Hi
I am thinking of buying some of this ....
Below is a SEVERE EDIT of what G.R. Chambers
wrote in a comparison of E vs N (I can't spell)
(the actual links are included)
Note:This is the author
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GekkoWire is written by Mr. G.R. Chambers who is currently employed as an Economist (I wanted to list my current employer here, but they requested I take it down). Prior to this position, Mr. Chambers worked in the Health Care Industry as a researcher for a DC public affairs firm. Mr. Chambers is a Cum Laude graduate of The University of Maryland, College Park where he majored with departmental honors in Economics and Finance, he also holds a minor in Accounting.
gekkowire.com
In summary - the comparisons presented look good to me
but I don't know if they are really APPLES to APPLES
gekkowire.com
This individual writes about HEB/Ampligen(sp?) and
though I didn't read it - scares me.
Page One
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gekkowire.com
The General AntiBody classifications:
Chimeric antibodies: 33% Mouse and 66% human
Humanized antibodies: 10-5% mouse and 90-95% human
Fully human antibodies: 100% human
The big selling point behind Nimotuzumab is the lack of rash and skin side-effects that its competitor Erbitux displays– which happens to be a Chimeric Antibody (NEJM article here).
Page Two
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gekkowire.com
First, Cetuximab is a chimeric antibody while Nimotuzumab is a humanized antibody.
In simple terms, Nimotuzumab contains less mouse parts than Cetuximab.
Second, they both affect the EGF receptor in slightly different ways, and this where the major difference occurs.
Cetuximab is a chimeric antibody
Nimotuzumab is a humanized antibody
It should be noted however, that there has been great debate about this issue though, some scientists have argued that there is really not that much difference between chimeric, human, and the fully human antibodies (article here).
131.111.9.218
And that the different results from the drugs may perhaps be attributed to other reasons.
Nimotuzumab Vs. Erbitux Phase II
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
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Ok, so how does Nimotuzumab compare in a similar trial?
Well this comparison is tough, because if you will note that in the Erbitux phase II trial, Erbitux was given as a single agent therapy for patients that are platinum-refractory, and I was unable to locate a trial in SCCHN patients that were treated in a single agent therapy with Nimotuzumab.
So I don’t have a direct comparison trial for the Erbitux Phase II data.
There was however, a comparison trial done with Nomituzumab and Erbitux, but you see Nimotuzumab was compared to Erbitux in combination with radiation therapy so it is still not useful as guaging results for the phase II data from the Erbitux EMR-016 trial.
However in the comparator trial Nimotuzumab showed less toxicity and and similar efficacy to Erbitux (Poster here), which we will discuss in the next post that contains the Phase III data.
But what I would want to see is how Nimotuzumab performs in patients receiving the same therapy as in EMR-016 Erbitux trial, because that is one of the phase II trials that helped get Erbitux approved.
gekkowire.com
Page Three
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gekkowire.com
Nimotuzumab + Radiation Therapy Vs. Cetuximab + Radiation Therapy the IMCL-9815 Study
So we have a side by side comparison, I’m going to list the appropriate data so our readers can have a firm grasp on what I’m talking about. The cetuximab data (data sheet here) is extracted from a journal article titled “Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck,” which was published back in 2006 (article here) and the Nimotuzumab data is being taken from the 2009 ASCO poster (here).
Nimotuzumab+Radiation Cetuximab+Radiation
Overall
Response Rate
ORR = CR + PR) (%) 76% 74%
Median Progression
Free Survival
(Months) 20.71 17.1
Percentage increase
in acneiform 0% 16%
rash over standard
Radiation Therapy Grade 3-5
Percentage increase in
acneiform Not Given 77%
rash over standard
Radiation Therapy All grades
Alright let’s sift through the data. First, it is good to gauge the health that the patients are in during the two trials, which unfortunately we can’t do because YM doesn’t give the KPS score for the Radiation therapy arm of the trial.
What we do have though is some good comparison data on toxicities. According to the NEJM article’s toxicity data sheet (posted here) the amount of serious acneiform rash toxicities at a grade 3-5 (or serious level) that results from taking cetuximab increases 16% over standarad radiation therapy, and if you account for all acneiform rashes (even minor cases) the number when taking cetuximab plus radiation therapy increases 77%.
So when we talk about skin rashes were, we aren’t talking small potatoes here.
Nimotuzumab on the otherhand, showed no additional serious acneiform rashes when taken. The only real problem that I have with YM’s data is that they excluded from the write-up the amount of all grade acneiform rashes that occured, minor or not.
This would have been a great way to differentiate themselves completely from Cetuximab.
Finally, the increase in median progression free survival and the comparativeness of the overall response rate would seem to indicate that Nimotuzumab has a slight edge over Cetuximab when increasing patient survival.
