Golong Part 2 .
Re IV Insulin " The onset of action is within 20-30 minutes and the duration is variable , ranging from 2-6 hrs "
So its a temporary fix with its own set of risks " Patients with acute kidney injury and CKD are especially susceptible to hyoglycemia ( even if the insulin is administered with dextrose )
These patients will still need either Patiromer or ZS-9 ....either with or after their Insulin IV.
Here again ZS-9 wins because of faster onset of action .
Especially in an emergency situation ...and IV Insulin is this setting is an emergency ...the Md's want to see serum Potassium lowered the fastest and maintained there .
So ZS-9 will certainly be used in an Acute setting.
In Chronic care it will come down to which maintains normalized Potassium the best / lowest side effects and cost of monthly dose.
Golong ..this may have to be in 2 posts .
Re your "good doctor " on RLYP.. He is correct in that speed of action is not critical in Chronic care . What is critical in Chronic care is which drug maintain normalized serum Potassium the best with the fewest side effects ...I'm betting thats ZS-9 at 10 mg dose . But we won't know til a possible early look at long term ZS-9 data in Nov 2015
Regarding Acute Care
The guidelines for action are well documented if you research Nephrology sites enough.
Quote " The faster the rise in the potassium level , the higher it has reached , the greater the evidence of cardiotoxicity , the more aggressive the therapy should be.... ( dialysis in patients with renal failure if possible otherwise IV insulin )
If a patient has only a moderate elevation in potassium levels and no EKG abnormalities , excretion can be increased by using Kayexelate or diuretics ."
My wife tells me that in moderate elevation situations, Patiromer will immediately replace Kayexelate and that ZS-9 will replace Patiromer because ZS-9 is faster acting .
They want to administer the drug and have the patient stay around for 2 hrs for a follow up blood test before releasing.
Well Frenzy , you are in good company .
JL ( on IHUB ) is now aiming for a 50% benefit . So if that comes true , a halt at Interim is a done deal.
Should say IF that comes true .
So really your 19% estimate of benefit ( if thats what it was ) is actually quite conservative ..:)
Good to read your post tho .
Informed debate seems pretty rare here these days.
Golong You know I appreciate your opinion .
You have been right regards CEMP and all looks good for great end of yr data there.
With regards ZSPH and RLYP
I'm a retired CEO ...small corporation
Make the case to me on why I should buy RLYP ( the company ) if ZS-9 works faster , maintains normalized Potassium levels better and is cheaper ( because of lower dose load )
ZS-9 is faster acting , if it also maintains lower K levels better and is cheaper ...I don't see anyone buying RLYP.
Hmmm Frenzy ..if life was so simple . Hope You don't mind a little push back as you presented an interesting opinion.
1) you realize that if we only get the 19% final improvement you cited re JELIS , Reduce It will not be stopped at Interim.
2) Reduce It is being run with optimal dose Statin ( mainly Crestor and Lipitor ) , rather then the mild /medium dose Simivastatin used in JELIS
3) JELIS was 68% post menopausal Japanese women ....There are no Japanese women in Reduce It.
Now I think Reduce It will show benefit because of the large number of Russians and Ukranians in the trial ( 40% of the males in the Eastern Block have a CV event by age 50 ) ...This population is known for their high meat diet / lack of exercise life style and would be expected to have a very low EPA /AA ratio...thus prone to CV events
So IMHO Reduce it is a distant cousin of JELIS rather then an identical twin.
Hi Golong ....good to hear from you ( yes I mean that )
Will ZS-9 dominate the world market ?
Depends on the following because we know which acts the fastest. ( lets assume that mild adverse events is the same for both right now )....So we need to know
1) Long term safety data and maintanence of normalized serum K levels
2) cost of the products.
Re 1) We know that 20% of those on Patriomer with the long term to date ,revert to hyperkalemia .
Will ZS-9 at 10mg dose do better then that .?
The earliest we will find out is late Nov 2015 when the Co is supposed to release data on the first 200 of their 750 patient long term trial
Re 2) Cost of product per 1 mth dosing . We known ZS-9 at 10gm dose is supposed to be about $600 a mth to the payor ( insurance Co ).
Do you have any information on what Patiromer will cost per mthly dosing ??
