The two trials address two unrelated issues. The most advance ongoing trial addresses anemia in the NDD-CKD patient population. The most recently initiated trial addresses the importance (or lack thereof) of normalizing phosphate and blood levels in CKD patients prior to advancing to the dialysis stage and whether or not this can impact the long term benefits of dialysis (Of note, this trial was not initiated by Keryx).
It is rare (though not unheard of) that a company will generate two identical P3 trials unless prompted by the FDA after submission for approval, that an additional trial with additional data is necessary. Even in this case, the follow-up trial will have probably been modified slightly to accommodate the concerns of the FDA that were raised during the review process.
So we are not talking about two Keryx P3 trials addressing the same question.
The prize was shared with two others, one is a friend of mine Bill Campbell. He and his colleague developed an entire new class of drugs to treat intestinal parasitic worms. Putting things into perspective, in 2013 there were about 200 million cases of malaria world wide. At present, nearly 50% of the world population is infected with intestinal worms....this does not even include the use of the avermectins against livestock parasites.
No one can punch up a ticker on a computer and within 15 seconds generate an educated opinion and suggestion with any validity. If they could, they certainly would not be wasting their time on a stock show.
The sad part is that pseudo-investors really act on these opinions/recommendations. I am not saying his opinion/recommendation on RMTI is right or wrong...I am saying it is a fly-by-night approach and should be evaluated for what it is. Flip a coin. choose heads or tails and you will be right 50% of the time. His choices probably fair no better and probably worse.
Well, whether or not the patients independently decided to pursue checkpoint inhibitors, it cannot be looked at as something that is sanctioned by the FDA as a true clinical trial...not at this point. One or two patients would not be enough to make an evaluation of combination therapy. You might have to provide the link again on the slide show; however, unless it was indicated in the slide, or in an earlier slide providing the experimental protocol, which most presentations of this sort do, you should assume that the data presented relate directly to the DCVax trial and not to studies after the fact, nor including information parlaying CI with DCVax. I would like to qualify that this is my opinion and should not be viewed as dogma.
We have already hashed this through. This is a the patent application....not the patent. It probably has years to go before a decision will be rendered.
Makes more sense. In the past, it was hard to even get a response from the USPTO in 6 months...they are terribly backlogged; 36 months for approval is good if one has few glitches.
My understanding is when one refers to the "coordination complex" this is how the EU visualizes their NCE. They look at the entire molecule. However, the active moiety in ferric citrate, regardless of the formulation is Fe3+....that is what binds to transferrin and not the coordination complex. The citrate has no role in biofunctionality only bioavailability. In contrast, if Fe3+ remained irreversibly bound to the citrate, the Fe3+ would not work...it must dissociate completely to be biologically available; hence Fe3+ is the "active moiety". The Fe3+ bound to transferrin and any other target molecules, remains untethered Fe3+; no enhancement of surface area and not part of a coordination complex.
Now, if in fact the formulation of Fe3+ when bound to iron binding sites is different, than this has a shot. But if this was the case, the name would not be Fe3+. Scientifically, it would be given a different name more suitable to its chemical description i.e. Fe3+ triple hydrate???.
Anyway, that is my take....#1 Active is in the sense of binding. Put another way, when bound, the Fe3+ from Auryxia is no different than the Fe3+ from ferric pyrophosphate citrate. If I am correct, I do not see how the FDA can approve an NCE. I think this is the same reason why Keryx indicated many times that it was not essential to have the NCE...firing a shot across the bow and softening the blow early on.
Jeremy, upon some superficial background reading, the definition of a NCE in Europe seems to apply to the entire compound. The definition of NCE in the US applies (or so they have indicated) to the active moiety within the compound. These are completely different beasts that could easily differentiate the compound depending on which agency evaluated the submission.
Based upon the FDA's definition, it is my opinion that Fe3+ is the active moiety regardless of how it is presented to the body. If I am correct, the NCE will not be awarded in the US. In the EU, they evaluated the entire molecule. Given the changes that were made to the parent ferric citrate to enhance the solubility and purity of Auryxia, the EU saw this as an NCE; this makes sense. However that which binds to transferrin remains Fe3+ not Auryxia. The use of Fe3+ as a food additive in the US is well documented in the form of ferric pyrophosphate citrate, just another soluble form of Fe3+. The active moieties in Auryxia and in ferric pyrophosphate citrate are both Fe3+. Anyway, that is the way I see it based upon the information currently available.
