Tim Enns hinted at several things about Eortc trial. They may of increased cycles and lowered dosage...I hope they have this much flexibility in these trials. However if every stinkin anal yst is assuming a strict regimine similar to approved dosing and investigators leaned more towards additional cycles with lower dosing, well just maybe we will surprise everyone.
Now one more tibit, it was mentioned that this trial included only 5% of Int. one patients,(Going to look up how many of this population was in the approved trial), well in statistics as some of us took in college, if you want a favorable statistically result, you minimize what would drag you down. I'm sure Vidaza had some emphasis on which groups would hurt their stats. This is not cheating, because you are benefiting the group that's outside this classification and the standard care arm has the same breakdown on classification to measure against.
Plus, here's what maybe the most important point here. PHRM made reference a while ago that Dacogen showed less of a survival benefit then the 10 months in some trial. Well that could be influenced heavily, by how many of the Int. 1 patients that were in that trial. If it was loaded with a group that didn't benefit as well from Dacogen as other classifications it would influence the statistics. Hope I made sense here.
Wonder what percentage of Int. 1 patients were in the Vidaza survial trial?
<<What seems more likely (and I'll look into it when I get a chance) is that the designation would prevent a generic of the same drug for the time period - enhancing the profitability of all of the named drugs.>>
This is exactly the case. The drugs get a 10 year period of exclusivity instead of the usual 7. But we still get a contradiction here because after Vidaza has been metabolized in the body, it becomes decitabine aka Dacogen.
"What I don't understand is how they can assign orphan status to two drugs treating the same condition."
Conversely, why wouldn't you allow any effective treatment in any indication?
I mean, the time period they are talking about is 10 years - there is no way the intention would be to keep out new or better drugs for that time period, or to discourage the development of them.
What seems more likely (and I'll look into it when I get a chance) is that the designation would prevent a generic of the same drug for the time period - enhancing the profitability of all of the named drugs.
Otherwise, the designation would need some kind of a challenge procedure to replace any named drug if and when superior alternatives are available.
In this case, both Dac and Vid are already named for AML at least.
<<what has never been explained with all this Orphan status is how it could apply in MDS at all - MDS is not a rare "orphan disease", while some of the secondary uses may be.>>
From your posting, it states, "The orphan drug designation was established by the EMEA to encourage the development of treatments for rare, life threatening medical conditions that affect fewer than five in 10,000 people in the European Union (EU)."
5 in 10000 equals .05%. I don't know the exact number, but assuming a population of 500,000,000 for the EU that would be 250,000. I believe the total number of MDS patients in the EU is well below that number.
What I don't understand is how they can assign orphan status to two drugs treating the same condition.
Dacogen has also been granted Orphan drug status -
what has never been explained with all this Orphan status is how it could apply in MDS at all - MDS is not a rare "orphan disease", while some of the secondary uses may be.
"Dacogen(TM) (Decitabine) For Injection Receives European Orphan Drug Designation for Patients With AML <br><br>MINNEAPOLIS, Aug 01, 2006 (BUSINESS WIRE) -- MGI PHARMA, INC. (Nasdaq: MOGN), a biopharmaceutical company focused in oncology and acute care, today announced that the European Medicines Agency (EMEA) has granted Dacogen(TM) (decitabine) for Injection orphan designation for the indication of acute myeloid leukemia (AML). Dacogen was approved by the U.S. Food and Drug Administration (FDA) on May 2, 2006 for the treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2, and High-Risk International Prognostic Scoring System (IPSS) groups.<br>The orphan drug designation was established by the EMEA to encourage the development of treatments for rare, life threatening medical conditions that affect fewer than five in 10,000 people in the European Union (EU). This designation may also provide 10 years of market exclusivity in the EU following marketing approval. Dacogen was previously designated as an orphan drug by the EMEA for the MDS indication.<br><br>Dacogen is being co-developed by MGI PHARMA and Janssen-Cilag, a Johnson & Johnson company. Janssen-Cilag companies are responsible for regulatory and commercial activities in all territories outside North America, while MGI PHARMA retains responsibility for all activities in the United States, Canada and Mexico."
Tron thanks for the link a great report. So much for the analsyts not doing their homework. To paraphrase Gale Sayers, "When you hit your knees tonight pray for MP 470 and decent EORTC survival data. Would not like to wait another 5 years to see a properly designed trial.
Well I have to agree with Batzem. Just read this report and it's an eye opener and would of been useful, years ago. But they give Dacogen a 20% chance to beat the survival number and 30% chance it won't. The less cycles and capping the cycles at 8 will probably affect this trial. They did state that at 6 cycles at 6 wk intervals would be equal to average Vidaza 9 cycles.
Do the math:
6 cycles x 6 weeks = 36 weeks dacogen
9 cycles x 4 weeks = 36 weeks Vidaza
The earlier trials of Dacogen used 1-3 cycles and a lot of measuring survival is based against some patients only receiving one cycle in approved trial. We have to hope that because of potency that the benefits continue. But Manuso has stated that the longer in the blood stream the better these drugs work and we all know that these drugs only work for a short period. So additional cycles of vidaza may give it the advantage.