So ...if ZS-9 works faster , maintains lower serum K levels better and is cheaper ( less drug required )....What is the case for a Nephrologist or Cardiologists prescribing Patiromer ...or an Insurance Co paying for it ....once ZS-9 is approved ?
IMHO The market is forward looking ..chk the price trends of both Co's
As a follow up . We know that ZS-9 is supposed to cost payors about $600 a mth.
Any idea what a monthly dose of Patiromer might cost ?
So close to approval and we don't seem to know what its expected to cost ?
The ZSPH catalyst , is long term data that supposed to be reported on the first 200 patients ( of the 750 enrolled ) ...about a month after RLYP gets FDA approval.
We know which drug works the fastest
In Nov we will likely know which drug maintains normalized serum K levels the best .
I'm betting on 10gms of ZS-9.
No one IMHO will consider partnering with RLYP until they see some long term data from ZSPH
Hard to see why you are so gun ho on AERI
Rocket failed ...in addition 35% of patients had eye redness ( mostly mild )
ITEK by comparison ...Trabodenson did not affect eye redness and reduced IOP by 7 mn at 28 days vrs Rhopressa reductions of 5.7 to 6.2 mn
ITEK 's Tradodenson appears the better drug ...more efficacy , fewer side effect . Why would they want to merger with AERI . After this financing round they certainly won't need the cash ?
chao You say you are an MD and I'm prepared to accept that on face value .
So I'll pass along the following and you can decide for yourself.
Jerry Isascson PHD at Life Sci Capital did a survey of Cardiologists treating HK ( Hyperkalemia ) in the Cardiology setting ...May 2015 .. In that report he estimated the cost of ZS-9 to be about $600 a month .
As you probably know , about 20% of the patients on RASS inhibitors have serum potassium levels above 5....and this limits the use of these RASS inhibitors even tho large Outcome studies have shown the use of RASS inhibitors reduce morbidity , mortality and progression of disease in patients with heart failure and kidney disease........so its a huge market for either Patriomer , ZS-9 or both .
Now Life Sci receives $ from ZSPH , just as Oppy receives banking fees from RLYP ...so take with a grain of salt from both Co's
Not sure if you are aware of the dosing loads between Patiromer and ZS-9. ZS-9 is probably going to be 10gms once a day for 90% of those on it .
Patiromer , to begin with , is twice a day for a total of 35 gms (including the 10gms of sorbitol , xanthan gum, and 4 gms of calcium ...for the moderate to severe HK patient .
Any idea what 35 gms a day ...or 7 packets of Patiromer , might cost each day for the moderate / sever patient . Its expected to be about 5 packets a day for the mild /moderate patient based on P 3 data.
Cost matters . Let me know if you find anything on the cost per month for Patiromer.
Bronson Its Form S-1 filed 5.32 pm ET on 7/31 ...Its on both my Schwab abd Fidelity accounts
The funding provides them with cash for 24 mths ..covers the cost of the P 3 trial . a long term safety data trial , new small trials in Trabodenoson 's neuro protective ability and the FDA NDA application if P 3 is great.
By the way I think the $20m note had to be convert to stock before they could do this financing. Notes usually come with conavents that limit a Co's ability to partner or raise funds.
The thing about their drug is that its a new method of action with fewer side effects then the existing drugs but can also be combined with the existing drugs to increase efficacy
Agree with risk of bias...applies to all of us
Re Spouses feedback limited in scope ....really ? She deals with insurance Co's , stage 4 CKD and dialysis patients , Nephrologists and Fellows on a daily basis Mon-Fri ( and some times half of Sat ).
Her view ...ZS-9 at 10gm dose is the most promising drug for hyperkalemia in decades.
Only " Promising " because we do not have long term safety and K level maintanence data yet .
From memory ZS-9 is about $600 a month . A concern with Patiromer may be the dosing load BUT it will immediately replace Kayexelate on approval and launch.
Full disclosure ...I sold my position in RLYP . I'm betting that ZS-9 will eventually dominate this market
Reading your earlier posts it looked as tho you had sold your position in ITEK
At what price pt would you buy back in ?
Agree with your view on the potential and on previous comments you made on ONCE
Chao well always good to read the views of a physician .
ZSPH is about 10 mths away from their PDUFA date . Plenty of time to name the drug and ramp up production. For the NDA to be accepted , production facilities would already have had to meet FDA specs.
