tolerated "
" All case of hypokalemia were transient and resolved after the dose of ZS 9 was reduced "
There were 14 cases of edema ( 2 of which were on placebo ) ...so of the 12 on treatment " seven case resolved or did not require treatment during the study "
Off the 14 patients with edema ( 2 on placebo ) 13 completed the 28 day study
So my lay mans view ...looks like ZS-9 is as they say ... " well tolerated "....and also acts fast... so there's the acute market .
If large scale trials show its better tolerated then Patiromer ...if cost is close ...theres the chronic market .
But as you say ( and I agree ) RLYP has first mover advantage and ZSPH has the risk of some adverse events showing up in their current longer term P3 trial.
Thanks for doing the DD ...we all benefit from exchanging informed views
Debug....I'm not short RLYP ....it will be first to market and paritomer is a lot better then SOC ( standard of care ) . Just think ZSPH is doing all the clinical work to reach a larger market and if they can produce excellent safety data ....will eventually dominate provided they are cost competitive
Chk my previous posts with Golong on this board for my other positions
By the way ...Golong has done well on some of his previous positions ...followed his posts for several yrs
Suggest you read the NEJM article I mentioned
CY ..not necessarily.
Biostats is interesting ...best if HDgabor explains it to you .
Bottom line ...if Interim shows 20% benefit with a P value of .0001 ( and a very high power ) ....then at the end of the trial it there is a very , very high likely hood that it will that it will still be 20% benefit
Johns Hopkins runs an online bio stat course in case you are interested.
HDgabor knows it better then moi
Golong ...suggest you read " A New Era for the Treatment of Hyperkalemia ? " editorial NEJM Jan 15th
Bottom line IMHO ...if RYLP was the only company developing a drug for HK ...your buyout idea would make sense BUT ZSPH 's ZS-9 ( altho 6 mths to a year behind RYLP ) has been tested in a variety of diagnoses associated with hyperkalemia in large and often double blinded trials .
Their trials also included diabetics , heart failure patients as well as reduced renal function and those using RAAS inhibitors ...so a lot more clinical data and the potential to treat a larger patient population.
That is what a buyout company is looking for IMHO
Not only that but ZS-9 works faster the patiromer and 11% of the patients on patiromer reported constipation .
Article concludes with need for long term studies for both drugs .
Of the two ...ZSPH looks more the buyout potential / partner to me ...would help fund long term trials in a variety of disease and the launching of the drug
Golong ..did you read the NEJM update. Jan 15 ...on both drugs from RLYP and ZSPH
" partimor ? appeared slow acting and may be of little use in the acute setting " ...words to that effect
Also ...as patients with chronic HK will be taking these drugs for a long time ...more extensive long term studies are required .....some concern over constipation on partimor ? ....occurring in 9% ? of patients averaged over all RLYP trials
Very definite need for stage 5 patients or acute onset ...but I expect FDA to be cautious until they see longer term data
Cy ...questions came up in Adcom on the effect of the placebo ...speculation that the paraffin oil interfered with the Statin . Expect the same in Reduce it ....which is why the results have to be great , not just ok
Reading up on Flickr.....how would you verify the photo of the lipid panel was a photo of my lipid panel ?
You need an independent person of your choosing to match my ID with my Kaiser Lipid panel same with my script
Kj4 ..and you other first time bashers
Pick a notary public in the Marina area of San Francisco ....anyone , your choice .
I will sign into my Kaiser health care account in their presence and let them see my lipid panels and I will show them the off label script I have and how much it costs me ....a print out from Walgreens .
I will authorize them to call the pharmacy and chk my cost
There is no way I can fake this ....all you and the other first time bashers need to do is chip in and cover the cost of the notary independently verifying everything for you .
No charge for my time
So you pick a notary , arrange payment for them , tell me who they are ...I'll confirm and then show up .
Mornings work best for me
You have to write at least 3 posts before I'll respond ....so for your third post ...an analysis of fish oils ( any fish oil ) when added to Statins
You could start with a summary of the GISSI trials using Lovaza ( Omacor ) and finish up with the Secondary Prevention analysis from JELIS using Epadel
Feel free to add any others you know of , that has used fish oils , added to Statins , to lower TG's
Cy ..quick follow up ...re EXEL ...chk the Bloomberg article March 26 ...refers to other cancer trials that have been stopped at interim.
Heart attacks are the leading cause of death in the US . If RI is halted at interim for more then 20% benefit ...it will be huge news.
If not ...expect a drop like EXEL
I'm not trying to spread anxiety re interim ..just trying to be realistic
Because of the placebo used ( lt wt paraffin oil ) there will always be claims that up to 8% of any benefit may be due to the paraffin oil affecting the absorption of the Satins ...and therefore making the results for V look better then they really are .
I'm not saying I agree with that , I don't, but some in the field will challenge the results on that basis.
So we need to show 18% benefit for at least everyone to agree that there is at least 10% benefit
10% agreed on benefit is not going to result in a big jump in the sale /scripts for Vascepa
However ...if interim showed a 38% benefit ...everyone could agree that there is at least 30% benefit ...and sales /scripts of Vascepa would explode.
To see what happens to a stock when the interim trial data is NOT good enough to halt the trial ...chk the chart of EXEL...see if you can pick the date of interim data release .... safety analysis was OK but efficacy analysis was not good enough to halt trial