JMHO for what it is worth.
I noted this below and continue asking for the patent serial no ...not the application serial no.
Be that as it may, I do not think the data is available to support the claims. I guess we will see in a few years when the a final decision is rendered.
Can you please provide me the patent serial number and not the application serial number? I have not been able to locate it.
Flipper...couple of things:
1) Combination patents date back a long way (1990s +). As per the claims, this may turn out to be difficult to defend...they are claiming everything under the sun.
2) More importantly, the best I can glean from my investigations is that the patent has NOT been approved nor issued; only the application. The application has been assigned an application number and an application serial number; however, unless others have been successful, I have not been able to find the patent when searching the USPTO website using either of the numbers listed above.
3) Third, and referencing comment #2 above, and referencing my limited experience with the US Patent office (I hold 8 scientific patents), I find it nearly impossible that a patent can be submitted, reviewed and acted upon within 11 months. It goes without saying, the first submission comes back loaded with claim rejections to which the submitter must respond. Is it possible? I guess anything is possible!! Is it likely? Nope!! So before jumping ahead too much, can you show that I am wrong and provide us a searchable patent serial number and not an application serial number?? I have yet to be able to locate one.
4) Finally, it is not difficult to patent when the data are available to support the claims; however, Drummond may wish to chime in on the issue of obviousness. Namely, as a concept, is it "obvious to one skilled in the art" to combine CPI and dendritic cell therapy? H3ll, even posters on this board have raised the idea of combining the therapies. So in essence, there is nothing new here. There is nothing that is not a logical progression of the science. If they had data to support the claims, then it is a bit different. But as an "idea" it becomes difficult to support as unique and patentable.....now that is JMHO
Don't misunderstand me. I think that the anemia label is much more important than the hyperphosphatemia label at this stage. I assume that any doctor who treats CKD patients off label for hyperphosphatemia will consider Auryxia. The anemia tag will provide an in to expanding treatment beyond CKD and ESRD. That being said, many still believe that the current P3 trial is for hyperphosphatemia. My comment was more for clarification on this issue than anything else.
There is yet another trial that has surfaced. The trial is not originating from Keryx though Keryx is a collaborator. The primary endpoint is a bit of a mystery to me:
"Primary Outcome Measures:
•Serum phosphate value prior to starting renal replacement therapy"...What the heck does that mean?
The secondary measures are equally nebulous,
"Secondary Outcome Measures:
•Serum hemoglobin prior to starting renal replacement therapy
•Serum transferrin saturation prior to starting renal replacement therapy
•Serum fibroblast growth factor 23 prior to starting renal replacement therapy
By definition, and if I understand correctly, all patients should reach the same endpoints prior to renal replacement therapy (dialysis) otherwise dialysis would not be required.
everyone is entitled to their opinion....even you!!!
As for slander, he has nothing to slander.
One more thing...if you believe there is a small market...so be it. What's the big deal? You are entitled to your opinion. I have no beef with that.
My point is that these patients are in a sorry way and anything the Nephrologist can place in their arsenal to help them feel better and maintain as normal life as possible, they will. Triferic, whether or not you choose to accept it, will fit that bill. The level of use is a black hole for everyone...you included....it always is on new products. The rest is quibble over "...you say potato I say potawto..."
You asked questions. I answered the questions as I understood them. I neither pumped nor bashed.
That being said, your thesis and conclusion that 'Triferic is not a substitute for EPO' does not constitute classifying the drug as a failure. You are "admiral-Keryx" so I assume that you have a predilection for the benefits of Auryxia over RMTI. Of note, Auryxia also is not a substitute for EPO. Its benefits fall in the same class as Triferic; they both treat iron-based anemia; the timing, administration and expected benefits differ.
Also the "production of hemoglobin" involves the binding of iron. Without the iron, you do not have hemoglobin; merely a collection of proteins. So EPO increases the production of those proteins but does not de novo assemble them; it requires iron as the binding force for the assembly of Hb. Point is, you cannot have one (hemoglobin) without the other (iron). You will notice as you read, the best way to increase Hb levels is to increase iron levels, because iron is the limiting factor in the production of Hb. The body does this to reduce essential ingredients i.e. iron, for bacterial growth floating around in your blood. Also, you cannot separate good iron levels from a healthy immune system. Iron does so much more for your body than just act to assemble Hb. Those taking Triferic will benefit in other ways.