Re my expertise ...limited to what my wife tells me ( Physicians assistant at a dialysis center , did CKD research at Yale ) and the feedback I get from the Nephrologists she works with. Plus the almost nightly case history report I get ...whether I want to hear it or not ...on some patient with a block fistulla, or uremic prunitus , or protein wasting and the occaisional case of hyperkalemia.
All issues which I assume you have intimate experience with.
Patiromer will be a welcome advance over Kayexelate ( which my wife's patient hate ) but once ZS-9 is approved Nephrologists will prescribe the drug that works the fastest , has the fewest adverse events / best safety profile and maintains the correct K level the best .
chao ...your first post ...welcome
Some long term data will be available on ZS-9 late Nov 2015 . Then we will get an idea if ZS-9 maintains lower K ( Potassium ) levels , better then Patiromer over 12 mths .
I'm betting ZS-9 does better
Re ZSPH announcing employee and or manufacturing ramp ?...why do they need to do that .
FDA ..PDUFA is May 26 2016 ..plenty of time .
Patiromer will dominate until ZS-9 is approved so expect a lot of positive publicity from Cramer et al about this new advance in treating hyperkalemia ...but the market is forward looking . Stock price trends will tell you which of the 2 will likely dominate
They are going to raise about $56 m......so thats selling roughly 4m plus shares at around $13 a share.
This funding covers them for 24 mths ...thru P3 , a safety outcome study the FDA would want with approval , and the whole FDA approval process ( assuming P 3 is a great success ).
The Co only had cash on hand to last to mid 2016 .....so would have had to either raise cash or partner by year end 2015 to run their P 3 thru 2016
The FDA approved a 5 arm p 3 trial ...good for the Co but 1300 patients to be recruited I believe , so the costs run up..
Anyway this places the Co in a very strong position .
If you believe in the drug and the market potential and are a long term investor , you knew that a capital raise or partnering was inevitable
From the New England Journal of Medicine April 16th 2015
" Sodium Zirconium Cyclosilicate for Urgent Care of Severe Hyperkalemia "
Report on subgroup of patients with severe hyperkalemia
" The mean serum potassium level at baseline was 6.3.
After one 10gm dose of ZS-9 serum potassium declined as follows
By .4mmol at 1 hr
By .6 mmol at 2 hrs
By .7 mmol at 4 hrs
The median time to serum potassium level that was less than 6.0 mmol was 1.07 hrs
These findings suggest that ZS-9 may be a therapeutic option in the urgent treatment of patients with severe hyperkalemia "
IMHO ZS-9 is an option in Acute care . Patiromer is not because of its slow on set of action .
Once the patient has used ZS-9 in Acute care , I'm betting that patient will stay on ZS-9 for Chronic care and also for those on RASS inhibitors .
Golong . You know I respect your analysis. You have been right on re CEMP.
However with Hyperkalemia I think you have a blind spot..
In my wife's clinic any Potassium level of 6 and above is considered Acute , patient is put on an EKG monitor and if the monitor shows irregularities , immediate attention is required ...acute medical intervention and possibly emergency dialysis.
The aim is to drop the serum Potassium level as fast as possible. So whether it takes 2 hrs or 24 hrs is a big deal. Nephrologists will use the drug that acts the fastest with hopefully the fewest side effects.
Insulin is a temporary fix
You might also chk National Kidney Foundation " Clinical Update on Hyperkalemia "
Aumas and paperprohet .
Actually I'll take the other side ...
I read the 10Q re the 2020 Convertible note . This note had several restrictions which gave the note holders quite a lot of control over the Company .
With that note now gone, the company will freely be able to partner with a larger Co to insure financial backing thru to late 2016 data. As it stands now the Co does not have $ to get thru to late 2016 data read out.
I think there is more to this then you realize . Note holders often have short position against their holdings...so that no matter whether the stock goes up or down they maintain a neutral position and collect their 5% interest..
The FDA allowing them to use a placebo in the trial and agreeing to a 5 arm superiority trial was perhaps the real game changer here after all . I can see big pharma being interested in a stake in that . To clear the way the Note holders would cover any short position they had and convert their note to stock..
So I think the decks are being cleared here to enable a partnership / backing deal with a larger Co....because of the neuro protective / glaucoma relief potential their drug has and the trial design approved by the FDA.
I only have a small position , but would be buying , not selling here