Why did Tim hint at some adjustment by investigators may of been made? Is this just more B/S by SUPG or could there be some truth to this. I just hope that maybe they saw that 8 cycles would add more benefits. This would help:
8 cycles x 6wks = 48 Weeks
Here's my dumb question and I want to make sure I thought this through correctly.
Vidaza showed a survival to 24 months which is 104 weeks, right? Well if they took this stuff for 36 weeks on average and lived some 68 weeks after this? What am I missing here. Am I looking at it wrong?
here is a link to the best "rationalization" analysis of the EORTC risks as I have found (from analysts at Leerink Swann)
I think they have motives to make EORTC look as bad as possible as part of a PHRM/CELG pump, but they have at least assembled a good deal of data to look at.
Also notice that for all of the EORTC results bashing, they make the point that they believe that Dacogen is as efficacious as Vidaza.
It seems to me, even with weak EORTC data, that both doctors and J&J will focus on the results as a product of bad trial design rather than any proof of ineffectiveness. The question is therefore - can J&J still apply with EORTC+Ph2 trial results, or do they need to wait for additional trial results.
With Vidaza as being a pro-drug of Dacogen, we are a long way from any theory that would suggest a scientific reason for one drug to be superior to the other - which is why even now, many doctors/researchers believe that Dacogen is the better drug - since it does not require metabolizing to work.
take a look at the report and post your observations.
>>Most MEDACorp consultants we spoke to were generally optimistic about the survival benefit of Dacogen and a positive outcome of the EORTC trial. Consultants generally view Dacogen and Vidaza to be equivalent in both efficacy and safety except for a small minority who view Dacogen to be more efficacious. There was a range of expectation on the relative strength of the survival benefit compared to the Vidaza AZA-001 trial. The majority of the physicians to whom we spoke believe that EORTC trial will show a survival outcome, but likely not as robust as that from the Vidaza AZA-001 trial. A small number of consultants anticipate a survival benefit on the same order of magnitude to the Vidaza findings due to their belief that Dacogen is a more potent agent.<<
>>A. Dacogen displays equivalent or better survival benefit in the EORTC trial to Vidaza in AZA-001 trial . We believe this is the least likely of the three scenarios and would assign a probability of approximately 20%. We believe the chances that Dacogen shows better survival benefit in the EORTC trial compared to Vidaza in AZA-001 trial are low due to limitations of the treatment duration as well as lack survival benefit in past trials. Under this scenario, assuming a positive Dacogen EORTC trial and an equivalent magnitude of survival benefit, we expect Vidaza and Dacogen to split the MDS market equally, with each drug receiving roughly 50% of the hypomethylating agent market.
B. The EORTC trial fails to show a survival benefit for Dacogen. We estimate a 30% probability for this to occur. Under this scenario, we assume a majority of physicians will switch patients to Vidaza, which will capture 90% of the hypomethylation agent market. Dacogen will capture the remaining 10% as some physicians continue to view the two agents to be equivalent.
C. The EORTC trial displays a magnitude of survival benefit but substantially less than Vidaza . We believe this is the scenario most likely to occur, with an approximately 50% probability. Under this scenario, we assume Vidaza captures 70% of the MDS market that is treated with hypomethylation agents and Dacogen captures the remaining 30%. We note that our financial model for Celgene assumes a 60% vs. 40% market share split for Vidaza vs. Dacogen. Therefore, our above analysis suggests that the outcome of the Dacogen EORTC trial will more than likely not generate upside to our current estimates of Vidaza.<<
That is the most comprehensive report I have seen to date on this subject. It also helps to explain much of the downside we have been seeing. But in the end, it still seems to be very self serving and should be discounted somewhat.
In scenario A, Dacogen is presumed to be either the same as or better than Vidaza and they give a market share split of 50/50 (effectively no change from what we are already seeing).
In scenario B, Dacogen fails to show a survival benefit and the market share split becomes 90% for Vidaza and 10% for Dacogen.
In scenario C the survival benefit for Dacogen is substantially less than Vidaza yet still measurable and they give Vidaza a 70% share.
Doesn't this seem like a bit of false logic?
They are lumping the "Dacogen is better" scenario in with the "Dacogen is equal" scenario and calling it A and they are implying that Vidaza's sales cannot be affected by the EORTC study. Shouldn't those two potential results be separated? If Dacogen has a better survival response shouldn't it get the 90% share that was awarded to Vidaza in scenario B?
The report is probably the most comprehensive analysis I have seen, but it fails to acknowledge the possibility that Dacogen could prove to be better. It was obviously contrived to justify owning PHRM over SUPG or MGI, and loses credibility as a result.
They also put current market share at 60% for Vidaza and 40% for Dacogen. This is not completely accurate, and lends itself to more lost credibility.
BTW, tron, thanks for the link
From what I can see free. In the approved trial 28% of the 89 patients were Int. 1 and in the control arm 24%. Just maybe Tim threw us a bone on something important, statistically? This can maybe give us some comfort and I doubt any anal-yst would look this close to breakdowns and even have a understanding on previous trials survival stat's. BTW we have to compete with 9.4M survival benefit, not 10M.