Read what I wrote...let me copy it for you since now you seem to have problems remembering, "...My personal opinion is that Keryx never submitted the NCE..." what of that phrase did you not understand. Where did I "...make a claim?" It is an opinion...oops I forgot, that word is too long for you to comprehend.
I may or may not drive a dodge...better than the tricycle you putt around on and you probably fall down riding it. That is common for people who are unbalanced...mentally and physically. You got "double whammied"
Also, learn to write in coherent sentences...maybe then and only then will someone (other than me) care what you write.
By the way, did you flunk out of Trump University???
First, please define your terms...who are " they" and "them"...Learn to write before you criticize others comments.
Second, you may call me a "soft basher" (whatever that may be) but please provide evidence that what I have said is incorrect regarding the definition of a new chemical entity. Do you even know what an NCE is? Have you ever research it? If you had, you would find that the definition I provided above was not made up. Also, please specifically state where I used facts to "spin" (whatever that means).
I just love people who shoot from the hip and ask questions later. If you cannot handle the facts then do not respond. But until you can demonstrate that what I said is incorrect or not factual (at least where I did not specifically state 'in my opinion'), then keep your comments to yourself. You are not "HILARIOUS"; rather, you are "SAD".
By the way, I still own 2K shares.
As per your statement below from the EU, "...The European Commission considered ferric citrate coordination complex a New Active Substance...", the EU views the entire compound i.e., ferric citrate coordination complex, for evaluation of an NCE. The US would look only to the Fe3+ portion because that is what is binding to the macromolecules in the body. Now, if the Fe3+ in Auryxia and not the entire ferric citrate coordination complex has been modified to enhance solubility, it would be a different issue. But to the best of my knowledge, the entire ferric citrate has been modified, and the Fe3+ when dissociated from this complex, remains unchanged.
An NCE is unrelated to patent issues. If the pre-dialysis (I assume you are relating this to treatment for anemia) indication for anemia was patented at the time of original submission, length will not be added to the patent portfolio. If, however, treatment for anemia was patented subsequent to hyperphosphatemia, the patent clock will start at that time. There are chemical patents for new compounds and and "use" patents that can extent protection for older compounds but only for that indication.
In general, one cannot link clinical trials to patents. The patents are generally sought for and obtained long before a company even thinks about conducting a clinical trial. By the time the trials have been completed and the drug approved, there is not much time left on the original patent.
The comment below by Pentech is unfortunately conjecture. There is no evidence that the definitions in the EU are the same as the US. Indeed there is more evidence that they are different. The EU seems to view the entire compound whereas the US views only that portion of the compound effecting the change. As example, in the EU if a brand new salt of Fe3+ were developed for treating hyperphosphatemia, they would be likely to approve based on their version of an NCE. In the US, however, that compound would be looked at and if it was deemed that when dissociated, the Fe3+ was still the portion to bind the target molecule and effect change, it would not be considered a "new entity" because the "active moiety" (per their definition) is the same regardless of the salt formation by which it was presented. The guidelines specifically state that "salts" of previously approved "active moieties" will not be considered. Ferric citrate has been around a long time.
That being said, the FDA has recently made changes to these guidelines that I have not yet read into.
My personal opinion is that Keryx never submitted the NCE.
It is not a patent issue. Regardless how it is purified or synthesized, the FDA looks at the "active moiety" within a compound to define whether or not it can qualify as an NCE. The active moiety is Fe3+ presented as ferric citrate. Ferric citrate is older than dirt albeit in non-purified format. Ferrous sulfate is comprised of Fe2+ which is substantially different than Fe3+. Ferrous sulfate in and of itself would not invalidate an NCE; however, any salts of Fe3+ would invalidate ferric citrate. So, I am not expecting anything material from the NCE.
Below is the data from a peer reviewed, scientific journal article that appeared in the Annals of Oncology and obtained from the NIH PubMed website: Of note: it is the same data as I cited above and the same as yours:
"Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. E. A. Mittendorf, G. T. Clifton, J. P. Holmes, E. Schneble, D. van Echo, S. Ponniah & G. E. Peoples
The figure summarizing the data is presented below:
As noted above at the conclusion of the study, p = 0.05 for the vaccinated vs control group and p = 0.11 for the optimally boosted group. Finally, this was copied directly from your website which by the way has the same figures as in the article:
"Finally, those patients who were optimally boosted demonstrated a trend toward increased DFS compared to CG (95.2% vs. 80.3%, p=0.11) (Figure 6)."
And by the way, for future reference, you obtained this information from a "poster" which is generally not peer reviewed. Data analysis can change at any time moving from a poster to publication in a peer reviewed journal.