There are several issues related to triferic that you failed to mention. One, RMTI already has a well entrenched position with dialysis centers and already has products that the end users trust and use. Buying new products from trusted suppliers is a big deal in this industry. Second, there is no new intervention for these patients. They will never know they are being treated. Finally, and I mentioned this above, although Triferic does not replace the use of EPO, it nonetheless maximizes the functionality of the Hb precursos already in the system.
Please evaluate and tell me where my facts are questionable.
1. Auryxia and Triferic do NOT compete.
A was developed to address hyperphosphatemia and iron deficiency in ESRD patients; Triferic was designed to address iron deficiency brought on by dialysis. Let the Nephrologist decide if they will be given synchronically or not.
2. A dialysis patient on Triferic WILL require IV iron at some point.
This is likely the case. Triferic was not developed to address iron deficiency brought on by ESRD; however, use of Triferic will likely prolong the period of time between alternative iron intervention and reduce EPO treatments.....but not eliminate them as the disease progresses.
3. Anemia is caused by two things--lack of sufficient red blood cells and/or the lack of sufficient iron in the red blood cells.
An oversimplification...the body can also destroys red blood cells. But in essence, anemia is cause by low levels of iron or low levels of blood cells.
4. For anemia caused by insuffieient red blood cells, .Epogen is given to stimulate the production of red blood cells.
Well yes and no. Red cells are produced, but there is no evidence that epogen improves fatigue or the quality of life in the patient. Once red cells are produced the increased hemoglobin that results still requires iron to function properly. Thus a patient is unlikely to " feel better" until the iron levels are restored along with the hemoglobin levels.
5. For anemia caused by insufficient iron, iron of some sort must be given. Iron is needed to help the red blood cells make hemoglobin, the stuff the carries oxygen to the cells of the body.
Not exactly. Only Fe2+ binds to hemoglobin efficiently. The cells produce hemoglobin (heme), iron binds in the center of the porphyrin ring. This is a large quaternary complex that in turn binds oxygen for transport. Not sure that "iron is needed for synthesis"; only functionality.
6.Therefore Triferic is NOT a substitute for Epogen.
No iron supplement substitutes for EPO; it maximizes the benefits
We are looking at two different trials. One active and not recruiting and the new one you refer to which is new. The trial in question (I was referring to) was initiated Sept 2014. The one you are looking at will not be completed until Sept 2017.
Title: A Phase 3 Study of KRX-0502 (Ferric Citrate) for the Treatment of Iron Deficiency Anemia in Adult Subjects With Non-Dialysis Dependent Chronic Kidney Disease
The endpoints for this trial are as follows:
Primary Outcome Measures:
•The between group comparison of the proportion of subjects achieving an increase in Hgb of ≥1.0 g/dL at any time point between baseline and the end of the 16-week Randomized period
Secondary Outcome Measures:
•Mean change in Hgb from baseline to end of the 16-week Randomized Period
•Mean change in TSAT from baseline to end of the 16-week Randomized Period
•Mean change in ferritin from baseline to end of the 16-week Randomized Period
•The difference in the proportion of subjects experiencing a sustained treatment effect on hgb
•Mean change in serum phosphate from baseline to end of the 16-week Randomized period
As noted in my previous comment, the only mention of hyperphosphatemia is in the final "secondary measure"
Remember, and everyone should take note of this. I continue to see misunderstandings as represented and implicated in your #8 above. The predialysis market as per the "new" label if approved, will be for anemia; Auryxia will not get a label for hyperphosphatemia and the treatment of NDD-CKD.
You do not have to take my word for it. Just read the trial guidelines on the clinicaltrials.gov site. Of the 5-6 primary and secondary endpoints listed, hyperphosphatemia is listed as the last of the secondary endpoints. So do not expect much as it relates to FDA approval and labeling for this indication.
If approved, you can expect the naysayers to dampen the enthusiasm by indicating that treatment for hyperphosphatemia was not approved for this patient population. Granted, off label use will ensue but I expect that this is ongoing. This is not my opinion, the FDA approved trial that is ongoing for this patient population is for anemia. Lets get this straight.
It certainly seems like the admiral posts with an agenda that is not in the best interests of the other board members. The confusing part is that I am not sure whose interests he has in mind. Some posters just wish to anger other board members...but as a scientist for 35 years, I usually take these comments with a grain of salt when they are opinion. However, when the facts are unsubstantiated or tainted substantially by opinion, it does tend to get under my skin.
I probably should take my own advice and simply not respond.