Most community docs I know (many seeing > 100 MS patients) would like Tysabri back and will be using it as mono.
Most of us felt that the SENTINEL study should have been 3 arms. As I am not planning on using Ty plus Av in many patients (or should I say in any patient), I don't really care what the combo data is at this point. Some I know feel that the combo is better because the result were compared to actively treated patients and not placebo. They may be tempted to try combo with trepidation. Some feel very strongly (more in academics than in community) that combo is stronger and might use combo earlier. I heard one very prominent MS doc say something like "Avonex alone reduces relapses bt 30% and Ty/AV was 54% better than Av alone so that makes combo 84% better than placebo vs 66% in AFFIRM". Not very bright as using this line of thinking should be 30% plus 54% of remaining 70% or 67% (30 + 37)...where have we seen numbers like that before..oh yes AFFIRM 66%? I feel that they were avonex failures so the additive effect would be far less-- the 67% sounds about right.
This is our best case scenario...a free pass for both drugs. It gives JM "cover" may extend the A franchise for a while but will clearly set up TY as a MONO therapy.
We WILL find out sometime thi year.
If indeed PML was the result of "external factors", than TY and Avonex combo may still be used. I doubt however that too many neuro's will risk prescribing combo when mono is as or more effective and has no history of PML.
Confirmation of everything we already knew and then some:
1. 3 PML patients all had a commonality - all on other immunomodulators or immunosuppressants. "The mystery has now been removed and is providing the platform for FDA dialogue".
2. Discussions, review and analysis with FDA has been ongoing (told you they weren't "huddled" in their offices waiting for completion of the evaluations")
3. Mitigation of risk utilizing a combination of tools i.e. MRI, labtests and all is being discussed with the FDA.
4. ACUTELY aware of MS patients' HUGE unmet medical need - FDA, Biib & ELN are discussing "washout period" for concombitant therapies, reviewing data as it comes in and having ongoing dialogue and analysis in an effort to start MS 1808, Phase IV study as soon as possible to avoid potential relapses at the 6 month period.
5. With regard to the timetable - in discussions on an ongoing basis to achieve final agreement.
6. Not only is Elan & BIIB having ongoing dialogue with FDA but with Europe as well.
7. Statement made that "Data available in the near future" and again FDA & EU will be involved in the process concurrently.
8. Independent safety committee continuously monitoring data as it comes in.
9. Currently in discussions with FDA regarding protocol amendments for resumption of trials.
10. (Really interesting comment) "Have not made a decision about whether trial resumption will be only mono" (possible resumption of combo trial ... hmmmm)
11. Blood samples taken from study patients will provide a fantastic pool for the study of PML and the JC virus. (knowledge is power)
12. Meaning of completion of safety review is - (3 parts) 1-gathering of data 2-analysis of data 3-review,discussion & analysis with FDA. So completion of safety review will need to be done before the resumption of Phase IV which means August/Sept. at latest imo (based on 6 month period).
13. AD trials moving forward.
14. Prialt reimbursement issues getting some resolution = increase in sales.
15. Encore - Crohns trial - endpoints met.
I AM ELATED, OPTIMISTIC, HAPPY.....OUR TIME IS COMING AND SOON!!!!!
Great post. Thanks a lot for your summary of the CC.
I believe it is safe to assume that "patients 4 and 5" are not PML.
If 1808 allows combo, it would be interesting to see how many patients do that instead of mono. There will need to be a new amended protocol and informed consent form as the study has major material changes. I would spend a full hour on that Informed consent discussion stating multiple times "participation is voluntary".....
There is no clear reason for today's dip. Just trading.
Thanks, good post.
Most interesting is item 10, perhaps continue with combo trial. I mentioned this possibility last week here, as:
1. The evidence to date supports a conclusion of immunosuppression generally, not necessary due to a specific interation of the mono or the combo on the immune system;
2. No evidence to date supports a conclusion that the combo risk was anything more than broad immumosuppression of the immune system, i.e., it is not due to a specific action on the immune system that renders is suppress specific to the JCV virus (PML).
If they propose continuing the combo, I know a lot of longs here will bitch, but that is the best possible scenario for ELN and ELN commons stock. Even the analysts might realize that the risk assessment showed essentially nothing unusual or out-of-the ordinary (broad immunosuppression, just like when the system drops in AIDS).
Terrific post...... But you missed the best part(Not that you din't hear it.....your post simply took as a given) ..... they are moving forward to resumption CT of existing populations of Tysabri trials patients post haste.
How wonderful is that?
.... the rest of this stuff is just noise