It is likely our discrepancy is based on your analysis at 3 years and mine at the conclusion of the study
Though different sources, I think we are looking at the same charts. My source is indicated below:
Those charts indicate a p=0.05 value for the optimally dosed patients but more importantly, a p = 0.11 for the boosted patients. That scenario makes little sense if the treatment is working. Explain biologically why a treatment with a vaccine works better in patients given a primary immunization than in those given a boost? I neglected nothing in my comments. One must evaluate the whole picture not just pieces that suite an argument. Results from a primary immunization are of little meaning if they cannot be substantiated in patients given a secondary treatment.
Interesting question. Inasmuch as it is a single blinded test (patients only) the investigators (Roche) should be able to determine whether or not there is an effect. I suspect they are examining the data as we converse. If they see positive results to this point) they will continue. If not, they might abort. My guess is that they never tested this same patient sub-population (HER 1 and 2 only) with Herceptin, so they will continue the trial in the hope they will glean more information on Herceptin only...even if NeuVax fails.
I should have clarified; the 97+/- evaluated were in the treatment group. Be that as it may, the number you quote i.e."...78% RRR and 100% DFS in the small subset that was optimally dosed and boosted..." included 37 and 21 patients, respectively. The logic stands that this is far too small a group to make any meaningful assessment. But as I indicated above, the optimally boosted group was not statistically significant (p = .11) in the boosted group which should have sent up a red flag i.e. how could significance be achieved in the vaccinated group then break down in the boosted group?Either way, it remains meaningless with such a small group. Clearly there are other factors at work here that retrospectively sub-selecting on HER positivity levels alone did not account for.
No offense, court, but there is nothing that can be gleaned from this report that is positive; that which you deemed "impossible" actually happened. How do you know that when the larger trial was generated, NeuVax actually altered human biochemistry sufficiently in this subpopulation to adversely affect this treatment group. In the end, the controls responded as expected and the NeuVax subgroup responded more poorly than expected. A small trial where the data was cherry picked would not have revealed this.
Going back to the trial from which this trial was derived, it only had 97 participants with varying degrees of HER-2 positivity, and had no statistical significance. This was further reduced to 45 patients in a sub analysis when those with HER-2 protein positivity of 3+ were excluded. Some have stated that the results "approached significance" and this, in and of itself, is important. While this remains a contestable point even when the patient population is large, in a trial with only 97 patients it is hogwash. As you now know, there are reasons why these definitions for significance were developed. The only positive thing anyone can ever glean from PI and PII data is that the treatment has promise. Far more drugs in the cancer field fail PIII trials than pass. That is a statistic you should understand and adhere to.
The reality is that Gale should have conducted yet another less expensive PII trial rather than to "cherry picking" their PII data and build an argument for a PIII trial. They were running short of cash and decided to take some short cuts because everyone knew the results would be positive...everyone knew they had the best oncologists in the world...everyone knew they had the smartest scientists on the planet...yadda, yadda, yadda.
Don't waste time looking for answers. I can give you all the information you need right here...........it didn't work!!!
In my opinion, if the NeuVax data "suggested" benefit but without statistical significance, the trial would not have been terminated based on futility. The company evaluating the data would have let it go on the assumption that by the end of the trial, differences among treatment groups could have become more clear and the endpoints could have been achieved; they would not have pulled the plug if "tendencies" were seen in the positive direction.
However, I assume the reason the trial was terminated was because by this time in the trial, a delineation between treatment groups should have become apparent even if not yet reaching statistical significance. They likely saw absolutely no difference at all between treatment groups which in turn indicates that continuing the trial would have continued the current trend.
As for your question, "...how can NeuVax be such a disaster on its own, but yet work with Herceptin?" there are such things as synergistic effects which are not uncommon. This is where combining drugs generates a response greater than what would expect from the additive effect of both drugs combined. It is like adding 1 + 1 and getting 4. That being said, this is usually when both drugs generate a positive response independent of the other, which is not the case here.
Many smaller trials generate very good results because the population and diversity of patients is small. When the patient numbers are increased to include a more diverse population base, that is where the rubber meats the road. In this case when the patient numbers were expanded there was no statistically significant difference between the treatment groups. As such the PI and PII trials become moot. Further and if memory serves, this trial was not based upon the entire PII population but a subset of that population wherein the Company said, "look, the whole trial did not work but the treatment seems to have worked on a subgroup of the PII trial...So, lets generate a PIII trial based on looking only a that subpopulation."
The PIII data is what it is, it is evaluated independent of any PI and PII data, and it supersedes any PI and PII data.
Fast Track defines a relationship between a drug (any drug) and the severity of a disease as well as current treatments for a disease. FastTrack in no way signifies a relationship between the drug and success in obtaining approval for the drug. The two are not mutually exclusive.
With small biotecs there is always a level of trading in one company that an be directed by emotions in the industry. So you might expect NWBO trading to be subject to some of that emotion, especially since they are in similar lines of work i.e. cancer vaccines.
My point is, if you go to the GALE board you will see some of the same innuendo regarding "historical norms" when it comes to the trial length and misinterpreting these anecdotal data to imply positivity for NeuVax. This logic permeates nearly all boards looking to make sense of minute, ongoing trial information.