What should be kept in mind though is that there is a couple of years difference between the two studies, so technological advances in medical equipment could possibly account for the increased OR and PFS in Nimotuzumab patients. Tomorrow I’ll follow up with the weekly Pharma recap and the comparison of the Nimotuzumab data with chemoradiation Therapy. If you liked this article click on some ads.
Page Four
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gekkowire.com
Let’s start with the data, YM Biosciences is again comparing Nimotuzumab to data collected during an already completed Phase II pilot study for Cetuximab. The Cetuximab study that YM is using as a comparator trial was cut short due to serious adverse events. Two patients died in that study and there were multiple other serious verse events. The study was published in the Journal of Clinical Oncology and it can be found here. The data I am referring to for the Nimotuzumab trial can be found here. Below you will find a comparator data chart that I made so we can directly compare the data released by YM and the data in the Erbitux study in patients taking either Cetuximab and chemoradiation or Nimotuzumab and Chemoradiation therapies, after that I will run through a brief analysis of the data.
Nimotuzumab + ChemoRadiation Cetuximab + ChemoRadiation
Patients 22 20
Overall Response Rate
(ORR = CR + PR) (%) 100% 94%
Median Progression Free
Survival (Months) N.R. N.R.
Percentage Dermatologic 0% 23%
Toxicities Grade 3-5
Percentage Dermatologic Not given 95.2%
Toxicities all Grades
Patient Deaths 0% 1%
Median KPS 80 90
Cancer Stage (%)
III 13 % 14%
IV 87 % 86%
Like our last analysis, let’s run through the data. First, we want to take a look at the patient population. For those of you who aren’t familiar with the KARNOFSKY scale (labeled KPS in the data), it would be helpful to familiarize yourself with it (the definitions can be found here). In a nutshell, it is a gauge of the patient population’s overall health, the higher the score the healthier the person. So the first piece of data that sticks out to me is that the patients in the Cetuximab and Chemoradiation therapy trial were healthier than the patients in the Nimotuzumab trial. Patients in the Cetuximab trial had a KPS of 90, while patients in the Nimotuzumab trial only had a media KPS of 80. Why is this important? Because if you remember I said that the Cetuximab trial was closed because of adverse events and patient deaths. So here we have a pretty startling revelation, Cetuximab had healthier patients and far more toxicity issues than that of the Nimotuzumab trial. In fact, the Cetuximab trial with chemoradiation was so toxic they had to shut it down. Even more, take a look at the serious skin toxicities in the Cetuximab trial, 23% of patients had serious skin toxicity of grade 3 or higher (I attached the toxicity data here). In case you are not familiar with how severe a grade 3 toxicity is I have attached a chart here that shows the different grades for different body parts. If you’ll note for the skin (you’ll have to scroll to the bottom of the page), to have a grade 3 event you must basically have to have open rashes somewhere on the body for it to be reported. And when you include all skin toxicity events in the Cetuximab trial the number moves up to 95%. On the other hand Nimotuzumab reported no increase in Grade 3/4 toxicities on the skin. Now, here is the portion that is of minor concern to me though, in YM Bioscience’s data they didn’t specifically give the lower grade skin toxicity numbers that I would have liked to have seen. In other words, I would have liked to have known the minor events as well, but alas the data does not seem to be available.
Now here is the real kicker for me, the overall response rate in Nimotuzumab’s trial is 100% and that is slightly higher than the Cetuximab trial’s 94%. Granted it is only 6% higher, but I would encourage my readers to take a quick glance at the data reported in Cetuximab trial’s journal article, because even the journal states that there are data issues with their overall response rates. It reads “Of the 16 patients assessable for response, 15 had a major response (two CRs and 13 PRs), and one patient had progression of disease, yielding a response rate of 94% (95% CI, 70% to 100%). In five of 13 patients, the PR was considered unconfirmed because only one radiographic evaluation, either at 4 to 6 or 12 to 16 weeks after therapy, was available for response assessment.” Did I read that correctly or did they just say that 5 of the patients included in the Cetuximab’s trial Overall Response Rate data can’t even be confirmed because they only did one follow-up evaluation. So in a sense we don’t actually have a clear picture of the Overall Response Rate in the Cetuximab trial. Furthermore, keep in mind that the patients in the Cetuximab trial were HEALTHIER to begin with and they have a lower overall response rate than in the Nimotuzumab trial. So in my opinion, Nimotuzumab has got Cetuximab beat at the current moment, of course more testing will be needed on the toxicity issues, but currently the data looks very promising. Tomorrow I will discuss the other indications and Nimotuzumab’s current orphan drug status for Glioma.
gekkowire.com
regards
John McCarthy |