Each trial must stand on its own. The problem that NWBO is having with the FDA (in my opinion) is that the placebo group has dwindled by virtue of design of the trial which in turn weakens the integrity of the data on the treatment group. They need to reconcile this with the FDA before moving on. I hate to say it this way and I understand the potential implications, but NWBO would have been better not to generate a "crossover" group and stick to the original plan. In my opinion, this would have prevented this pseudo-halt in the trial.
It is difficult to use "historical OS" data because every trial is different. If you disagree, just look at the various DCVax trials, they vary tremendously with respect to the "Inclusion" and "Exclusion" criteria which means the subset of individuals in each trial is different. Collectively, historical norms may cluster around a specific endpoint I.e., OS for example, but as the data increase on historical norms, that does not mean that "pockets" of non-responders or over-responders cannot exist in the next trial based upon differences in inclusion/exclusion criteria. This is akin to your GPA while going to school; get an "F" in the first semester your freshman year and it completely blows your GPA...you're placed on academic probation. Get that same "F" in the last semester of your senior year and it barely puts a dent in your GPA. Further, the "F" in your senior year would not have been predicted by historical norms i.e. your GPA.
I noted before I was invested in a company testing a cancer drug. All the "expert modelers" and statisticians on the message board predicted that the XYZ event defining a positive outcome (based upon historical norms) had passed by months. I cautioned then, as I am cautioning today, not to focus on historical norms. That recommendation fell on deaf ears and of course I got labeled a "short." Well, the trial modelers were indeed correct; the treatment group lived a long time, but the placebo group unexpectedly lived much longer than expected and the trial was a bust; even amidst wonderful PI and PII data (check Keryx and perifosine). No one could explain why...it was totally unexpected, but "it was what it was." I learned my lesson about "historical data."
As for "DC Vax becomes clinically beneficial", the governing body involved in approval i.e., FDA, could give 2 shyts about clinically beneficial if the scientific data is insufficient to support the claims. The two are not mutually exclusive.
Anyway, JMHO...good luck
I think it was incorporated in my comments. It goes without saying that as Triferic goes so goes RMTI. Triferic will be (hopefully) the revenue drive going forward. All other products combined to date (not including Calcitriol) have not been able to generate a profit for the company. I am not expecting much improvement in the numbers from calcitriol except that overall volumes of all products may increase as "package" deals get established; again..."one-stop-shopping". That might be the saving grace. Hence, the future of this company (in my opinion) rests on Triferic penetration and sales. Don't look to Calcitriol as part of the larger equation.
It is hard to know what you mean by "business model". It is my understanding that RMTIs "business model" is in generating and selling products to treat ESRD, CKD, iron deficiency, and in general, hemodialysis. I am not expecting this to change once Triferic comes on line.
Further, and based upon arguments I have listed in other portions of this thread, I would venture to say that we have essentially one product coming on line. The market for Calcitriol is very competitive and not only with other producers of Calcitriol generics, but also paricalcitol (Zemplar), and doxercalciferol. So, the pricing structure will follow suit. The only positive is that even a small margin might help in that the marketing infrastructure is already in place so sales should be accretive; but minimally (in my opinion). The biggest benefit is in RMTI becoming a "one-stop-shop" as I mentioned above. It is possible that product volumes may increase because of this but there will be a cost and margins may get squeezed even further in the process; it is a wait and see game.
Not sure if that addresses your question.
You are missing the point. I never questioned or commented on whether or not triferic would or would not be successful. That has little bearing on the margins and sales projections for their current product line. Essentially, my comment was that I am expecting that Calcitriol will contribute minimally to the bottom line given that the current pricing structure on their other highly competitive products has not garnered profits to this point; Calcitriol will undoubtedly follow suit. I further noted that Triferic is the only saving grace for this product line; so on this we can agree. But you have to explain to me why the current, "... suite of products this company will have in short order will produce such momentum going into the future..." will automatically generate phenomenal earnings (absent Triferic) if they have not done so yet. This logic escapes me sand that was my point.
That being said, your thread is just laden with hypotheticals:
"...And if/when the other applications..." Light years into the future if at all
"...international growth..." I expect this is accounted for in your projections
"...price of $15 to $40..." hypotheticaal based upon your sales projections; time period was not defined.
"...but these are the facts..." you have provided only innuendo, no fact
One thing that we do not know is whether or not triferic will continue to be used or if insurances will continue to pay for it, after the patient migrates to IV iron. Make no mistake. the patient will migrate to alternative forms if iron repletion as the disease progresses. The company has mode no claims relatingTriferic and non-dialysis-based iron repletion.
Adapting Triferic to oral administration would be a big breakthrough. But that will take a long time to validate if at all. Still, we agree that Triferic will fill a void and will enter the ranks of treatments for dialysis-dependent CKD anemia.